Appendix A–Infertility Treatment Options

There are many infertility options available to you, including some that will preserve your genetic connection to your child. Not all options for infertility will work for all couples, which is why it’s important you consult with your fertility counselor and reproductive endocrinologist about which options are available for your particular situation.

In general, here are the several options for infertile couples available today:

FERTILITY DRUGS
Usually, the first infertility treatment that couples undergo is fertility medication. When a couple first has trouble conceiving naturally, their physician will usually prescribe them fertility drugs aimed at stimulating ovulation, thickening the uterine lining, increasing sperm count or other methods designed to increase the chances of conceiving. Talk to your reproductive endocrinologist to discover which fertility drugs might be right for your infertility options.

MEDICAL PROCEDURES FOR INFERTILITY
If fertility drugs do not enable a couple to conceive naturally, their reproductive endocrinologist or fertility counselor will usually suggest medical infertility options, otherwise known as assisted reproductive technology (ART). Again, which medical procedure will be best for you will depend upon your own situation, but here are some of the more common ways that conception is assisted medically:

In vitro fertilization (IVF): Perhaps the most commonly known ART method, in vitro fertilization involves the harvesting of sperm and egg cells from each partner. Then, the gametes are combined for conception in a laboratory dish. Once the embryo develops, it will be transferred into the woman’s uterus for implantation. After it successfully implants, her pregnancy will likely proceed just as any other pregnancy would.
Intrauterine insemination (IUI): If the harvesting of egg is not needed, a physician will usually recommend IUI. In this procedure, sperm is collected from the male partner, “washed” to remove seminal fluid and then inserted directly into the uterine cavity to increase chances of conception.

Intracytoplasmic sperm injection (ICSI): This treatment is the part of the IVF process where a single sperm is inserted into a retrieved egg. It’s usually used in cases of male infertility problems.

Assisted hatching: To increase the chance that an IVF-created embryo will implant in a woman’s uterus, some medical professionals use the “hatching” technique. This method makes it easier for an embryo to “hatch” out of certain layers of protein and then implant.

Gamete intrafallopian transfer (GIFT): Like IVF, the GIFT process harvests egg and sperm from intended parents. Instead of fertilizing the egg in a laboratory dish, however, this method mixes sperm and egg and then implants them into the fallopian tube for fertilization.

Zygote intrafallopian transfer (ZIFT): The ZIFT process is similar to the GIFT process, although the egg is fertilized before transfer to the fallopian tube.

SPERM, EGG OR EMBRYO DONATION
If the egg or sperm of an intended parent is not viable for a healthy embryo-creation process, gamete donation may be the next path to take. This way, intended parents can preserve at least one parental genetic connection to their child even if both parents cannot be genetically related to the child.

In addition to cases where parents’ sperm or eggs are not healthy enough for IVF, gamete donation is used in cases of same-sex family-building — lesbian couples will need a sperm donation and male couples will need an egg donation (as well as a gestational carrier, which you can read more about below). Gamete donations may also be used to avoid passing along a genetic disease for which one or both intended parents are a carrier. For people in these situations, an egg, sperm or embryo donation is the best of the infertility options available to them.

Like with other options for infertile couples, a reproductive endocrinologist will be able to tell you whether a sperm, egg or embryo donation is necessary or could be useful for your situation. Fortunately, there are many sperm, egg or embryo banks from which to find a donation, and intended parents can have the choice of an anonymous or identified donor. They can also choose important characteristics, like IQ, eye color, hair color, medical history, etc.

Before you choose to use a gamete donation, it’s important to talk to your fertility counselor about the potential challenges of doing so, including your future child’s identity as a donor-conceived child. Only once you are comfortable with these should you move forward with this ART process.

SURROGACY
For those parents who cannot carry a child to term themselves (either due to medical reasons or because they are a single male or gay male couple), surrogacy may be the answer. In this family-building method, an embryo is created by the intended parents (from their own sperm and egg or with a donor gamete) and then transferred into the uterus of a surrogate, who will carry the child to term for them. For intended parents who believe that becoming parents is more important than actually being pregnant, surrogacy is the best way to preserve a genetic connection to their child.

There are technically two kinds of surrogacy — gestational and traditional — but most surrogacy professionals today will only complete gestational surrogacies, where the surrogate is not related to the child she carries. Even in gestational surrogacy, the process is an emotional one, and both intended parents and surrogates should be prepared for the physical and emotional challenges that will await them.

To learn more about the surrogacy process, contact a surrogacy agency today or take a look around our website. While surrogacy may not be one of the infertility options that’s best for everyone, it may be possible for you.

ADOPTION
One of the more popular options for infertile couples is adoption, through which parents bring a non-genetically related child into their family. Adoption has changed a lot over the last few decades, and many are surprised at how positive an experience it can be for all involved. There are a couple of different paths if you choose to pursue adoption:

Private domestic infant adoption: In this adoption process, a pregnant woman chooses to place her child for adoption. She chooses the adoptive family, creates a relationship with them and is able to be a part of her child’s life as they grow up through open adoption.
Foster care adoption: There are many children in the foster care system who are eligible for adoption after their parents’ reunification plans have failed. Many of these children are older and may have special needs, but the foster care adoption cost is generally the least expensive of all adoption processes.
International adoption: While the options for international adoption are dwindling, it is still possible to adopt from certain countries other than the U.S. Children adopted internationally are usually older or have special needs, and the wait time for international adoption can be long.
It’s important to remember that adoption is not a “cure” for infertility, as it does not bring a child into your family that shares a genetic relationship with you. However, for those intended parents who believe that raising a child is more important than having that genetic relationship, adoption is the right path to pursue.

LIVING CHILD-FREE
Finally, one of the last options for infertility is choosing to live child-free. This is a serious decision to make — and only one that should be made after serious consideration by both members of an infertile couple. While this is certain one of the least popular options for infertile couples, there are some who choose to go this path.

Many times, when people choose to live child-free, it’s because they have already spent many years and funds trying to have a child of their own with no success. Rather than go through that process again, they decide that they can be happy living without children. They may have the joy of children in their life through nieces, nephews and neighbors, and they decide that missing out on the joys and pitfalls of parenting is not a huge loss for them.

Before you and your partner make this decision, it’s important that you talk it over in detail. A fertility counselor can also help walk you through this discussion.

DECIDING WHICH INFERTILITY OPTIONS ARE RIGHT FOR YOU
Because there are so many options for infertile couples, how do you decide which one is right for you? One of the best resources in this decision is your fertility counselor, who can not only inform you of the medical options available in your situation but also the practical and emotional requirements of each infertility option, including the differences in cost for each one. Intended parents should also consider speaking with a financial advisor before selecting a family-building option.

With the proper preparation and research, you can have the child you’ve always dreamed about through the family-building method that’s best for you. Every couple’s situation is different. Even if you’re not sure if surrogacy is right for you, you can get in touch with a surrogacy professional today to get more information about your infertility options.

References

surrogate.com, “Intended Parents, What are your infertility options today?”;

Appendix B–Prenatal Care

1st Trimester
If you haven’t yet received a COVID-19 vaccine, get vaccinated. COVID-19 vaccines don’t cause infection with the COVID-19 virus. Studies have shown COVID-19 vaccines don’t pose any serious risks for pregnant women or their babies. Vaccination can help pregnant women build antibodies that protect their babies. If possible, people who live with you should also be vaccinated against COVID-19.

Whether you choose a family doctor, obstetrician, nurse-midwife or other pregnancy specialist, your health care provider will treat, educate and reassure you throughout your pregnancy.

Your first visit will focus on assessing your overall health, identifying any risk factors and determining your baby’s gestational age. Your health care provider will ask detailed questions about your health history. Be honest. If you’re uncomfortable discussing your health history in front of your partner, schedule a private consultation. Also expect to learn about first trimester screening for chromosomal abnormalities.

After the first visit, you’ll probably be asked to schedule checkups every four weeks for the first 32 weeks of pregnancy. However, you may require more or less frequent appointments, depending on your health and medical history. In some cases, virtual prenatal care may be an option if you don’t have certain high-risk conditions. If you and your health care provider opt for virtual prenatal visits, ask if there are any tools that might be helpful to have at home, such as a blood pressure monitor. To make the most of any virtual visits, prepare a list of questions ahead of time and take detailed notes.

During these appointments, discuss any concerns or fears you might have about pregnancy, childbirth or life with a newborn. Remember, no question is silly or unimportant — and the answers can help you take care of yourself and your baby.

2nd Trimester

If you haven’t yet received a COVID-19 vaccine, get vaccinated. COVID-19 vaccines don’t cause infection with the COVID-19 virus. Studies have shown COVID-19 vaccines don’t pose any serious risks for pregnant women or their babies. Vaccination can help pregnant women build antibodies that protect their babies. If possible, people who live with you should also be vaccinated against COVID-19.

Your prenatal appointments will focus on your baby’s growth and detecting any health problems during the second trimester of pregnancy. Your health care provider will begin by checking your weight and blood pressure. Your provider might measure the size of your uterus by checking your fundal height — the distance from your pubic bone to the top of your uterus (fundus).

At this stage, the highlight of your prenatal visits might be listening to your baby’s heartbeat. Your health care provider might suggest an ultrasound or other screening tests this trimester. You might also find out your baby’s sex — if you choose.

In some cases, virtual prenatal care may be an option if you don’t have certain high-risk conditions. If you and your health care provider opt for virtual prenatal visits, ask if there are any tools that might be helpful to have at home, such as a blood pressure monitor. To make the most of any virtual visits, prepare a list of questions ahead of time and take detailed notes.

Be sure to mention any signs or symptoms that concern you. Talking to your health care provider is likely to put your mind at ease.

3rd Trimester

During the third trimester, your health care provider might ask you to come in for more frequent checkups — perhaps every two weeks beginning at week 32 and every week beginning at week 36.

Like previous visits, your health care provider will check your weight and blood pressure and ask about any signs or symptoms you’re experiencing. In some cases, virtual prenatal care may be an option if you don’t have certain high-risk conditions. If you and your health care provider opt for virtual prenatal visits, ask if there are any tools that might be helpful to have at home, such as a blood pressure monitor. To make the most of any virtual visits, prepare a list of questions ahead of time and take detailed notes.

Also, one dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine is recommended during each pregnancy — ideally during the third trimester, between weeks 27 and 36 of pregnancy. This can help protect your baby from whooping cough before he or she can be vaccinated.

You will also need screening tests for various conditions, including:

Gestational diabetes. This is a type of diabetes that sometimes develops during pregnancy. Prompt treatment and healthy lifestyle choices can help you manage your blood sugar level and deliver a healthy baby.
Iron deficiency anemia. Iron deficiency anemia occurs when you don’t have enough healthy red blood cells to carry adequate oxygen to your body’s tissues. Anemia might cause you to feel very tired. To treat anemia, you might need to take iron supplements.
Group B strep. Group B strep is a type of bacteria that can live in your vagina or rectum. It can cause a serious infection for your baby if there is exposure during birth. If you test positive for group B strep, your health care provider will recommend antibiotics while you’re in labor.
Your health care provider will also check your baby’s size and heart rate. Near the end of your pregnancy, your health care provider will also check your baby’s position and ask about your baby’s movements. He or she might also ask about your preferences regarding labor and pain management as you get ready for delivery. If you have specific preferences for labor and birth — such as laboring in water or avoiding medication — define your wishes in a birth plan. Review the plan with your health care provider but keep in mind that pregnancy problems might cause plans to change.

As your due date approaches, keep asking questions. Knowing what to expect can help you have the most positive birth experience

References
mayoclinic.org, “pregnancy week by week.”;

Appendix C–Can Diet Prolong Life?

Earth’s longest-lived people follow what author Dan Buettner calls blue-zone diets.

What’s the secret to living an extra 10 years? It’s never one thing. Rather, it’s a set of environmental factors that reinforce each other and that keep people reflexively doing the right things and avoiding the wrong things for long enough not to develop chronic diseases. For the past 20 years writing for National Geographic, I’ve identified and studied the world’s longest-lived areas, which I call blue zones. These places—Okinawa, Japan; Sardinia, Italy; Ikaría, Greece; Nicoya, Costa Rica; and the Seventh-day Adventist communities in Loma Linda, California—have the most centenarians and the highest middle-age life expectancy. Why? Residents live purposeful lives in walkable settings that keep people naturally active and socially connected. And they eat a diet that’s largely plant-based whole foods.

In 2019, as the COVID pandemic set in, photographer David McLain and I hatched the idea of searching for an American blue-zones diet. Thinking that our great-grandparents may have eaten similarly to people in the original blue zones, we searched for dietary surveys conducted in the early 1900s. To our dismay, we found that our own ancestors (who immigrated from northern and central Europe) brought their cows, pigs, and pickles with them.

Determined to find what food traditions other cultures, Indigenous and immigrant, had brought to the American table, we crisscrossed the country to find people who could tell us about these foods.

Here’s what we discovered: There is another American diet, one that could actually increase your life expectancy by up to 10 years and, in some cases, reverse disease. It’s not a fad diet invented by a South Beach doctor, a paleo diet marketer, or a social media influencer. This diet was developed by ordinary Americans, is widely affordable, is sustainable, and has a lower carbon footprint than a meat-heavy diet. Most important, it is hearty and delicious, developed over centuries by fusing flavors from the Old and New Worlds in ingenious and uniquely American ways.

We start in New England, looking at the traditional foods of the Wampanoag Native Americans. Their ancestors played a role in history in 1621 when they encountered recently arrived colonists. One man, Tisquantum, taught colonists how to plant corn, a local food. Carolyn Wynne, a Mashpee Wampanoag elder and Otter Clan mother, and her friend, food anthropologist Paula Marcoux, re-create an early 17th-century meal for us using typical Wampanoag foods.

As Wynne cooks over an open fire, she seems to be impervious to the heat. In the coals, she roasts squash stuffed with hazelnuts, dried blueberries, and maple syrup. In a pot off to the side, she boils nasaump, a cornmeal soup. In a third pot, she poaches pumpkin slices in sassafras tea. Though the Wampanoag hunted game and collected mussels and oysters, 70 percent of their diet came from plant sources.

Marcoux tends cast-iron pots hanging over another fire. In one, there is bubbling msíckquatash, a Wampanoag staple stew of hominy, beans, and squash, which Marcoux gussies up with green beans, onions, and herbs. The Wampanoag might also add Jerusalem artichokes, acorns, chestnuts, and walnuts (the nuts sometimes powdered to serve as thickeners). “My particular obsession with history affords me the fun of networking with long-dead cooks in their long-gone kitchens through archival and archaeological sources,” Marcoux says. “It’s a thrilling privilege to conjure their wisdom through fire.”

On the other side of the United States, at the northern tip of Hawaii’s Big Island, we see another version of Native ingenuity on the farm where Scott Harrison’s family has been cultivating native plants for three generations. It abounds with produce eaten here for hundreds of years: sweet potatoes, bananas, pineapples, papayas, mangoes, and breadfruits. In a neatly tended patch, Harrison reaches into the shallow water and extracts a taro plant, holding it up like a trophy: “You can eat the leaves like spinach and boil the stalks like asparagus,” he says. “Mostly we survived off of the root, which we mash into a paste that we eat every day.”

To the west, on the island of Oahu, in suburban Honolulu, 95-year-old Ruth Chang is preparing lunch. “I cook every day,” she tells me as she minces root vegetables. “Once you stop, you lose it.”

Chang’s demographic may be the longest-lived on Earth. Chinese American women living in Hawaii enjoy about 90 years of life expectancy, and the diet of Chinese Americans living there supports such longevity.

Since Southeast Asians began arriving in Hawaii over 170 years ago as agricultural workers, each ethnic group has introduced its own flavors and ingredients. The Chinese brought leafy cabbage, soybean products, and teas. The Japanese, miso and their own version of tofu. The Filipinos, tender tips of many plants such as squash and pumpkin. This melding of foods and cooking techniques has made Hawaii the place to experience Asian fusion cuisine that’s primarily plant based.

African Americans living in the Deep South have a long tradition of eating blue-zones-type foods. What began as a largely plant-based West African diet morphed with local Native American and European influences to produce a unique and vividly delicious cuisine. Dietary surveys going back to the 1890s indicate that most foods eaten by southern African Americans were vegetables and grains. Aside from salt pork added for flavor, animal products played a minor role.

On a steamy morning in Charleston, South Carolina, we’re in chef-historian BJ Dennis’s home, huddled around a pot of okra soup. Okra, garlic, onion, butter beans, tomato, thyme, searingly hot Scotch bonnet peppers, and the splendid funk of fermented benne (sesame) seeds fuse New and Old World flavors. My first bite delivers a tsunami of umami followed by eye-watering heat and a blush of pure happiness. (These are the world’s happiest places.)

Dennis is on a mission to bring back the cuisine of his rice-growing ancestors. Captured from places such as Senegal and Liberia, his forebears were brought to the Low Country of South Carolina and Georgia to cultivate Carolina Gold rice. Because of their expertise, some of the enslaved Africans were allowed gardens where they grew African staples and local ingredients. “We took the rustic soul of the Africans and the Native American techniques and made this special mash-up,” says Dennis.

The traditional West African diet consisted mostly of greens, root vegetables, black-eyed peas, okra, benne seeds, herbs and spices, and cereals like millet; meat was eaten only occasionally. When captured Africans were shipped to America, the plants and seeds of their homeland foods came with them. They entered into cultural exchanges with Native Americans, who shared some similar farming practices and food staples; both cooked with corn, sweet potatoes, and local bean varieties. The result was a blended, innovative cuisine.

On another day, in Texas, we’re with chef-historian Adán Medrano as he destroys the myth of Tex-Mex cooking. In his Houston kitchen he stirs a savory posole in one pot and in another a tomato-stewed rice, both dishes flavored with the Texas Mexican trio of garlic, cumin, and black pepper.

“Greasy, cheesy Tex-Mex food was largely an Anglo invention,” Medrano tells me. “Our traditional enchiladas were not slathered with cheese. We fill ours with carrots and potatoes.”

Born in San Antonio, in south-central Texas, Medrano, 74, grew up eating cactus, beans, corn, chilies, potatoes, onions, mushrooms, portulaca, amaranth, various berries, and occasionally game. These were the authentic foods of Texas Mexican cuisine, a far cry from Tex-Mex culinary corruptions like chicken fajitas or extra cheesy quesadillas. These types of whole, plant-based foods are also typical of other Latin American cuisines.

~ ~ ~

As we traveled the United States, we found the historical diets of these Indigenous and immigrant cultures being interpreted by a new guard of chefs and food pioneers. As they re-create traditional dishes, they are not only opening a treasure trove of largely overlooked culinary genius but also offering new expressions of the standard American diets—which may actually help us get that extra 10 years.

Conversely diet can also shorten your life expectancy. If you’re eating like a typical American, you’re probably going to die prematurely. This year more than 678,000 Americans will die from diseases or conditions associated with what they eat. These include common conditions such as high blood pressure, high blood sugar (type 2 diabetes), and high cholesterol. Collectively, we’ll spend more than four trillion dollars on health care, 20 percent on diseases linked to unhealthy diet choices, according to one study. It’s been estimated that we lose at least 13 years by eating a typical U.S. diet.

This may not come as a shock when you consider that each year the average American consumes a total 264 pounds of beef, veal, pork, and chicken; 123 pounds of sugar and caloric sweeteners, including some 39 gallons of soda pop; 16 gallons of milk; and more than 40 pounds of cheese, some of which tops our annual 46 slices of pizza. Seventy percent of our calories come from processed foods, containing thousands of artificial food additives, many of them known to cause cancer.

References

nationalgeographic.com, “This American diet could add 10 years to your life.” By Dan Butler;

Appenix D–Young Adulthood Is No Longer of Life’s Happiest Times

Is the midlife crisis a common rite of passage—or just a mythical concept that makes for grabby headlines? Research measuring well-being has typically provided solid evidence for such a period of soul searching. Over the course of a lifetime, happiness tends to start out high early in adulthood and decline in middle age, only to rise later in life. Unhappiness follows a mirror pattern—with the youngest and oldest tending to be the least unhappy and those in middle age being the most unhappy.

Plotting both qualities against age, the happiness curve is U-shaped (with the left and right peaks of the “U” corresponding to youth and old age), and the graph for unhappiness is depicted as a hump shape. Reduced to simpler terms, the midlife crisis seems to be real: happiness reaches its low point at around age 50,with peaks at age 30 and after age 70. This finding has been replicated in 146 countries and has held true for data reaching as far back as 1973—and does not just apply to Homo sapiens. Researchers have even identified similar patterns in nonhuman apes.

“It’s an established fact. We called it one of the most striking, persistent patterns in social science,” says David Blanchflower, a professor of economics at Dartmouth College, who co-authored one of the first papers on the U-shaped curve of happiness in 2008.

The curve was persistent for decades, he says, “until it wasn’t.” Blanchflower and his colleagues have recently released a National Bureau of Economic Research (NBER) working paper suggesting that this hump-shaped pattern in unhappiness has been replaced with a graph line that reveals a consistent decrease in unhappiness with age. This pattern is driven by an increase in unhappiness among young people both in absolute terms and relative to older people. In a follow-on blog post, Blanchflower has shown there has been a corresponding decrease in happiness in this group, leading to a similar change in the U-shaped pattern in happiness by age: now the line on the graph shows a consistently increasing line.

The study on the longitudinal changes in unhappiness analyzes data from the Centers for Disease Control and Prevention–administered Behavioral Risk Factor Surveillance System from 2009 to 2022. In particular, the authors tracked those who answered “30” to the question: “Now thinking about your mental health, which includes stress, depression, and problems with emotions, for how many days during the past 30 days was your mental health not good?”

“We have to focus on the people at the extremes,” Blanchflower says. “Think about those who are most susceptible to commit suicide, to have deaths of despair. These are the people who say, ‘Every day of my life is a bad mental health day.’” Between 2020 and 2022, more than half of respondents reported no bad mental health days. But 7 percent acknowledged exactly 30. The proportion of those with this response nearly doubled from 1993 to 2023. That rate has grown most quickly among the young, especially women 18 to 25 years old. “This fact alone is the most striking and scary: my estimates are that 11 percent of … young women are in despair,” Blanchflower says.

Carol Graham, a senior fellow at the Brookings Institution whose work focuses on well-being, acknowledges the seriousness of this finding. “We never really thought about the lowest point being in youth,” she says. “That is when people are just starting their lives. It shouldn’t be when they are most anxious, are most depressed and have no hope for the future. There is something profoundly wrong there.”

These trends have resulted in an altered relationship between age and ill-being. Between 2009 and 2018, despair remained hump-shaped, jibing with the preexisting research. A rapid rise in despair before age 45, especially before age 25, however, means that in 2019 unhappiness showed up more frequently at younger ages. “Danny Blanchflower has been hell-bent on showing the U-curve in so many countries…, and all of a sudden he’s writing a paper that’s showing the opposite,” Graham says.

“The question is,” Blanchflower says, “why didn’t I see this?” At first, he focused on deaths of despair among a narrow population: middle-aged white individuals without a college degree. Later, as he put it, he “thought that everything was COVID.” Now, Blanchflower says, he sees that was an error. “COVID extended trends that had existed before,” he says.

In their NBER paper, he and his co-authors replicated these findings using data from the U.K. and found evidence suggesting similar patterns in Australia, Canada and New Zealand. Based on a dataset covering 34 countries from 2020 to 2023 from Sapien Labs’ Global Mind Project, the authors showed that ill-being is currently at higher levels at younger ages—and the trend is not a hump shape—across these countries. “We thought it was the U.S., but … we’re seeing it everywhere, and that’s why we’re panicking,” Blanchflower says.

In the follow-on blog post, he and one of his co-authors also investigated trends in happiness to test whether the U-shape curve in well-being has correspondingly shifted. Plotting data collected from 2005 to 2018 and in 2022, the researchers demonstrated that during the first years of the survey, the traditional U-shape persisted, while in 2022 the data showed a constantly rising curve, with young people at the lowest point at its left and the graph line steadily trending upward with age. “I think we should be pretty shocked,” Graham says about the results. “The U-curve is not only an intuitive finding, but it’s also been very consistent across most countries in the world.”

In their NBER working paper, he and his co-authors focused on unhappiness and excluded happiness data because they were investigating negative life outcomes. Poor mental health is correlated with school absenteeism, psychiatric hospital admissions and suicide rates. “Medically, unhappiness is simpler,” Blanchflower says. “If you go back to [previous research], people who [were] significantly unhappy were the people who committed to suicide, had drug overdose deaths or died from alcohol poisoning. We’re looking at things that give us indicators of bad stuff that might come.”

There is no definitive consensus on the driver of the decline in happiness and rise in unhappiness among young adults, though Blanchflower believes the trend is driven by cell phone and social media usage. “What you need here is something that starts around 2014 or so, is global and disproportionately impacts the young—especially young women,” he says. “Anybody that comes up with an explanation has got to have something that fits that. Other than cell phones, I don’t have anything.”

Regardless of the cause, however, “this is a global problem,” Blanchflower says. “We’re past the point of measuring. We should be out doing pilots, trying to figure out what might work. We should be trying to come up with solutions…. Tell me what we can do to help these young people who are in trouble.”

Resources

scientificamerican.com, “Young Adulthood Is No Longer One of Life’s Happiest Times.” By Deena Mousa;

Appendix E–Girls are Going Through Puberty Much Earlier

These changes in the reproductive cycle could have serious ramifications for the physical and mental health of females worldwide.

ByStacey Colino

The average age of the onset of puberty has been dropping in the last century—with some girls starting to develop breasts as early as age six or seven. These shifts in the reproductive development timeline could have serious consequences for the physical and psychological health of the female population, experts say.

In a meta-analysis involving 30 studies, researchers found that the average age of the onset of puberty in girls throughout the world has dropped by three months per decade from 1977 to 2013—which adds up to more than a year earlier. The initial sign of puberty in girls is the development of breast tissue, with the onset of menstruation (a.k.a., menarche) coming later.

Now a new study in the May 2024 issue of JAMA Network Open suggests the timeline for both physiological markers seems to be getting younger. This study found that among 71,341 females born in the U.S. between 1950 and 2005, girls have been getting their first periods at a younger age and it’s taking longer for them to become regular. During the 55-year span covered in the study, the number of people experiencing early menarche (defined as younger than age 11) nearly doubled to 16 percent.

“It’s well documented, and it’s a worldwide phenomenon,” says Lisa Swartz Topor, an associate professor of pediatrics at The Warren Alpert Medical School of Brown University and Hasbro Children’s Hospital in Providence, Rhode Island. As for why it’s happening, at this point, “there are more questions than there are answers,” Topor says. “This is a confluence of a lot of different things—the overarching theme is changes to our world in the last two centuries.”

At any age, the onset of puberty is triggered by the hypothalamus in the brain, which secretes gonadotropin-releasing hormone (GnRH). GnRH—which has been called “the key regulator of the reproductive axis”—in turn stimulates the pituitary gland to secrete luteinizing hormone and follicle-stimulating hormone, which get puberty started. In girls, these two hormones signal the ovaries to start releasing estrogen and progesterone, which leads to breast development, the development of pubic hair, the onset of menstruation, and body shape changes.

Besides the potential long-term health repercussions, with early puberty, “your child might start to look or act like a teenager before you expected,” says Natasha Chaku, a psychologist and an assistant professor in the department of psychological and brain sciences at Indiana University in Bloomington. As a result, “parents may need to have conversations about how their bodies are going to change earlier than they expect.”

What’s responsible for the early timetable

It’s a multifactorial issue, according to experts. For one thing, childhood obesity rates have been rising since the 1970s and some studies have linked obesity to early puberty (a.k.a., precocious puberty) in girls.

This is partly because body fat is no longer viewed as an inert tissue; rather, it’s now known to act as an endocrine organ, secreting various hormones that can have head-to-toe effects throughout the body.

In particular, “obesity can be associated with the release of different hormones—including insulin, insulin-like growth factor 1, and leptin—into the bloodstream,” says Aviva Sopher, an associate professor of pediatrics at the Columbia University Irving Medical Center in New York. These hormones can affect appetite and satiety and the accumulation of body fat, among other bodily functions, and they can impact the hypothalamic-pituitary-gonadal axis and thus the timing of puberty.

In addition, girls with obesity have been found to have higher concentrations of estradiol (a form of estrogen)—which may contribute to early breast development and early puberty—than girls with a normal weight.

The quality of kids’ diets also may play a role, especially if they’re low in fruits and vegetables, high in animal protein and highly processed foods, “which are associated with higher levels of sex steroids like estrogen,” notes Frank Biro, a professor of pediatrics at Cincinnati Children’s Hospital Medical Center. In fact, when researchers in China compared three different diets—a traditional, an unhealthy, and a high protein one—they found that consuming a diet heavy in snacks, desserts, fried foods, and soft drinks (the “unhealthy diet”) was associated with precocious puberty in girls.

In addition, stress, including early life adversity tied to socioeconomic hardship or some form of abuse, may be a contributing factor. A study in a 2023 issue of the journal Psychoneuroendocrinologylinked high stress levels in early childhood with a higher risk of precocious puberty in girls.

“The timing of puberty is stress-sensitive,” says Jane Mendle, a clinical psychologist specializing in mental health during the transition from childhood to adolescence and an associate professor of psychology at Cornell University. “Kids with prepubertal histories of stress and adversity are more likely to go through puberty early.” One hypothesis is that this is because the stress response is also governed by the hypothalamic-pituitary-adrenal (HPA) axis, which influences the onset of puberty.

Some research has even suggested that stressors during the COVID-19 pandemic—including increased screen time, social isolation, physical inactivity, less access to healthy food, and other factors—may be associated with a recent increase in precocious puberty in girls in New York City.

These factors are associated with overproduction of sex hormones such as estrogens and testosterone, rather than direct effects on the brain.

Endocrine disrupting chemicals

Meanwhile, a growing body of research suggests that endocrine disrupting chemicals, such as phthalates, bisphenols, and others, that are found in everyday items may be contributing to these changes.

“A lot of endocrine disrupting chemicals that are ubiquitous in our environment have similar actions to estrogens,” Sopher says. As a result, high exposure to these chemicals can essentially hijack the body’s hormonal environment in ways that alter reproductive development.

For example, a study in a 2023 issue of BMC Medicinefound that precocious puberty in girls may be driven partly by exposure to perfluorinated compounds, which are present in numerous everyday products, including stain repellents, paints, waxes, polishes, electronics, food packaging, and more.

A study in a 2023 issue of Environmental Health Perspectivesconcluded that girls with higher residential exposure to particulate matter in air pollution—while they’re in the womb and throughout childhood—tend to get their periods earlier than those with low exposure.

Resources

nationalgeographic.com, “Girls are going through puberty much earlier. There may be several reasons why.” By Stacey Colino;

Appendix F–Here’s how your Voice Changes as you Age

Do you sound…old? If you’ve noticed your voice changing as you age, you’re not alone. Vocal changes are common in aging adults—but while some voices ripen and mellow with age, others are dismayed to find themselves warbling, whispering, or struggling to speak. Here’s why our voices change as we get older, and when it may be time to check with your doctor.

Physical changes

As we age, reductions in muscle mass and changes in posture can make it harder to produce the same sounds that came easily in the past. Singers report deepening or tremulous voices; speaking volume can also decline, especially in people suffering from swallowing disorders or neurological issues like Parkinson’s disease. The vocal folds or cords, the complex structure that vibrates to produce the voice, can lose tone and elasticity—bowing, shrinking, or forming gaps that will change your speaking tone.

“The cellular makeup on the vocal folds actually also changes,” says James Curtis, a speech-language pathologist at Weill Cornell Medicine. Combined with the weakening of breath capacity, along with changes in muscle tone and posture, this “is a recipe for disaster in terms of a smooth voice quality and a voice that isn’t breathy, rough, strained, or gravelly.”

Though the vocal folds are essential in voice production, however, they’re not always the main culprit in an “old” voice. In fact, many of the inconveniences that accompany aging can damage the voice, too. So it’s no wonder that up to one in three older adults reportedly experiences dysphonia, or an alteration in “normal voice quality.” Though symptoms vary widely, the most common voice issues in older adults are a decrease in loudness; a hoarse, raspy, or gravelly vocal quality; and vocal fatigue.

A matter of perception

These changes usually come on slowly, with presbyphonia, or “aging voice,” striking some as early as their fifties. Not everyone experiences voice changes with age, but those that do notice. So do their friends, children, and acquaintances.

While recent research suggests that people identify older voices with wisdom and good storytelling skills, study participants consistently assign negative connotations to older voices. Some view older voices as proof an individual is less flexible or cogent, playing into worn stereotypes about the abilities and worth of elderly people.

Sex and the aging voice

Women are especially prone to such stereotyping, and the vagaries of biological sex don’t help. Voice experts have long attributed vocal changes in women to the hormonal fluctuations of the female reproductive cycle. In the 19th century, female opera stars were regularly put on vocal rest during their periods, and opera singers still complain of premenstrual vocal changes; in Ukraine, some opera companies even offer their female singers paid leave during menses.

So it might not come as a surprise that menopause is also blamed for some vocal changes— particularly differences in pitch and vocal power. Dryer mucous membranes due to falling estrogen could be to blame, as could increased androgens, the same hormones that deepen the male voice. As a result, some patients use hormone replacement therapy to delay or prevent voice changes in menopause.

But research on sex differences in the aging voice is still in its infancy, and researchers lament the dearth of studies devoted to maintaining the voice in menopausal women. “There’s a growing interest in this area,” says Curtis. “But it shouldn’t be a growing interest. It should be well established.”

Treating voice disorders in aging adults

Nonetheless, the vast spectrum of factors that contribute to age-related voice changes is still being plumbed by researchers eager to understand the effects of everything from genetics to career on the aging voice. And because of the sheer number of factors that go into producing words, says Curtis, that research can be slow going. “These changes are multifactorial,” he explains. “Our voice is a whole-body behavior.”

As a result, treatments that preserve or improve vocal function for aging adults vary widely. There’s medication like hormone replacement therapy or thyroid medication targeted at reducing an enlarged thyroid, which can cause vocal changes. But the front-line treatment is usually non-invasive voice therapy, a personalized physical therapy prescribed and facilitated by speech-language pathologists. Usually, such training includes a regimen of vocal, breathing, and even postural exercises designed to maintain vocal range, preserve volume, and tackle individual issues.

Overall, write geriatric voice specialists Robert T. Sataloff and Karen M. Kost, “Surgery is unnecessary for the vast majority of patients with age-induced dysphonia.” But there are a variety of procedures designed to pinpoint more severe vocal problems. Vocal fold injections, an outpatient procedure in which a filler is injected into one or both vocal folds, can shore up deteriorating or paralyzed vocal cords, strengthening the voice and helping them function better. In thyroplasty, the vocal cords are repositioned with the help of a mesh implant that’s inserted via a small hole in the neck, improving the voice and restoring function to weak or paralyzed vocal folds. Chronic hoarseness can sometimes be treated with surgeries that pinpoint the laryngeal nerves. And the list goes on.

That said, many voice problems can be avoided. “We need to be thinking about our voice just like any other part of our body and trying to take care of it,” says Curtis. And surprisingly, some of the most effective voice preservers have little to do with the mouth or throat.

Keeping active and fit as you age can help preserve muscle mass, strength, and stamina and benefit the respiratory system, while good oral health can forestall issues with saliva and mucous membranes. Voice experts also stress the importance of nutrition and hydration, suggesting older adults drink plenty of water, eat healthy foods that can help maintain cellular function, and consider using a humidifier at home. And while researchers may disagree on the role various factors play in voice preservation, they’re unanimous on one point: Smoking not only irritates the voice, but can cause sometimes-fatal cancer in the very organs that produce your speech.

The psychological ramifications of unwelcome voice changes can also lead to other health problems, says Curtis, who says some older adults fall into a “vicious cycle” after losing confidence in their voice. “If an individual is feeling like their voice is changing, and it’s impacting their ability to participate in personal, professional, or social endeavors, [they] can start to withdraw socially and become depressed,” he says. That leads to reduced physical activity and increases isolation and frailty, reducing quality of life and even endangering the health of older adults.

Is self-acceptance part of the solution? Possibly. Older adults who fear stigma or who have trouble coming to terms with their age-related voice changes can miss out on effective interventions, recent research suggests. Add ageism to the mix—consider, for example, the plethora of demeaning “old lady voice” filters available to video producers—and the picture gets even more complicated.

But researchers are increasingly trying to reframe many “disorders” of the aging voice as neutral realities that simply reflect the passage of time. And, it turns out, older adults may be following suit: Up to 80 percent of older adults with dysphonia actually decide to skip treatment, studies have found.

Nonetheless, says Curtis, there’s no shame in seeking out help. He advises that individuals who have experienced drastic or sudden changes and those who notice impacts to their ability to participate in their personal, social, or professional endeavors to talk to a doctor. “Our voice is very personal,” he says. At any age, he emphasizes, “It’s really about the patient.”

Resources

nationalgeographic.com, “Here’s how your voice changes as you age.Some voices mellow with age, while others may struggle to speak. As our physical bodies change, our vocal cords are impacted, too.” By Erin Blakemore;

Appendix G–Why Outdoor Adventure is Important for Women as they Age

“Where are all the other older women?” I was 55 years old, and this question popped into my head every time I went out surfing. I would see a lot of men my age—and older—on the waves, but very few women.

I sought out those elusive, adventurous older women for my latest book Tough Broad, From Boogie Boarding to Wing Walking, How Outdoor Adventure Improves Our Lives as We Age. I accompanied an 80-year-old scuba diver into the Pacific. I walked a suburban park with a 93-year-old backpacker. I birdwatched and I sea kayaked.

I also did a deep dive into the current research on aging. What I found after all this was a compelling argument that having adventures outside is the best thing that we women can do to ensure that we will live happier, healthier, and more fulfilling lives as we get older.

Here are five important things I learned during the writing of this book.

1. Mindset matters for aging well.

The messaging around aging for women is sadly very toxic. We are told we are on a rapid decline, and many women feel invisible. Yet research shows that the way we look at our own aging predicts how well we age. So if you have a negative view of aging, you have a statistically higher chance of a cardiac event or cognitive decline, and earlier in life too.

The exciting part is that the opposite is also true: If you think of aging as a time of exploration and exhilaration, you will be happier, healthier, and live seven years longer. There’s a lot of science behind that. For example, a 2022 study of 14,000 adults over 50 found that those who were the most positive about aging had a 43 percent lower risk of dying from any cause over the next four years than those who were the least positive about aging.

But these studies don’t tell us how to get that positive mindset, especially in the face of such negative messaging about our aging journey. However, I had a sense that I had the answer: outdoor adventure.

2. Outdoor adventure can change our mindset on aging.

I jumped in the ocean with the Wave Chasers, a group of women in their sixties, seventies, eighties, and beyond (one member is 99 years old!) who boogie board together in San Diego. I wanted to understand why they chose to take up this sport—and what they get out of it.

Loraine Vaught told me that boogie boarding had changed her life. When I asked how, she pointed out to the big, cold Pacific Ocean; look at the nerve it took to step in, look at the bravery one needed to be tumbled by waves, look at the way each Wave Chaser helped one another, look at the fun they were having. What she was saying was that none of the Wave Chasers were doing what was expected of them at their age. They certainly did not see themselves as frail or cognitively impaired—or boring!

This made me realize that if you go outside and pick an activity that makes you feel exhilaration, exploration, and physical vitality—even something as simple as boogie boarding—this is a direct rebuke to everything you’ve been told about your aging journey. Now you’ve upended your own beliefs and expectations—and others’—of what you can and cannot do. Now you feel empowered about your future, not disheartened! I saw this over and over while reporting this book.

Also, I can’t stress this enough: Adventure is in the eye of the beholder. I went birdwatching with Virginia Rose, the founder of the nonprofit called Birdability that brings people with disabilities outside to birdwatch. To my surprise, birding had all the hallmarks of an adventure. We were on a quest. There was the anticipation of hearing a bird before you could see it. There was the adrenaline rush of then seeing it! There was the physical vitality of being in the elements; Virginia wheeled and I walked six miles that day, logging 52 species for citizen science. Also, I was pushing on my comfort zone by learning new things. Adventure, it turns out, is not defined by the activity per se, but how you feel doing it.

3. Nature is medicinal.

Getting outside is critical for you biologically—and there is so much science to prove it. Studies have shown that trees release chemicals called phytoncides that are really good for our immune system, while birdsong has been shown to calm our brainwaves. There’s also evidence that fractals—complex patterns found in coastlines, clouds, and ocean waves—can relax our brains.

Scientists have also shown that you perform significantly better on cognitive and memory tests after taking a walk outside. Your brain has been processing information outside in a way that isn’t highly taxing, as it can be when you’re in a place filled with harsh noises and angular patterns.

The general prognosis from all these studies is that 15 to 45 minutes in a natural setting of any sort will make a difference. Five hours a month can also help you maintain that emotional and physical restoration. But ultimately more is better—and the more remote and wild are the green space, the better it is for you too.

4. Awe is critical for us on a biological level.

I’m a pilot so I’m used to adrenaline. But I wasn’t ready for the feeling I had when I went wing walking—standing on the wing of an airplane as it soars 3,000 feet in the air. “Why would I get out of a perfectly good cockpit?” I thought. But I tried it anyway. And as the pilot started doing loops, barrel rolls, and hammerheads while I stood there attached to the kingpost, I became ecstatic. It was adrenaline, of course. But there was something else. That’s how I came upon this concept of awe.

Awe is the feeling you get in the presence of something bigger than you, something mysterious. It’s this feeling of wonder, fear, and dread. And it’s more important for a healthy life than you might think. Scientists call awe a “reset button” for the brain because it shakes up your neural patterns in a way that makes you more open to new ideas. It also makes you think more creatively.

You don’t have to walk on a wing to feel awe either. You can just walk. One team of researchers asked a group of older adults to go on what they called an “awe walk,” during which they were to look at everything with childlike wonder. At the end of eight weeks, inflammatory markers for the awe walkers was significantly lower than the control group—a sign of better health—while they also reported feeling way less anxious and depressed.

Turns out things like the night sky, an eclipse, the Grand Canyon, even a tiny flower are all surefire triggers for awe. Going outside, in other words, makes it easy to cultivate wonder and therefore improve our well-being.

5. We actually can learn new things as we age—and learn better.

The culture insists that we are unable to learn as we age. You can hear it when people talk about confronting new things. They say, “I’m too old to do that.” But the brain has what scientists call “plasticity” even as we get older. We build new brain cells all the time. If our cognition begins to falter, we’ll lay down different neural pathways to figure out whatever problem is at hand. This is what often makes an older brain more innovative than its younger self—it’s finding more creative ways to circumvent its own problem areas. Learning something new is not only possible, it’s vital to keep a brain healthy and active.

That said I still believed it would be difficult to learn something new when I decided to take gyrocopter flying lessons as part of my research for Tough Broad. Turns out, I was a much better student than ever before! It wasn’t that I learned faster, but I learned better because I didn’t have a lot of the youthful angst and the need to prove myself. I was more focused, and I would ask questions without worrying about looking dumb.

I also interviewed Vijaya Srivastava, who learned to swim at 68. I asked if her age was a hindrance to her swim journey. On the contrary, she told me, it helped. For one, she loved that she no longer cared what she looked like in her bathing suit. Also there was urgency to learning this late in life. She knew she wasn’t going to get another chance. But most strikingly she said, “If I could learn to swim at 68, what else could I do?” Just that one thing opened up the world to her. And it could do the same for you.

Resources

nationalgeographic.com, “Why outdoor adventure is important for women as they age.” By Carolne Paul;

Appendix H–12 Ways to Feel and Look Younger

Phase Out Destructive Habits

The single best thing you can do for your health and longevity is quit smoking. Smoking has been indicted for a laundry list of ills from heart disease to lung disorders, all of which can foil your longevity plans.
Drink only in moderation. Alcohol infuses every cell, damaging genes and inflaming your liver. A glass of wine a day for women and maybe two for men, but no more, may be mildly beneficial.
Get your Zzzz’s. Your body needs down time to repair cells and rest your heart. And your mind needs dreaming to stay sane.
Find a doctor who specializes in geriatrics or anti-aging. Barbara M. Morris, RPh, author of Boomers Can Really Put Old on Hold, recommends an anti-aging doctor. But according to Marc R. Blackman, MD, chief of the laboratory of clinical investigation of the National Center for Complementary and Alternative Medicine (part of the National Institutes of Health), a geriatrician would be more mainstream and recommend fewer unproven treatments. “Anti-aging is like saying anti-puberty or anti-pregnancy. This is a natural process,” he says. Whatever their style, your new doctor may recommend yearly assessment of various biomarkers, including lipids, DHEA, estrogen, cortisol, thyroid, lung function, and micronutrient assays.
Cut saturated fat, up omega-3 fats. It’s gospel by now: eat less or no red meat; lose the cake and ice cream; consume more complex carbs, such as whole grains, fruits, and vegetables; and get plenty of fatty fish. The healthy fats in salmon, mackerel, and sardines help keep oxygen free-radical molecules from damaging your cells.
Consider moderating your total food intake. Studies in rats show that a 30% calorie restriction means longer life (no, it doesn’t just seem longer!). Blackman also cites studies in rhesus monkeys showing a gain in years from a reduction in food. Obviously, losing excess pounds means less strain on your system.
Be careful when tweaking your hormones. Morris swears by controversial human growth hormone — for her. Blackman is no fan. “There have been big studies to determine the relationship between decreases in human growth hormone and thinner bones, more body fat, and mood swings. Giving growth hormone can build muscle, but it has not been shown that the muscle is any stronger.” HGH has also been associated with water retention, carpal tunnel syndrome, high blood pressure, and blood-sugar fluctuations. “[HGH science] is not at a point where any responsible provider could recommend it,” Blackman says. And what about the other substance — a steroid called DHEA — often recommended for aging? “Dramatically less evidence than HGH!” exclaims Blackman. As for estrogen and progesterone replacement, it’s been in all the papers. The combo therapy may increase, rather than cut, the risk of cancer and heart disease. Many natural alternatives to these substances exist — your own situation should dictate your decision, but always consult your doctor.
Supplement, supplement, supplement. Most of us suffer from “overconsumption malnutrition” — too much of the wrong things, Morris says. She takes a fistful of vitamins and minerals each morning. Even the cautious American Medical Association recently endorsed taking a daily multivitamin. In addition to the effective antioxidant vitamin C, Morris says CoQ10, vitamin E, alpha lipoic acid (another antioxidant), and perhaps some of those “mental acuity” mixtures in the health-food store should be in your medicine cabinet. Again, your doctor can help you fashion routine.
Reprogram your vision of old age. A study at Yale recently showed that those with a positive view of growing older lived seven years longer than those who griped about it. Morris works with young people and “they forget things all the time and never refer to ‘having to a junior moment.’”
Kick guilt out of your life! Laura Berman Fortgang, author of Living Your Best Life, says: “Be future-minded. Guilt and regrets are part of the past. Evolving and changing is how we stay young.”
Don’t be afraid to make a big change. Fortgang says it’s never too late to move, join the Peace Corps, change careers, get married, or get a divorce. “Don’t say you’re too old,” she says. “Sometimes [earlier] decisions need to be changed.” She and Morris also say plastic surgery can be life-enhancing if you do it to look and feel better, not to change your life overnight.
Morris also half-jokingly advises that people never retire. “Retirement is a contagious, debilitating disease.” Take some time off for a vacation and smell the roses, she advises. But don’t get so intoxicated by the roses that you don’t come back and do something useful. “Those roses could turn into daisies,” she says, “as in pushing up daisies.”

Resources

webmd.com, “12 Ways to Feel and Look Younger.” By WBMD Editors;

Appendix I–Your Body Ages in two “bursts,” at 44 and 60

In a newly published study, Stanford scientists reveal we don’t age gradually, as has been traditionally believed. Instead, we age at two significant “bursts” across our post-puberty lifespan: one in our mid-40s, the other in our early 60s.

The molecular changes that occur during each period could explain seeming sudden signs of aging such as the appearance of wrinkles, sagging skin, graying hair, muscle and joint pain, and increased vulnerability to viral infections.

“This study reveals why many people start to ‘feel’ their age rather suddenly,” explains John Whyte, a family medicine physician and a former director for the U.S. Food and Drug Administration, who was not involved in the research. At the same time, he says, it “challenges the traditional view that aging is a slow, continuous process.”

David Sinclair, a molecular geneticist, longevity researcher, and professor at Harvard Medical School, who was also not involved in the research, puts it more pointedly: “The research seems to fly in the face of current models of aging, particularly the epigenetic clock and other gradual and linear changes such as steady increases in blood sugar levels.”

And while the study may not apply to everyone, Sinclair calls its findings “provocative” and says it indeed shows “large shifts in our biology in our 40s and 60s relative to other times of life post puberty.”

The study also follows an evolving scientific view about how we age as other studies have pointed to similar periods where sudden aging seems to occur. “Plenty of research has shown that changes related to aging may occur more suddenly during certain times in our lives,” explains Mitch McVey, a biologist at Tufts University who specializes in DNA repair and molecular mechanisms linked to aging, who wasn’t involved in the research.

One of the Stanford study’s authors, microbiome scientist Xiaotao Shen, says the team’s work also builds on previous findings, “collectively demonstrating that aging is nonlinear.”

But these findings don’t have to make you dread hitting your 40s and 60s. Understanding how and when we age can help individuals and healthcare professionals take specific steps to prevent—or at least prepare for—some of the most undesirable outcomes of aging.

How changes at the molecular level affect you

For nearly two years, the Stanford scientists behind the research measured molecular activity by analyzing the microorganisms contained in blood, skin, nose, mouth, and gut samples that were taken every three to six months from 108 study participants of various ethnic backgrounds, whose ages ranged from 25 to 75.

The scientists used the samples to examine more than 135,000 different molecules and microbes including metabolites, lipids, proteins, and precursors to proteins (RNA molecules) that are known to be associated with immune health, cardiovascular function, metabolism, kidney function, and muscle and skin structure.

Altogether, the samples formed some 246 billion data points (biomarkers) for the team to measure across the 50-year age span of the participants. “We were looking for when changes and disruptions most commonly occurred at a molecular and biochemical level,” explains Michael Snyder, a co-author of the study and the chair of the department of genetics at Stanford Medicine.

The results show that 81 percent of the molecules didn’t change continuously—as would be expected with linear aging—but instead transformed significantly around ages 44 and 60.

At age 44, some of the observed changes occurred in cells affecting metabolism—which could explain why we have a harder time absorbing and processing caffeine and alcohol as we get older; fatty tissue proteins—which could explain higher cholesterol levels and unexpected weight gain in middle age; and connective tissue proteins associated with skin and muscle structure—which could explain why skin starts to sag, wrinkles appear, and “why people have more issues related to muscle strain and injuries,” explains Snyder.

At age 60, the team observed more of those same molecular changes along with notable new fluctuations in molecules related to kidney function and immune health. This, Snyder says, could explain why older adults are more vulnerable to diseases like COVID-19 and why cancer rates, kidney issues, and cardiovascular disorders increase so dramatically in our 60s.

Samuel Lin, an associate professor of surgery at Harvard Medical School and a plastic surgeon at Beth Israel Deaconess Medical Center in Boston, who was not involved in the research, explains that the molecular changes that suddenly occur during the first aging burst may be further exacerbated when we hit our 60s—with each period resulting in visible outcomes such as declining collagen and elastin production, reduced melanin, and hormonal changes that contribute to diminished skin quality and the graying and thinning of hair.

“These visible signs of aging are direct results of the underlying molecular and microbial shifts occurring within our bodies,” he says.

Beyond the visible, Lin notes that shifts in microbial communities throughout the body can also promote inflammation—a key factor in many age-related disorders and chronic conditions.

Identifying such molecular changes occurring at these two distinct periods “is useful because it tells us what things are likely to go wrong at these stages of our lives,” says Venki Ramakrishnan, a Nobel prize-winning scientist and author of Why We Die: The New Science of Aging and the Quest for Immortality, who was not involved in the research.

Limitations and unanswered questions

Despite the benefits this knowledge could bring, the study has a number of limitations and leaves important questions unanswered.

For instance, one major caveat is that all the study participants live in California—increasing the likelihood of their having shared backgrounds, lifestyles, and similar environmental factors. “Because of this, our cohort may not fully represent the diversity of the broader population,” says Shen.

The molecular changes observed in the study were also only tracked across multiple individuals of varying ages rather than within the same individuals over time. This missing piece may be essential because previously published Stanford research shows that everyone ages differently, so the study’s results may be different in the same individual tracked for decades.

The study also did not include any participants over age 75, “which means it doesn’t account for aging patterns in the later stages of life,” adds Lin.

Of significant note, the research also doesn’t get to the root of what’s causing these changes and doesn’t account for variations in diet or behavioral shifts such as someone experiencing high amounts of stress or diminished sleep quality. It also doesn’t consider whether a person smokes, drinks, or takes prescription medications that might also explain some of these molecular alterations.

In fact, other research shows that some people experience a “midlife crisis” in their late 30s and early 40s or a “late-life crisis” in their late 50s and early 60s—two time periods that coincide with these aging “bursts.” In other words, “it’s possible that associated psychological and lifestyle changes may be responsible for these changes in aging and not due to our inherent biology,” explains Sinclair.

Can these bursts of aging be prevented?

Regardless of what’s behind these molecular changes, “the underlying causes of aging are very likely ones we have already identified,” says Ramakrishnan, so we have a good idea about what can be done to prevent some of its most undesirable outcomes.

For one, Shen advises reducing your alcohol and caffeine intake when nearing your 40s or 60s as it becomes harder for the body to metabolize both substances.

Snyder recommends keeping an especially close eye on cholesterol levels and speaking with your healthcare provider as you enter your 40s about medications that may be effective in managing it and reducing other fats in the blood.

He also stresses the importance of regular exercise, “especially lifting weights to keep muscle mass,” as well as drinking more water to counteract age-related kidney issues and consuming more antioxidant-rich foods to reduce adverse effects of oxidative stress.

Sinclair suggests limiting red meat and processed meat intake, eating more vegetables, prioritizing sleep, minimizing stress, keeping excess weight off, and staying active.

Also consider using skincare products that contain retinoids or antioxidants like vitamin C, “which can help maintain skin health by boosting collagen production and reducing free radical damage,” advises Lin.

“While we cannot stop the aging process,” he adds, “understanding the molecular changes highlighted in this research empowers us to take steps that can enhance our quality of life and help us age more gracefully.”

Resources

nationalgeographic.com, “Your body ages rapidly in two ‘bursts,’ at 44 and 60.” By Daryl Austin;

Appendix J–When does Old Age Begin?

Today’s 60 year olds don’t feel as old as a generation ago. New data suggests old age is more of a social construct than an objective biological reality.

Trying to stay forever young? It’s a popular goal: The anti-aging market, valued at $40 billion, is estimated to hit $60 billion by 2032. To stave off old age, people slather on wrinkle cream, pop supplements, and lift weights, among other interventions.

Though aging is often portrayed as a problem to fix, it’s more modifiable than you might think. According to the latest science, there’s no clear biological tipping point marking the transition from midlife to late life, says Eric Verdin, president and CEO of the Buck Institute for Research on Aging in California.

“There’s an incredible amount of variability between different people,” says Verdin, who favors using someone’s biological age—which is how old your cells and tissues are—rather than their chronological age, which is the number of years you’ve been alive. (Read how inflammation impacts aging.)

That belief has started to upend the status quo: A recent study published in the journal Psychology and Aging shows that the age at which someone is considered old is shifting up.

Middle-aged and older adults nowadays feel younger than similar aged people did 10 to 20 years ago, according to the study led by Markus Wettstein, a researcher at Humboldt University in Berlin, Germany.

People are living longer, which partially explains this trend. But the findings may also reflect bleak views toward aging, particularly in the Western Hemisphere.

“People postpone old age as they do not want to enter this rather undesirable life phase,” Wettstein and his colleagues said in an email to National Geographic.

The history of old age

For much of human history, a person’s ability to complete tasks or contribute to their family and community shaped the perception of old age.

Throughout the Western Hemisphere in the late 19th and early 20th centuries, retirement marked when the focus shifted to an individual’s chronological age, not their abilities.

The average American retires at 62, which is around the time most officials and governments consider a person old. The range of 60 to 65 has remained relatively consistent over time, even as lifespans extended and humans experienced major social and economic changes.

Across the board, aging is the strongest risk factor for most non-communicable diseases such as cancer, diabetes, and Alzheimer’s. Most people will spend a significant fraction of their lives affected by conditions like these. By some estimates, nearly 95 percent of U.S. adults over 60 have at least one chronic condition, while nearly 80 percent have two or more. (Read how to take care of your brain as you age.)

Yet chronological age may not be a good indicator for defining old age, the new study says. Rather, individuals might enter old age at different times, according to their own perceptions.

And it’s true that no one wants to be old, especially as aging stereotypes have become more negative over the last 200 years—fueling what some call a worldwide crisis of ageism. Ageism, which can be as subtle as hiring a more youthful candidate or as blatant as disrespect, leads to social isolation, poor health, and even earlier death, according to the World Health Organization.

Becca Levy, a professor of epidemiology and psychology at Yale who was not involved in the new study, has spent much of her career untangling the downstream effects of age beliefs, which she detailed in her book,Breaking the Age Code.

“More negative age beliefs can lead to worse physical, mental, and cognitive health,” Levy says, whereas positive ones precipitate better health. One of Levy’s analyses estimates that a one-year cost of ageism in the United States totals $63 billion.

“Aging is colored by culture,” Verdin says. “In the Western world, youth is valued, but in Eastern cultures such as China and Korea, aging is associated with wisdom and is considered a virtue.”

When does old age begin?

Over the last century, scientific interest in aging has surged. Investors and government funders have poured billions into longevity research, leading to new insights into the aging process.

Cells can now be reprogrammed to restore youthful function. New drugs can eliminate senescent cells that drive inflammation. Dietary interventions such as intermittent fasting and caloric restriction have shown potential to extend life.

Despite this progress, scientists still quibble over what aging is and when it starts.

For one, there’s not a definitive way to measure it. Our bodies may age faster or slower depending on what has happened during our lives. Some major events, such as stressors or chronic illnesses, can make us age “faster,” thereby accelerating our biological age.

While certain physiological phenomena, like puberty and menopause, mark milestones along life’s path, old age isn’t defined by universal markers. Aging is a multifactorial process characterized by the accumulation of damage and degeneration across physiological pathways. This cascading deterioration eventually disrupts normal cell and tissue function.

In the last 30 years, scientists have searched for distinct metrics that accurately represent a person’s biological age. Certain factors like physical capability, lipid profiles, and DNA damage have been flagged as potential biomarkers. But currently, there is still no gold standard tool to assess healthy aging. (Learn how one pregnancy can add to a person’s biological age.)

“Aging is not something that happens abruptly,” Verdin says. “It’s a continuum, which makes it difficult to define.”

Investigating superagers

Still, everyone ages differently, and some live long and thrive. These so-called “superagers,” who remain relatively youthful and healthy long after age 70, have fascinated scientists.

By studying them, Verdin and other aging researchers hope to increase non-superagers’ healthspan, or the amount of time they live without chronic disease.

By 2050, 1 in 3 people in the world will be 60 years or older, a demographic shift that makes this research more pressing than ever.

“I hope our work will allow us to give people extra years of healthy life,” Verdin says, “and therefore change public perceptions and make people feel less negative about their own aging.”

Resources

nationalgeographics.com, “When does old age begin? Science says later than you might think.” By Ali Patillo;

Appendix K–Want to Live Longer?

By making healthy lifestyle choices, you can self-engineer genetic alterations to prevent disease and boost longevity.

By Michael F. Roizen

Take a moment to visualize your favorite place in the world that requires you to walk up an incline. Maybe it’s the Spanish Steps in Rome or the Potala Palace in Tibet. Or maybe it’s a serene hill in your local park. Or the top row of your favorite team’s stadium.

Now imagine that you’ve reached the summit. Take a look down at the other folks trekking toward you. You will see two kinds of people.

First, there’s the spry set. These are the bouncy beings that kangaroo from the bottom to the top. They’re smiling, laughing, barely breaking a sweat, and fully enjoying the journey. They’re excited about reaching the destination and—despite the fact that it takes some effort—can’t wait to experience what awaits when they arrive.

Second, there’s the group that’s struggling. Those who have to stop and catch their breath 10 times on the way up. Every. Step. Takes. So. Much. Out. Of. Them. Huff. Puff. Are. We. There. Yet?

You’re probably more like one of these groups than the other. What’s the difference between them, besides their speed and the ease with which they travel? It might be their size or age, yes. It’s most certainly their overall health.

But you know what it’s less likely to be? Their genes endowed at birth. Instead, it’s their lifestyle choices.

The Great Age Reboot is the name my co-authors—Peter Linneman and Albert Ratner—and I gave our new book, published by National Geographic. The “great age reboot” is also our term for the transformation we see dawning: breakthroughs in health and medicine that will let us live longer and live younger; advances that will exponentially change our society, our economy, and our future.

To prepare for the great age reboot, you have to be willing to change—not only to get and stay healthy but also to have enough health to repair yourself when repairs are needed. There is certainly a fantastic future ahead. But to enjoy it and relish your longevity, you will need to be a genetic engineer now. The upside?

You will literally get to change your family medical destiny—if you want to.

In the United States about 40 percent of premature deaths—defined as occurring before age 75—are related to lifestyle choices, behaviors we can change. Lifestyle and genetics are intertwined, in that your lifestyle choices influence the ways that many of your genes function—and thus how your body functions.

Studies of human gene expression show that if you choose to make certain lifestyle changes, you can influence whether your genes are “on” or “off.” In fact, your choices can influence an estimated 1,200 of the 1,500 genes that are on and probably can influence the other estimated 21,000 that are off.

For example, after implementing changes to their physical activity, stress management, and diet regimens, men were able to turn off genes associated with prostate cancer growth and turn on a gene that produced a protein that causes cancer cells to self-destruct. The same principle applies for colon and breast cancer: Lifestyle changes switched on genes that fought cancer and turned off genes that promoted it.

You have the ability to change how your body works and reacts—and ultimately how healthy you are and how long you may live. You should build a strong foundation now.

Science tells us that by the time you are about 60 years old, 75 percent of your health outcomes are determined by your choices. That’s genetic self-engineering: Each healthy act switches on youth-promoting genes and switches off genes that cause you to age. This process is the result of millions of years of evolution. Good choices (and the proteins that are developed because of them) beget more good proteins, and the activation of bad genes begets more bad and destructive genes being turned on.

You have the ability to change how your body works and reacts—and ultimately how healthy you are and how long you may live. We’ll give you three main reasons your pursuit of optimum health and youth through lifestyle choices is an imperative.

You should build a strong foundation now. You probably know people who’ve survived a horrific disease, accident, or surgery—and it was said that their preexisting physical and mental strength fortified their bodies for battle and made them better equipped to endure stresses. That’s true with the recent COVID-19 pandemic: Over 80 percent of COVID-19 deaths were among people older than 65, and severe cases are more likely for those with preexisting conditions, such as obesity, diabetes, heart disease, chronic lung disease, and immune dysfunction.

The same thinking will apply when we’re talking about longevity—that is, healthy choices will help prevent chronic disease and set you up for a long life. The better your physical shape, the higher the chances that new antiaging procedures will “take” at a high level, with fewer complications. Stronger at the start means stronger throughout the entire race and all the way to the finish.

It’s unclear how many reboots you’ll get. Perhaps in a utopian 25th-century world, there will exist some dressing-room-like catacomb that allows you to walk into a booth, press a few buttons, and erase every cigarette you’ve smoked, every couch you’ve potatoed, every potato you’ve ever fried. But for the foreseeable future, it’s far more likely that your reboot chances will be limited. Your ability to maximize their effectiveness will depend on your commitment to improving your biology through proven means: nutrition, physical activity, sleep, not smoking, and stress management.

No matter what happens, your brain needs you. The human brain remains the final biological frontier. So even if science ultimately allows us to correct our cells, genes, and other mechanisms that make our bodies work, when your brain goes, you will too. To maximize the promise of a longer-lasting youth, it’s imperative that you self-engineer your DNA switches to protect your brain—and the steps are the same as those you can take to protect the rest of your body.

The actions outlined below have been shown to have the most influence over your biological function. You’re not going to behave perfectly all the time. Your longevity depends more on the aggregate of what you do most of the time. How can we collectively get to better decisions?

We are in a peak period for access to information and have the most medically advanced health industry of all time. Yet two-thirds of Americans are overweight or obese, and millions will die or become ill from choice-related health problems, including heart disease, lung cancer, stroke, diabetes, and dementia (yes, the data show that healthy lifestyles are associated with a 60 percent reduction in the risk of developing dementia).

Finding the right way to motivate ourselves to make better lifestyle choices is not easy, and we Americans have very effectively exported our bad habits to almost every other developed country. However, we do have some data about what has worked. Several factors are common among people who successfully make positive lifestyle changes:

They achieve “normals”—our term for satisfactory health metrics or health and wellness behaviors—on six indicators.* The healthiest bodies are the ones that meet the goals set by the six key indicators listed below. That’s why our barometer for health success is “6 Normals + 2”—normal scores on those six indicators plus two other factors: seeing a primary care physician and ensuring your immunizations are up-to-date.

Six key indicators of good health

Six key indicators of the optimal health status that promotes longevity:

1). Blood pressure of less than 120 mmHg systolic and less than 80 mmHg diastolic
2). BMI (a measurement of height-to-weight ratio) of less than 27 or, better, a waist-to-height ratio of 0.40 to 0.55
3).LDL cholesterol (a risk factor for heart disease) of less than 70 mg/dL
4). Fasting blood sugar (associated with diabetes) of less than 106 mg/dL
5). Urine free of cotinine (an indicator of tobacco use)
6).Completion of a stress management program

They use technology. The marketplace is full of all kinds of trackers that provide real-time feedback about our health choices. You can track steps, minutes of activity, heart rate, calories, sleep quality, and much more. While not everyone needs or likes these aids, technology can provide an excellent form of motivation by establishing benchmarks and goals. And it can help you try to reach those goals, especially when combined with the encouragement of a coach. The human touch is key to making the technology meaningful and the changes sustained.

They leverage financial incentives. It’s a basic human reaction: Significant financial incentives have always been a driver of behavior change. Much of the burden of establishing those incentives comes down to how our government and industries reward employees who stay or get healthy. You can improve your financial situation with better health, starting with lower medical costs, higher work productivity, a longer career, and less worry about the impacts of pandemic diseases too.

They have a buddy, or several. You need a built-in ecosystem with your own tribe—a community of people who support one another in pursuit of their goals. It can come in many forms: one person, a small group of people, or a large tribe with lots of people pursuing the same goals. Many of us may experience some combination of those supporters during the evolution of a wellness journey. Having a partner (or partners) in your pursuit of behavior change is the variable that most predicts success.

They do the little things that matter. Going into a hip replacement at age 59 and again at 64, co-author Peter Linneman was fit, did physical therapy before the surgery, and actively stuck with it after surgery; as a result, he was able to quickly and fully recover. Peter’s physical therapist noted that the scenario for most patients is to go into the surgery weak and ignore the post-op therapy. They blow it off, perhaps thinking it’s really not that important. This is the way a lot of us think about health: Why bother with the little things? Will they really matter that much? Yes! Every little decision adds up, and even more as you live longer.

Science is about to offer you the Garden of Eden. A chance not just at prolonged life but at prolonged youth—or rather, and even better, prolonged youthful years.

But taking advantage of it will be up to you.

Appendix L–Lifting Heavy Weights can Help you Mitigate Osteoporosis

In 2012, my aunt Susan Stuart-Jones, then in her late 50s, was diagnosed with osteoporosis—a finding that worried her. Her mother, who also suffered from the disease, had been an independent and adventurous world traveler, dancing in Morocco on her 80th birthday. But after breaking her hip she was confined to bed and a wheelchair and never recovered. Stuart-Jones’ grandmother also likely had osteoporosis, acquiring the nickname “Little Nana,” because she shrank so much in her later years—a classic manifestation of the bone-weakening disease.

To strengthen her bones Stuart-Jones, who lives in Sydney, Australia, followed mainstream advice to do exercise like walking, yoga, and other light weight-bearing activities. But it wasn’t enough. In early 2022, a DXA scan—the standard test to measure bone density—revealed a fracture in one of her vertebrae. “I’m thinking I’m crumbling,” Stuart-Jones told her physiotherapist who recommended a new and completely different strategy.

He prescribed lifting heavy weights, based on recent trials that showed women with osteoporosis women could gain bone this way. After getting the OK from her doctor, she started.

For decades, the conventional advice for people with osteoporosis was to engage in gentle exercises—but nothing too stressful. “Everybody had decided the way to manage osteoporosis with exercise was to just stop falling,” says Belinda Beck, a professor at Griffith University in Australia who has studied bone health for more than 20 years. Balance and stability exercises were prioritized, with the focus on preventing falls. But that kind of exercise doesn’t build new bone.

“Most of the literature shows that maintaining physical activity will stabilize bone mineral density, if not necessarily improve it,” says Kendall Moseley, a physician and the clinical director for the Division of Endocrinology, Diabetes & Metabolism at Johns Hopkins Medicine.

Beck saw patients with low bone density become “terrified to do anything because they’re going to break—so their life kind of closes in around them because they stop being as active. They can’t lift up their grandchildren, they can’t do things in the garden anymore,” says Beck.

Beck knew that even as we age, bone is responsive to exercise, and the basic principles of building bone are the same over a lifetime. Bone bends when you load it, and lightweight exercise doesn’t bend it much, whereas heavier weights do. That’s because although bone appears solid, it contains tiny holes that are connected via channels. When a bone bends, the fluid in the channels moves from the compressed side of the bone to the other side and pushes past the osteocytes—the stress sensors—and fires them up. This sends a signal to the osteoblasts to build more bone, says Beck.

This “very cool sensing system in the bone” is also the mechanism by which a broken bone heals. In those with low bone density, the key is ensuring that the loading is heavy enough to build bone slowly over time, but not so heavy that it breaks bones.

Challenging the norms of who lifts heavy

In 2013, Beck began a new study to measure the benefits of high intensity resistance and impact training, “which is what I knew bone needed to adapt.” She recruited 101 people over age 65 with low to very low bone mass; almost half diagnosed with osteoporosis based on their DXA scan scores. The randomized control trial included two groups: one did low-intensity supervised exercise (a protocol currently recommended by most doctors); the other group did heavier, supervised weightlifting. From prior studies, they knew that the bone remineralization takes at least 8 months, so that was the length of the study.

Their results showed that those in the heavy weightlifting group had significant increases in the density of the bones in their spines, while the low-intensity program participants continued to lose bone, “clearly showing low intensity doesn’t work to build bone, high intensity does,” says Beck. Moseley, who was not a part of Beck’s research, says the study is “very promising.”

Other physical criteria linked to decreased fracture risk also “improved compared to the control group,” says Beck. The result: lifting heavy weights reduced the risk of falling in addition to building back bone.

Beck formalized the protocol used in her clinical study, defining heavy weight as 85 percent of the maximum weight a patient can lift (which should increase over time). Since then, she has certified trainers in her program in eight countries, with practitioners reporting their results back to Beck. There are also independent physical therapists who are using Beck’s work as the basis for their own programs.

In New Jersey, Claudia Tamas, a doctor of physical therapy and the director of Women’s Health at Natural Medicine and Rehabilitation, received certification in Beck’s protocol and then worked with a group of women with osteoporosis for a year. When she compared before-and-after DXA scans, she found results consistent with Beck’s. Additional studies also supported Beck’s findings.

Lifting heavy weights is for middle-aged women too

Bone loss begins early, and there are several genes that are linked to the likelihood of osteoporosis, but lifestyle matters too. Women’s bone mass is greatest at around age 35, but due to sedentary lifestyles in modern cultures, that peak might be quite low (compared to cultures where women are doing physical labor). That’s because building muscle builds bone. According to Tamas, conversely, “muscle weakness and muscle loss is always going to be accompanied by bone loss.”

Tamas says she’s seen muscle weakness in women as young as their early 40s. But the decline is not inevitable. “Ideally, you want to start weight training in your 30s, so you can maximize that peak in bone density.”

In both men and women, bone density declines about 1 percent a year after age 35, but at menopause it declines by about 10 percent in a short period of time for women. Tamas points out that if you start at a higher bone density, losing some at menopause might not be a problem. But thinner bones from the get-go mean “When menopause comes, you’re already at the edge of the cliff,” says Tamas.

There’s always time to build back bone

The great news is that almost anyone, at any stage of life can build bone back through weightlifting programs like Beck’s. But this is an intensive, long-term exercise plan that must be done with supervision.

“The challenge is obviously in access and to know what to do and how to do it—and how to do it safely,” says Moseley.

Not everyone would be able to physically complete the exercises. Bone loss isn’t just caused by age, but by anything that causes chronic inflammation, as well as liver disease, kidney disease, organ transplant, and drugs taken for those issues that cause bone breakdown, like steroids, according to Moseley.

Still, Tamas says even one of her patients with an autoimmune disease is now maintaining bone—previously the patient had lost 5 percent a year.

Almost 20 percent of women older than 50 will become osteoporotic—that number is increasing—and half of them will suffer a broken bone due to low bone mass (osteopenia).

“People will go to the doctor and the doctor will say, Oh, you’ve only got osteopenia, you don’t need to worry but actually, that’s not true at all. You’re definitely at risk of fracture if you have osteopenia,” says Beck. Breaking bones doing normal life activities is a sign of risk.

“Falling from standing height and breaking something—that shouldn’t really happen,” says Moseley.

Stuart-Jones is now finishing up her first year of weightlifting at age 69, and she’s able to deadlift 125 pounds. Of course, she’s hoping her bone-mineral scans will show a bone density increase—but she’s also come to love weightlifting for its many other benefits. Besides losing 15 pounds, she’s gained muscle, reshaped her body, and her posture is noticeably straighter. Her confidence has improved along with her growing strength, something Tamas and Beck also noted with the groups of people they trained.

Lifting plant pots, putting laundry on a top shelf, and moving boxes during a recent move were all surprisingly easy: “I kept thinking, Oh, that might be a bit heavy, and then realizing, Oh, it’s not at all,” she says.

Resources

nationalgeographic.com, “Lifting heavy weights can help you mitigate osteoporosis. Here’s how to get started.” By Starre Vartan;

Appendix M–What is ‘Inflammaging’?

It happens to everyone. With age come discomforts: achy joints, wounds that heal more slowly, and a rising risk for cancers, heart disease, dementia, arthritis, and other illnesses. Those changes follow an uptick in inflammatory molecules over the course of a lifetime, according to a large and growing body of research. The link between age, inflammation, and disease is so well established, it has a name: inflammaging.

Now, researchers are unraveling the details of how the inflammatory process changes over the lifespan, what instigates the shift, and how it might be possible to interfere with the process. The work suggests interventions ranging from new drugs to new motivations for healthy habits like exercise that can slow the aging process, says Ron DePinho, a cancer biology and aging researcher at the University of Texas MD Anderson Cancer Center in Houston.

Research on inflammaging also illustrates the nuanced challenge of taking the reins of inflammation to sustain health later in life. Although many people fixate on the need to reduce inflammation, it is more important to sustain the appropriate amount of it as a means toward extending quality rather than quantity of life, says Judith Campisi, a cell biologist at the Buck Institute for Research on Aging, an independent research facility in Novato, Calif.

“What happens with age is you lose control of inflammation,” she says. “Even if you’re five years old, you will never heal a wound without an initial inflammatory response. It’s not always bad. It’s sometimes good.”

Hallmarks of aging

As people age, according to numerous studies, increasing amounts of pro-inflammatory cytokines and other inflammation-related molecules circulate in the blood alongside a rise in localized inflammation. When the shift occurs depends on the person, DePinho says, but 50 is generally when inflammation starts to increase, with a dramatic shift after 60.

That uptick tracks closely with disease trends. Beginning in the early sixties, risks rise substantially for the most common chronic diseases of aging: cancer, diabetes, heart disease and dementia, DePinho says. Starting at 65, the number of people with Alzheimer’s doubles every five years. In the U.S., 80 percent of adults over 65 have at least one chronic condition. By age 85, a third of people may have Alzheimer’s, while a third of men and one-fourth of women have had cancer. People with more inflammation in their bodies have a higher risk of disease.

Scientists have identified a dozen biological changes that correspond with age. All of those hallmarks of aging are associated with inflammation, and inflammation is considered a pillar of aging, says Luigi Ferrucci, a geriatrician and epidemiologist at the Intramural Research Program of the NIH’s National Institute on Aging in Baltimore, Maryland.

For example, as people get older, their immune cells lose their protective functions and stop doing the job of fighting off invaders, turning into what scientists call senescent cells. Other kinds of cells can also become senescent in response to stress. They cease replicating, no longer do their jobs, and start to secrete powerful inflammatory molecules that cause yet more cells to become senescent in a self-perpetuating cycle.

A relentless loop

Meanwhile, DNA damage inside cells accumulates over time, especially at the tips of chromosomes in protective regions called telomeres, which are long stretches of bunched-up DNA. Each time a cell divides, its telomeres become shorter until they reach a critical length that is perceived by the cell as DNA damage or instability, which may induce cellular senescence.

As telomeres become damaged, they initiate a signaling process through proteins that turn certain genes on and off. Some of the genes affected support the function of mitochondria (the cell components that produce energy). As a result of the gene disruption, mitochondria become defective and leak their DNA into cells, sparking inflammation.

Scientists used to consider telomere shortening, mitochondrial damage, inflammation, and other processes as separate theories of aging that could contribute to diseases like cancer, DePinho says. Now it is clear that all of these changes are connected and that inflammation acts like a “co-conspirator” in the aging process.

As chronic inflammation sets in, it becomes harder for the immune system to perform routine tasks, like detecting and eliminating cancer cells and pathogens, which could make people more likely to develop diseases. Inflammation in the body may also activate immune cells in the brain called microglia, according to one theory, causing inflammation, weakening the blood-brain barrier, and destroying nerve cells, ultimately contributing to the development of Alzheimer’s.

This burgeoning understanding of inflammaging as a relentless circuit of steps that all exacerbate inflammation is revealing new ways to break the cycle.

Aging better

Efforts to develop anti-aging interventions that target inflammation are challenging because they need to be specific to avoid causing more harm than good, Ferrucci says. Trying to tackle the chronic inflammation of aging with general anti-inflammatory drugs, for example, could make people more susceptible to disease by impairing the inflammation that our bodies need for staying healthy. “When you have an infection, if you don’t have inflammation, you’re going to die,” Ferrucci says. “Shutting down inflammation with a bomb like a corticosteroid or some monoclonal antibodies works. It’s also quite dangerous.”

One of the most promising new strategies for dealing with inflammaging is attacking senescent cells, experts say. In mice, a low-dose combination of two drugs, called Dasatinib and Quercetin, appears to be particularly effective at getting rid of these deadbeat cells and reducing inflammation in the intestines with the potential to extend lives. Clinical trials are now underway with these and other so-called senolytics to see if the same kinds of compounds might kill senescent cells and break the cycle of inflammation and disease in people too, says DePinho.

Other ongoing approaches include efforts to identify drugs that could restore telomeres, enhance mitochondrial function, and activate anti-aging genes, a strategy DePinho is working on. Some over-the-counter supplements claim to boost levels of proteins called sirtuins, which help cells respond to stresses, and a molecule called NAD+, which helps mitochondria function, among other roles, and dwindles in half from youth to middle age. Although evidence has been seriously questioned and these products have been over-hyped, DePinho says, further study may illuminate new anti-aging properties of sirtuins.

Scientists are hopeful that they are getting closer to understanding which interventions will help most, and studies in mice illustrate the tantalizing possibilities. “Tissues retain a remarkable capacity to renew themselves if you remove the underlying instigators of the aging process,” DePinho says.

Advances in immunology are lending new insights into how we can allow good inflammation to proceed while squashing the bad that can come from too much of it, Ferrucci adds. “As we discover the nuances of inflammation,” he says, “then it may be possible to find drugs that do not shut down inflammation completely.”

Age-fighting behaviors

For now, there are simple steps people can take to address inflammaging in their own bodies, experts say, including exercise. Regular physical activity enhances DNA repair, improves mitochondrial function, activates sirtuins, and, studies show, can reduce the risk of cancer, diabetes, heart disease, and Alzheimer’s. Regular vigorous activity is best, but as little as 15 minutes a day can make a difference, DePinho says, and even leisure activities help.

Dietary choices, too, can improve the chronic inflammatory state of inflammaging, according to a variety of studies that support eating a Mediterranean-style diet with an emphasis on whole grains, produce, nuts, and fish. Eating a wide variety of vegetables may also help sustain the gut microbiome, which tends to become less resilient and contribute to rising levels of inflammation with age. Each Saturday, when Ferrucci goes to the market to shop for the week, he buys 10 different kinds of vegetables, based on this emerging evidence. “That is something that has been suggested in the literature,” he says. “And I think that’s a simple way of following that advice.”

Body fat releases cytokines that promote inflammation, DePinho adds, so using exercise and diet to control weight can have extra benefits. He also advises people to avoid or quit smoking, a habit known to increase DNA damage and drive inflammation. Finding ways to relax is another useful goal, as chronic stress has been linked to shortened telomeres, accelerated aging, and inflammatory diseases. Adequate sleep and meditation can help reduce stress, DePinho says.

Healthy habits like these are important throughout life, Ferrucci says, but they become especially important as the mechanisms that protect our cells from damage become less functional with age. That accumulating damage is a key source of inflammation. “Intervening in any possible way becomes more important as you become older,” he says.

Resources

nationalgeographic.com, “What is ‘inflammaging’? Here’s how inflammation affects you differently as you age.” By Emily Sohn;

Appendix N–It’s not your Life Span you need to worry about. It’s your Health Span

We’re living much longer than our ancestors, but is that always a good thing?

With many people living well into our late 70s or beyond, more of us are also spending a greater portion of our lives—sometimes a decade or more—saddled with physical and mental health conditions that can make it challenging to accomplish the tasks of daily life.

Improving the quality of our twilight years is a growing area of inquiry among biologists and other longevity researchers who are working to boost the number of our disease-free years, a concept formally known as health span.

That term first showed up in medical journals more than 30 years ago, loosely defined as years free of disease, but the concept has become more mainstream among clinicians and patients alike, and its definition has broadened to focus more on the years without health conditions that would severely impede daily activities. Treated hypertension, for example, wouldn’t significantly affect health span, unlike a stroke or dementia, says Harvard Medical School physician-scientist Sharon Inouye, who focuses on aging issues.

The targets of researchers like Inouye are numerous: understanding the underlying mechanisms for aging, working to identify health-promoting genes, and zeroing in on steps we can take in our daily lives to improve our health span.

Genetic lessons from our 100-year-old elders

It’s certainly possible to live healthier even as we live longer.

Nir Barzilai says we can learn as much from looking at the health and longevity of the centenarians he works with at Albert Einstein College of Medicine in the Bronx, New York. In academic parlance, his healthy study participants have what’s called compression of morbidity—they’re sick for a very small portion of their lives.

“They don’t just live longer, they live much healthier—they got diseases 50 years after their friends and 30 years after their children’s friends.”

But how can the rest of us get there?

Some of those centenarians’ good luck comes from envy-worthy genetics. Studying their genetics is tantalizing, he says, since pinpointing which genes are linked to age-related disorders could lead to drugs that mimic their effects for those who weren’t as lucky in the genetic lottery.

Barzilai’s research has particularly focused on the genes that modulate our “good” cholesterol to help us stay healthier in a variety of ways. His centenarian study participants are much more likely to have a specific variant of the cholesterol-controlling CETP gene, and those patients tend to live longer with better brain function, he says.

Emulating that gene’s effects is now a target of ongoing research. With such drugs in our arsenal in the future, Barzilai says, humans can and will improve their health span—particularly if they follow current recommendations for modifying diet, exercise, and social interactions.

Lifestyle tips to live heathier, longer

Overall, the most cutting-edge developments when it comes to health span depend on your perspective, says Inouye, who also directs the aging brain center at Harvard-affiliated nonprofit Hebrew SeniorLife.

“If you talk with a longevity researcher, they will wax eloquent on the latest drugs being studied to enhance longevity—mostly in non-human models or animals at this stage,” she says, adding, “to me, the most important work in health span focuses on the importance of prevention.”

Eating a diet rich in fruits and vegetables and low in carbs is important, Inouye says, alongside keeping mentally active and socially engaged with activities like volunteering, regular aerobic and strength exercise, and avoiding tobacco and excess alcohol. Recent research in JAMA Internal Medicine, where Inouye serves as editor in chief, shows that diet, exercise, brain games, and other steps can significantly help preserve brain health.

Good sleep also remains essential, even if it’s something you need to continually work on, adds geroscientist Matt Kaeberlein, formerly of the University of Washington and now CEO of the Seattle-based biotech Optispan. Poor sleep increases the risk of developing numerous disorders including type 2 diabetes, high blood pressure, heart disease, poor mental health, and even early death, according to the U.S. Centers for Disease Control and Prevention.

(How scientists are unlocking the science of sleep.)

The broad strokes of a healthy diet are well-documented, but different strategies may work better for certain individuals, Kaeberlein adds. Whether it’s a Mediterranean diet, which is high in fruits, veggies, and whole grains, or approaches like intermittent fasting or a low-carb, high-fat ketogenic diet, Kaeberlein says, there should always be a focus on what feels right for you.

What do longevity researchers do for themselves?

Scientists steeped in the latest research on the biology of aging don’t all adopt the same lifestyle choices themselves, and some even make personal choices that step outside the bounds of what the U.S. Food and Drug Administration has approved, which may come with some unknown risks.

At age 68, Barzilai’s health regime includes daily exercise, intermittent fasting, good sleep, maintaining social activities, and taking a widely prescribed diabetes drug called metformin that some aging researchers believe attenuates age-related diseases. In animals, the drug appears to work partly by improving the body’s response to insulin with knock-on effects for cellular aging and combating cognitive decline. Barzilai says he takes the medication off-label since the FDA hasn’t approved the drug to specifically treat aging.

Kaeberlein, who’s in his 50s, has turned to a different off-label medication, an immunosuppressant called rapamycin that was originally approved by the FDA for organ transplant patients. When taken in low doses, Kaeberlein says it essentially tricks cells into turning down growth-promoting signals and turning up stress resistance, which then seems to halt or even reverse cognitive and functional declines in animals. His research as co-director of the long-term Dog Aging Project and other work in animals suggests that it shows promise: In mice, for example, the drug can expand life spans by as much as 60 percent.

But results in rodents often are not replicable in humans. Moreover, since these drugs aren’t yet approved for age-extending use in humans, the data on potential long-term side effects in otherwise healthy people remains unknown.

People should weigh the risks and benefits of taking any medication and decide what makes sense for them in consultation with their doctors, Kaeberlein says.

Get to know yourself better

Beyond experimental drug approaches, Kaeberlein says a lot of progress in this space could simply come from better self-monitoring with more baseline health data about our own vitamin deficiencies, hormones, and blood sugar, among other factors.

Asking your doctors to measure those baseline indicators in your 30s or 40s could better inform what actions to take later in life and let you know if urgent interventions are needed, Kaeberlein says, though he notes that often such testing isn’t covered by health insurance in the United States.

Simply popping a daily multivitamin to stave off or address unknown vitamin deficiencies is not a good idea, he cautions, since it doesn’t allow people to know if they truly had deficiencies—and, if they do, multivitamins may not have the appropriate level of supplements to address an individual’s specific need.

Make friends and calm your mind

Another key pillar for expanding your health span is connectedness with one another and with yourself. Even if you routinely interact with at least one person that you live with, like a spouse, other social relationships and experiences remain important in our old age.

“Right now, without taking any drugs, we can basically maximize our exercise, our nutrition, our sleep, and our social connectivity. Those are the four things that anybody who wants to can do,” says Barzilai.

Activities like joining a walking group or joining a group focused on hobbies you already enjoy can make us healthier, according to the National Institute on Aging. Unsurprisingly, the benefits are myriad for mental and physical health, and may include lowering risk of dementia, heart disease, and stroke.

When we’re out in the world, even if it’s just walking our dogs (assuming we avoid falls), it also increases happiness and exercise. Volunteering, tutoring, or other meaningful activities that keep our brains active and involve social interactions as well can be personally fulfilling, and are linked to improved memory and reduced stress.

“Even if you struggle with interpersonal relationships,” Kaeberlein says, you can also focus on inner peace and wellness. Some people find meditation and mindfulness practices quite useful even if you don’t have the interpersonal connection dialed in, he says.

People who have a great mindfulness regimen should still try to make friends, he says. “I’m trying to work at it, and I think it takes effort for some people who have neglected it in life,” he says. “There’s a lot to be gained from rebuilding those relationships.”

Resources

nationalgeographic.com, “It’s not your life span you need to worry about. It’s your health span.” By Dina Fine Maron;

Appendix O–How Old are you, Really?

Using a 3D camera system and artificial intelligence, Jing-Dong Jackie Han, a researcher at Peking University, has developed a system that can determine a person’s physiological age. This heat map—red (higher values along the x, y, and z-axis) and blue (lower)—indicates how an average Han Chinese woman’s face changes with age. Physiological age can differ from chronological age by as much as 7.5 years (average of top 5% outliers).

A picture is worth a thousand words. But when that picture is a high-precision 3D image of the face, it might be worth a thousand blood tests as well. That’s because those full cheeks and under-eye bags are not just unsightly harbingers of age, but also a reflection of our health.

Scientists have known for decades that chronological age—a number that can be gleaned from our driver’s license-–doesn’t tell the whole story. Our so-called biological age, influenced by everything from our environment to diet and exercise habits, reflects the health of our cells and organs and can differ from chronological age by years. But unlike tracking the time we’ve been alive, biological age is more slippery to pinpoint. Now Jing-Dong (Jackie) Han and colleagues have developed an AI-driven process, dubbed a facial aging clock, that takes a 3D image of a person’s face and calculates their biological age.

A woman’s face as it ages from 20, left, to 65, right, as predicted by Han’s model. Han’s research indicates that accelerated facial aging is an indicator of systemic inflammation, and is associated with various health challenges such as high cholesterol, hypertension, and other aging-related diseases. This system is being used in clinics in China to assess patient health.

Inspired by a centuries-old Chinese practice, in which practitioners divine a person’s health by “reading” their face, Han, a computational biologist at Peking University, and her team constructed their clock by analyzing 3D facial images of approximately 5,000 residents of Jidong, China. The researchers created two AI-derived clocks—one that predicts chronological age and another that predicts biological age. These facial aging clocks track the changes our visages undergo with time: The corners of the eyes droop, the nose widens, the jowls sag, and the distance between the nose and mouth increases. And certain facial characteristics are known to align with certain ailments. Systemic inflammation, for example, shows up in sagging skin.

According to Andre Esteva, the founder and CEO of a medical AI start-up in Los Altos, California, Han’s work has the potential to upend preventative medicine: “If you could take a photo and get back your biological age, that could really influence your lifestyle.” With this tool, physicians could also track and manage the care of patients undergoing onerous treatments known to prematurely age people, such as chemotherapy. And it has potential to aid research into aging too.

“We’ve been getting so many requests from companies that want [our tool] to assess their supplements or anti-aging drugs’ efficacy,” Han says.

AI models require examples where the right answer, or “ground truth,” is already known to learn how to see it in new data—a face paired with the subject’s age, for instance. So, a potential sticking point arose: There is no gold standard for biological age. “The concept of biological age is more of an umbrella term for all the multisystemic things that occur with age,” explains Christopher Bell, who studies the relationship between age and chronic diseases at the University of London. From the shortening of our telomeres—the caps that keep our chromosomes from degrading—to the winding down of our mitochondria to the weakening of our immune system, it’s a challenge to choose just one aging marker.

The first clocks to measure aging were based on changes in patterns of methyl groups—chemical tags added to DNA that switch genes on and off. This DNA methylation machinery that regulates gene activity deteriorates over time. The pattern of this deterioration—which areas in our genome are affected—can tell us how fast our cells and tissues are aging. Other clocks assessing age are based on protein distribution in the blood or the number of times stem cells have divided.

Facial aging clock

Han decided in 2016 that she wanted to use another measure—perceived age, or how old you appear to others. She was inspired by a 2009 study in which volunteers assessed the age and health of twins in a photograph, followed by a medical evaluation of the subjects seven years later. Those researchers found that the older-looking of a twin pair was more frail, cognitively impaired, and likely to have died compared to their younger-looking sibling. Clearly, Han thought, biological age, as proxied by appearance, is strongly correlated with health. Her group had already incorporated 3D images of faces in research published in 2015, in which they found that facial features could predict chronological age in a statistical model developed using 300 subjects from Beijing.

At the time, she had been investigating markers, or signatures, in the blood and ascertaining their relationship to age when she noticed that the Chinese Academy of Sciences-Max Planck Society Partner Institute for Computational Biology, where she then worked, had a 3D facial imager. She thought, since they had this imager, they should take it with them when they collect blood samples and use it to compare what the face reveals about aging versus what the blood markers reveal.

By 2016, she had access to a larger cohort, approximately 5,000 people from the city of Jidong, and more powerful AI techniques. With the data-crunching prowess of AI, Han could replicate human perception of how biological age manifests in someone’s face. To minimize fluctuations from any one observation, in Han’s new study, each subject’s biological age was assessed independently by five volunteers and served as the “ground truth” for training the AI.

The AI engine, which learned from and improved on these human observations, was startingly accurate. On average, its predictions deviated from actual ages by about three years for both chronological and perceived age models. In Han’s study, people who appeared more than three years older than the date on their birth certificate she dubbed fast-agers; while slow-agers seemed more than three years younger.

This difference between their predicted and actual ages can be correlated to various health parameters, Han says. And according to Han, these outliers teach us the most about how we age.

To explore the links between appearance, age, and the underlying factors that influence health—Han collected blood samples and surveyed the habits of the research subjects. For example, smoking, snoring, and high levels of total cholesterol in the blood were often characteristics of fast-agers whereas yogurt consumption, regular mealtimes, and greater bone mineral density were a common trait of slow-agers.

Middle age, when individuals are in their 40s and early 50s, seems to be a period when the differences between fast- and slow-agers become more noticeable. Some people might look quite old even though they’re just 40 while others are 55 but still look very young. According to Han, this variability means that interventions to adopt healthier habits could make a significant difference in this window of opportunity.

Han and her collaborators also constructed additional models to examine the underlying molecular mechanisms behind aging and match them to facial features of fast-agers through the AI-derived clocks. For example, they developed clocks which identified active genes in blood from an older-seeming individual, and matched them to the facial features of the same individual.

For those predictions that overlap, researchers can ascertain which genes (and therefore molecular pathways) are turned on for older faces compared with younger faces. For all clocks, “accelerated aging is highly associated with infections and inflammation,” which manifests in the face as a narrowing of the forehead as the skin sags, says Han. On the other hand, high LDL and total cholesterol levels in the blood translates to full cheeks and undereye pouches.

Applications of the technology

Aging research has become mainstream, but one of the field’s problems has always been: We don’t know exactly what biological age is, nor is there an objective way to quantitatively define it. But according to Ruibao Ren—a physician-scientist at the International Center for Aging and Cancer at Hainan Medical University in China—Han’s research, as well as ongoing work in other labs, has made great strides to narrow this information gap.

“Just being able to measure aging is already a big leap forward and Dr. Han’s technology—already in use at the hospital he works at in Hainan—will play an important role in aging studies,” Ren says. Pharmaceutical companies can employ the tool to assess drugs that promote longevity or slow down aging, for example. And as an oncologist, Ren hopes that with the facial clock, he can diagnose cancer patients while the disease is in its early stages. Since cancer is strongly correlated with age, if someone shows signs of accelerated aging, doctors can be more proactive with screening. “Aging is at the root of probably 80 percent of diseases,” Ren says.

Doctors could also incorporate biological age as one of the panel of tests included in your annual physical like cholesterol tests or blood pressure measurements. “It could be a wake-up call that asks: How are you doing with managing your health?” Ren says.

And unlike other clocks which require blood or tissue samples and expensive analysis to implement, the facial clock is comparatively economical and non-invasive, requiring the patient to sit for just one minute in front of a 3D imaging camera.

Future directions

Bell too sees great potential in the further study of aging clocks, especially as datasets become larger. The earliest epigenetic clocks, for example, looked at 1,500 potential methylation sites on our DNA, while the most recent clocks consider more than 900,000. But aging clocks’ real power, Bell says, is their potential to uncover novel insights into the aging process.

He highlights, for instance, how abnormal DNA methylation is a signature of cancer as well as aging. By understanding both scenarios, “we might identify novel therapeutic avenues to treat these diseases,” Bell says.

But he counsels caution in interpreting the results from various aging clocks. “At a population level, these clocks are capturing some aspects of aging.” On an individual level, however, there’s more work to be done. “If we measure someone’s particular epigenetic clock age, we can’t be as confident of how well that tracks in that individual or that changes over time represent reality.”

As for Han, her team continues to explore other clocks such as a transcriptome clock, which reflects DNA damage in the blood, and a single cell clock, based on information from one cell. The aim is to aggregate disparate measures—each clock showcases a different aspect of aging—into a composite clock. They also continue to refine their facial aging clock—a version applicable to all ethnic groups will be published soon.

What is Han’s ultimate goal? “Well, I’m telling my colleagues that I will try to make them live at least five years longer—and look at least five years younger,” she laughs.

By reading a “signature” based on 150 of a person’s genes, researchers can determine the individual’s biological age, which may be different from his or her chronological age, according to a new study.

Moreover, a person’s biological age is a better measure for determining a person’s health than is chronological age, these researchers say. In the study, people’s biological age was more closely tied to their risk of age-related diseases, such as dementia and osteoporosis, than was their chronological age.

“Most people accept that all 60-year olds are not the same,” James Timmons, a professor of precision medicine at King’s College in London and the lead author on the study, said in a statement. But a person’s chronological age is still used to determine everything from the individual’s insurance premiums to whether he or she needs certain medical procedures, he said.

In the new study, published today (Sept. 8) in the journal Genome Biology, the researchers analyzed genetic material from healthy 65-year-olds, looking for genes that indicated the participants were staying healthy as they aged.

The scientists found 150 genes that they used to calculate what they called a person’s “healthy age gene score.”

To verify that these scores did indeed track with people’s health, the researchers tested out their method in a separate group of participants, who were all 70 years old. The scientists found that higher scores were indeed associated with better health, including better cognitive health.

In particular, they found that patients diagnosed with Alzheimer’s disease had lower healthy age gene scores.

“This provides strong evidence that dementia in humans could be called a type of ‘accelerated aging’ or ‘failure to activate the healthy aging program,’” Timmons said.

It unclear, however, whether the healthy age gene score could be used to predict whether a person will develop Alzheimer’s disease, the researchers wrote in the study.

That’s “the real Holy Grail,” said Keith Fargo, director of scientific programs and outreach at the Alzheimer’s Association, who was not involved in the study, “a blood test that tells you 10 years in advance if you’re going to have Alzheimer’s.”

Still, the results of the study are valuable, Fargo told Live Science. The researchers were able to look at people who were all the same age, and determine who had healthy cognition and who didn’t, he said. That means the test could help determine what genetic differences separate a 70-year old with Alzheimer’s and a 70-year old without the disease, he said.

Further researcher into those 150 genes may also give clues about what causes Alzheimer’s, Fargo said.

Resources

nationalgeographic.com, “How old are you, really? The answer is written on your face..” By Connie Chang;

livescience.com, “How Old Are You Really? Genes Reveal ‘Biological Age’.” By Sara G. Miller;

Appendix P– Can Aging Be Cured?

Seconds after his birth, Tommaso Citti has his vital signs checked at Beauregard Hospital in Aosta, Italy. Children born today in prosperous countries are very likely to live into their 90s. As the world grows significantly older, research into slowing or reversing aging becomes more and more important.

As promised I would keep updating my aging section of this blog. When I get enough extra material, I will create a second edition for book “Aging Really Sucks!”, with a part devoted to anti-aging. This particular article was copied from an online article from nationalgeographic.com and was written by Fran Smith. I do not make any money from this blog nor do I make any real profits from my books. The money made goes towards paying my expenses to produce the material. It costs me several hundred dollars a year to just maintain my sites, and to do the research. A lot of the sites that I pull information from are paid sites. On my posts I try to bring together material from diverse sources, I shift through the crap and in most cases I do not include my biasis in the articles, I allow the reader to decide for themselves. I hope you find the information that I provide helpful.

Can aging be cured? Scientists are giving it a try

Cutting-edge technologies are revealing the intricacies of human aging and sparking research into drugs to slow it, or even reverse it.

Scientists are great at making mice live longer.

Rapamycin, widely prescribed to prevent organ rejection after a transplant, increases the life expectancy of middle-age mice by as much as 60 percent. Drugs called senolytics help geriatric mice stay sprightly long after their peers have died. The diabetes drugs metformin and acarbose, extreme calorie restriction, and, by one biotech investor’s count, about 90 other interventions keep mice skittering around lab cages well past their usual expiration date. The newest scheme is to hack the aging process itself by reprogramming old cells to a younger state.

“If you’re a mouse, you’re a lucky creature because there are a lot of ways to extend your life span,” says Cynthia Kenyon, a molecular biologist whose breakthrough work decades ago catalyzed what is now a research frenzy. “And long-lived mice seem very happy.”

What about us? How far can scientists stretch our life span? And how far should they go? Between 1900 and 2020, human life expectancy more than doubled, to 73.4 years. But that remarkable gain has come at a cost: a staggering rise in chronic and degenerative illnesses. Aging remains the biggest risk factor for cancer, heart disease, Alzheimer’s, type 2 diabetes, arthritis, lung disease, and just about every other major illness. It’s hard to imagine anyone wants to live much longer if it means more years of debility and dependence.

To understand aging, researchers look for clues in animals, such as those studied by the 51-year-old Amboseli Baboon Research Project (ABRP) in Kenya. As part of that work, Benard Oyath and Jackson Warutere prepare to take blood and other samples from Olduvai, who was tranquilized and then released back to the wild. The project’s scientists have found that baboons with strong social connections in adulthood can recover from harmful health effects of a stressful childhood.

But if those mouse experiments lead to drugs that clean up the molecular and biochemical wreckage at the root of so many health problems in old age, or to therapies that slow—or, better yet, prevent—that messy buildup, then many more of us would reach our mid-80s or 90s without the aches and ailments that can make those years a mixed blessing. And more might reach what is believed to be the natural maximum human life span, 120 to 125 years. Few people get anywhere close. In industrialized nations, about one in 6,000 reaches the century mark and one in five million makes it past 110. The record holder, Jeanne Calment in France, died in 1997 at 122 years, 164 days.

Human biology, it seems, can be optimized for greater longevity. Unimaginable riches await whoever cracks the code. No wonder investors are pouring billions into trying. Google led the spending spree with the 2013 launch of Calico Life Sciences, where Kenyon is the vice president of aging research. Over the past few years, investment in the industry has come from tech tycoons, overnight crypto millionaires, and most recently Saudi royals. It seems everyone with cash to burn is placing a bet on aging’s next—or really, its first—big thing.

This work is powered by artificial intelligence, big data, cellular reprogramming, and an increasingly exquisite understanding of the zillions of molecules that keep our bodies humming. Some researchers even talk about “curing” aging.

Humans have chased dreams of eternal youth for centuries. But the study of aging and longevity was such a scientific backwater as recently as 30 years ago that Cynthia Kenyon had trouble recruiting young researchers to assist her in the experiments that would break the field open. Working then at the University of California, San Francisco, she altered one gene in tiny roundworms known as C. elegans and doubled their life span. The mutants acted younger, too, slithering friskily under the microscope while their unaltered peers lay about like lumps.

Kenyon’s startling discovery showed that aging was malleable—controlled by genes, cellular pathways, and biochemical signals. “The whole thing shifted from being out there in the nebulous world to familiar science that everyone understood,” she says. “And everyone could do it. So people just moved in.”

Delaying death in worms and mice, however, doesn’t mean it will work in humans. For a hot minute, senolytics, which kill damaging cells that accumulate with age, appeared poised to become the first antiaging therapy to make it through the regulatory gauntlet. But one of the first clinical trials, a highly anticipated study of an osteoarthritis treatment, found that it didn’t reduce swelling or joint pain any better than a placebo. Researchers and biotech companies are now testing senolytics to treat early onset Alzheimer’s, long COVID, chronic kidney disease, frailty in cancer survivors, and a complication of diabetes that can cause blindness. Clinical trials of other antiaging compounds are also under way. But so far, none of the experimental drugs that have had such dazzling effects in mice have made it to the market.

“There are lots of different approaches,” Kenyon says. “We don’t know if any of them will work. But maybe they’ll all work! Maybe combinations will be fabulous. The good news now is that people have literally accepted this kind of science as being real. They’re excited about the possibilities. We just have to try a lot of things. And that’s what people are doing.”

Walt Crompton, a retired biomedical engineer in Silicon Valley, is 69 years old. He has ample white hair, a white goatee, and a dark vision of growing older. “I’m at the age where I’m swirling around faster and faster at the bottom of the toilet,” he says. “You look around, more and more of your peers are dying, getting horrible diseases. You have little aches and pains, all of a sudden your knee hurts when you run, and blah, blah, blah. If it’s not one thing, it’s another.”

With a mindset like that, it’s no surprise Crompton became obsessed with aging and life-extension research. He read the mouse studies. He helped out at a longevity lab. He attended conferences where scientists spoke of the “hallmarks” of aging, the interconnected ways that biology goes awry over time.

Protective caps on chromosomes, called telomeres, shorten. The genome becomes unstable and cancer-causing DNA mutations increase. Changes occur in the epigenome—compounds that latch onto DNA and regulate the activity of genes. Some cells become senescent, meaning they stop functioning normally, but like zombies, they don’t die, and they secrete chemicals that cause inflammation. Disruptions occur in pathways that respond to nutrients, lipids, and cholesterol, throwing metabolism out of whack. And the list goes on. There’s no consensus on how these changes influence one another, or which is the most important to address.

At a conference, Crompton heard a scientist named Gregory Fahy explain his theory that immunological aging could be reversed by treating the thymus, a small gland in the chest that stimulates the development of disease-fighting T cells. Fahy was seeking volunteers to test his idea that injections of recombinant human growth hormone, a drug used for decades to treat children with short stature, could rejuvenate the thymus and the body’s waning defenses against disease. Fahy had injected himself with the stuff on and off for eight years, and with his thick dark brown hair and youthful enthusiasm, he appeared in enviable shape for a guy of Social Security age. Crompton signed up.

Fahy, the chief scientific officer of Intervene Immune, a California-based company, is well known as a cryobiologist who developed a technique to preserve kidneys by infusing them with ethylene glycol and storing them at minus 135°C (-211°F) until they can be transplanted. He created a stir by rewarming a rabbit brain in near-perfect condition, raising hopes a way will be found to allow mammalian brains, ours included, to survive cryopreservation. But Fahy has been fascinated by the thymus for decades, since he read a study by scientists who refreshed the immune systems of rats by implanting cells that make growth hormone. He believes most drugs that extend mice lives will disappoint us, because they “don’t do anything about keeping your immune system from going south.”

Recombinant human growth hormone is off patent, so repurposing it for antiaging won’t yield the financial bonanza of a new drug; it’s also associated with an elevated risk of some cancers. Fahy tried to get other scientists interested in doing a clinical trial and failed. “I took matters into my own hands and started regenerating my own thymus based on what I could glean from the rat study,” he says.

Because the drug can raise the risk of type 2 diabetes, he added two pills: metformin and dehydroepiandrosterone, or DHEA, a hormone that improves blood-sugar regulation. Both are also thought to mitigate the effects of aging, and they’re commonly used for that purpose. Metformin, which is taken for diabetes by 150 million people worldwide, may reduce the incidence of neurodegenerative diseases and cancer. U.S. researchers are planning a study to see if it prevents or delays major age-related illnesses. But some longevity scientists aren’t waiting: They pop metformin daily.

Crompton says he immediately felt the effects of Fahy’s regimen. “It seemed like I could leap tall buildings in a single bound.” He shed unwanted pounds without dieting. Another participant, Hank Pellissier, 70, tells me his hair, previously white, began growing in brown.

Tests showed that T cell production increased with the treatment, thymus fat disappeared, and kidney and prostate health improved. Most striking, the men lost an average of two and a half years of biological age, as measured by what’s known as an epigenetic clock. It uses blood to measure chemical changes to DNA that alter gene expression and mark the passage of time.

Fahy’s study, published in 2019 in the journal Aging Cell, was too small to prove anything, and it was not placebo controlled. Nevertheless, the experiment provided the tantalizing suggestion that a medical intervention might lower a person’s biological age. Steve Horvath, who developed the epigenetic clock that’s now a go-to tool in longevity research, was impressed. The 55-year-old geneticist and biostatistician is now a participant in the larger trial Fahy is conducting.

Fahy, who is 72, enrolled as his own guinea pig and resumed his hormone injections. “I’m getting up there, unfortunately,” he says. “The clock is ticking. I have to do my work fast to save not only everybody else but myself as well.”

At 98, my mother, Dorothy, has outlived my father, her two younger sisters, and a late-life boyfriend. Her short gray bob is always salon perfect. She is thin and walks slowly, with a cane, but she stands straight. On most weekdays she goes to her neighborhood senior center, where she takes exercise classes, dances, and eats lunch with friends. She never forgets a birthday or a bill due.

Not much about her lifestyle would have predicted such healthy longevity. She escaped Nazi Germany as an adolescent, suffering more than her share of trauma, though I’ve never heard her use that word. She smoked cigarettes for decades. My father was a butcher, and we lived on red meat. On the plus side, she has always been physically active. She ran competitive track as a child, walked a few miles back and forth to work, and swam several times a week for years after she retired.

Scientists study healthy elders like my mother and track centenarians to figure out how they manage to defy the actuarial tables. Kristen Fortney, a 40-year-old biotech executive with a Ph.D. in medical biophysics, is putting big data and computational wizardry to the task. Most drug development for aging aims to fix something that goes wrong; Fortney is trying to understand what goes right.

“I’ve always approached it from the perspective of what’s going to have the greatest impact and what’s the low-hanging fruit,” Fortney says. “I’ve always believed that’s to copy what already works. There are already all these human examples of successful aging … individuals out there who are making it to a hundred and beyond, and their muscles still work, their brains still work, so we know it can be done.”

Fortney’s company, BioAge Labs in Richmond, California, analyzes blood and tissue stored in biobanks from Hawaii to Estonia. The specimens are linked to electronic medical records, so Fortney and her colleagues know the health outcomes of the people behind every vial of blood, and they search for biomarkers that distinguish those who’ve aged well. Machines measure each sample for up to tens of thousands of variables, including 7,000 proteins. (A decade ago, the best technology could pick out only a few hundred.) Using artificial intelligence, the scientists then identify possible targets for medication and search the reject piles of pharmaceutical companies for drugs that were developed for other purposes and shown to be safe but never released.

Fortney’s team has tested several dozen drug candidates in mice, and has two in clinical trials. One targets the immune system, and the other addresses muscle mass and strength. Because the U.S. Food and Drug Administration approves drugs only if they prevent or treat a disease, and the agency doesn’t consider aging a disease, trials such as Fortney’s investigate a drug’s effect on an age-related condition. But the researchers almost always have grander ambitions.

For example, Fortney is evaluating a compound, code-named BGE-117, for age-related muscle dysfunction because it acts on a pathway involved in tissue regeneration, remodeling blood vessels, and other critical processes. But the hope, the company explains, is to target “multiple diseases of aging with large unmet needs, high prevalence, and huge markets.”

It was feeding time when I visited Vera Gorbunova’s super-agers: 300 naked mole rats, give or take—a litter had been born four days earlier, and one pregnant female looked ready to burst. The refrigerator held bountiful options, including five pounds of apples, 18 ears of corn, two pounds of celery, three bags of romaine lettuce, purple grapes, bananas, white potatoes, sweet potatoes, and carrots, all of it organic.

Naked mole rats can live more than 40 years in captivity, 10 times longer than typical for a rodent their size. I couldn’t help thinking we’d all live longer if we just ate what these small, wrinkled, bucktoothed creatures do. Gorbunova and Andrei Seluanov, who are married and both biologists at the University of Rochester, study naked mole rats in hopes of stealing their longevity adaptations for us. “In every long-lived animal we find something new. Crazy things!” Gorbunova tells me.

The mystery of the phenomenal longevity of some animals has propelled studies around the globe. Researchers have endured Arctic storms and seasickness to catch, study, tag, and release Greenland sharks, which live at least 250 years and maybe even a few centuries more. Scientists dredging ocean quahog clams from the seabed north of Iceland hauled up a 507-year-old. University of Birmingham biologist João Pedro de Magalhães, seeking clues in DNA, sequenced the genome of the bowhead whale, a 120,000-pound behemoth thought to be the longevity champion of the mammalian world but endangered by pollution and other threats. He also worked with Gorbunova and Seluanov to investigate the naked mole rat genome.

The rodent habitat in Rochester, New York, is 90 degrees, dark, and humid, like a burrow. Each colony—a queen, her consorts, and many generations of her minions—inhabits its own plexiglass dwelling. It has wide tubes connecting three large canisters, ostensibly for sleeping, eating, and excreting. If naked mole rats don’t like a meal, says Nancy Corson, who manages the colonies, “they’ll put it in the toilet.”

They look adorably social as they somersault over one another and huddle in piles like laundry, but they’re belligerently territorial. Researcher Rochelle Buffenstein, who once had more than 7,500 and now has 2,000 in her lab at the University of Illinois, Chicago, has found the old don’t die any more often than the young. “Many of them die because they fight,” Gorbunova says. “That is not age dependent.”

Gorbunova showed me the other residents in her lab: Damaraland mole rats; Chilean rodents called degus, a model for studying Alzheimer’s; and African spiny mice, which have almost mythical powers to regenerate skin and cartilage. A large freezer is packed with tissue from squirrels, rabbits, porcupines, beavers, wild mice, bats, and two dozen other species. She gets these specimens from exterminators, hunters, animal-control officers, state conservation employees. She also traps some. And Wolfy, the family German shepherd whose framed portrait is displayed in her office, deposits the occasional carcass on her doorstep. I winced at that. “They served science,” she assures me.

Bowhead whales have more than a thousand times the cells we do, which should dramatically increase their risk of a cancer-causing mutation. But they don’t get cancer. Studies have shown they are astonishingly efficient and accurate at repairing DNA and keeping cells healthy. Gorbunova has found that other long-lived animals, including naked mole rats, share this superpower.

Bats control inflammation so masterfully they can harbor viruses without getting sick, a feat that drew global attention after they were suspected as the source of the pandemic’s coronavirus. “We were interested in bats even before COVID,” Gorbunova says. Scientists estimate that chronic inflammation, which often progresses as we age, is a major factor in more than half of all deaths worldwide.

And naked mole rats? One of their antiaging marvels is hyaluronan, a gooey sugar secreted by connective tissue. We make the substance, too, and it’s a staple of “age defying” skin creams. But Gorbunova and Seluanov discovered that the naked-mole-rat version has a different, heavier, molecular structure from ours, it’s much more abundant, and it doesn’t degrade as much as ours does. (And she told me, to my disappointment, that it’s produced differently from the pricey products I slather on my face.) Hyaluronan in naked mole rats not only makes their skin supple enough to squeeze through cramped tunnels but also suppresses tumors, the biologists found.

Studying longevity inevitably makes scientists contemplate their own. Once they pass a certain age, many do something—or a lot of things—to stave off molecular damage. Gorbunova, who is 51, tells me she eats seaweed because it activates a protein, sirtuin 6, which aids DNA repair and genomic stability. It struck me as on-brand that a biologist whose ringtone is a barking dog, and who says she chose her specialty because “I like animals and everything you can learn from them,” would try to enhance her own longevity by consuming fish food.

Gorbunova doesn’t study humans, though we’re considered long-lived animals too. We outlive all other primates, and not only because they’re more likely to be eaten by lions. Within a generation, Gorbunova believes, we’ll have treatments that extend the human life span by a decade or two. To push beyond that would require fundamentally changing the human operating system, and that may not be as wild as it sounds. “I think it’s possible,” she says.

In 2006, Shinya Yamanaka, a stem cell researcher in Japan, figured out how to reprogram adult cells and return them to an embryonic-like state. The discovery revolutionized cell biology and the search for ways to treat human diseases, winning Yamanaka a Nobel Prize. Now researchers are determined to use the technique, called cellular reprogramming or epigenetic reprogramming, to reverse aging and eradicate the illnesses that come with it.

“The implications could be bigger than CRISPR,” says biologist David Sinclair, referring to the transformative gene-editing technology. “I’m going to get destroyed for saying that! It’s certainly the biggest thing since CRISPR in terms of the amount of money and people getting into it.”

A group of high-profile tech entrepreneurs, including Jeff Bezos, shook the tight-knit world of aging research in early 2022 with the launch of a three-billion-dollar reprogramming venture, Altos Labs. Yamanaka signed on as an adviser, and other superstar scientists were lured from prestigious academic posts. Depending on your point of view, the massive investment in a technology that is itself embryonic either epitomizes Silicon Valley hubris or marks a shrewd bet on the future of medicine. “People will not invest serious money unless the science is believable,” says Steve Horvath, who retired recently from the University of California, Los Angeles to join Altos. “So the question is, will you and I benefit?”

Yamanaka used four proteins known as transcription factors, which initiate and regulate gene expression, to erase the identity of mature cells—essentially rewinding them to their original state. The leap to apply it to aging came from Juan Carlos Izpisua Belmonte, a biologist studying organ regeneration. He wanted to use the Yamanaka factors to turn back time only partway, restoring the youthful resilience of cells while maintaining their identity and function.

He and his team at the Salk Institute for Biological Studies in La Jolla, California, experimented with mice for several frustrating years until they hit upon a protocol that rejuvenated the animals instead of killing them. They used partial reprogramming to extend the lives of prematurely aged mice and to accelerate healing in normally aged old mice with muscle injuries. At the time, Izpisua Belmonte said the experiments demonstrated that aging “may not have to proceed in one single direction.”

Now, as a scientific director at Altos, he no longer talks publicly about turning aging into a two-way street. The company insists it is not in the business of reversing aging but of reversing disease. Maybe the backers want to distance themselves from the long, dubious history of antiaging snake oil, or they have their sights on what the FDA will approve: treatments for diseases, not for aging. But I was not the only one to puzzle over their distinction.

“What’s the difference?” Sinclair says, rolling his eyes.

Sinclair, a professor of genetics and co-director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School, makes no secret of his mission to thwart aging, including his own. He has founded and invested in more than a dozen companies to commercialize longevity technologies and molecules. At 53, he takes metformin and sprinkles resveratrol on his breakfast. “I try things once, at least, that people are talking about,” he says. “I’m curious. I like to be an experimenter.” He lifts weights to keep his hormone levels up—he posted on Instagram that his testosterone is high. He recently adopted a vegan diet. “It’s not as boring as I thought it would be,” he tells me. He closely monitors his biological age through InsideTracker, a company he advises that analyzes 43 biomarkers.

When I visited his office, he offered to show me his results. We looked at the graphs on a computer screen. First up: C-reactive protein, an indicator of inflammation. “I’m way below what a 20-year-old would have,” he says. He scrolled through more data, concluding, “I’m way off the chart for youth.”

Sinclair modified the Yamanaka formula, eliminating one transcription factor that has been implicated in cancer, and then used partial reprogramming in mice to regrow crushed optic nerves. “That was great,” he says, “but I thought if this is really age reversal, we should be able to reverse age-related disease.” So he tried it in mice with a glaucoma-like condition, and their vision returned. But they weren’t very old, so Sinclair decided to reprogram cells of geriatric mice experiencing age-related vision loss. A colleague who is an ophthalmology researcher bet him it wouldn’t work.

“And guess what?” Sinclair says. “It did.”

Since publishing the results in Nature in December 2020, Sinclair has continued the studies and says the benefits appear long-lasting. Meanwhile, he and the researchers in his lab are doing mind-bending back-to-the-future experiments in which they speed up aging in mice, turning them wizened and sluggish, or accelerate aging in just one organ or in all of them. By switching aging on, they hope to learn how to shut it off.

Sinclair targeted the optic nerve because it’s one of the first places affected by aging. Shortly after birth, we lose the ability to regenerate cells there. He believes his studies offer a game-changing model for treating spinal cord injuries and disorders of the central nervous system. If turning back cellular age can recapture lost vision, he says, why not also the ability to walk or remember?

Nobody knows when, or whether, a moon-shot technology like cellular reprogramming will do for humans what it accomplishes so marvelously in mice. But in the meantime, we can do plenty to take on aging. Researchers at the Harvard T.H. Chan School of Public Health looked at decades of data from 123,219 adults in the U.S. and found that five habits may increase life expectancy by 14 years in women and 12 years in men: good diet, regular exercise, healthy weight, not smoking, and not drinking too much.

“I think the one that gives you the most bang for your buck, if you’re only going to do one—which I don’t recommend—is exercise,” said Matt Kaeberlein, a professor of laboratory medicine and pathology and the director of the Healthy Aging and Longevity Research Institute at the University of Washington.

He’s a hard-core scientist, not a fitness guru. His lab developed a robotics platform called WormBot, which collects data simultaneously from hundreds of parallel experiments to tease out the factors that influence the life span of the roundworm C. elegans. He’s also testing rapamycin in dogs. But no matter how busy he gets, three days a week Kaeberlein, 51, heads to the makeshift gym in his garage and cycles through bench presses, squats, dead lifts, and shoulder lifts to maintain muscle mass. “For most people over 50, loss of muscle mass due to a sedentary lifestyle usually is one of the most important predictors of poor health outcomes later on,” he says.

Fitness experts argue endlessly about which exercise regimen best maximizes health and strength late in life. Similarly, nutrition experts disagree about the optimal diet—time-restricted eating, intermittent fasting, keto, vegan, Mediterranean, you name it.

Animal studies provide compelling evidence that severe calorie restriction increases life span. Whether that’s true for people has been notoriously difficult to determine. The National Institute on Aging initiated a large study two decades ago to measure the effects of a diet that cut calories by 25 percent. But even though participants received counseling, software to track what they ate, and meals for a while, they shaved calories by only 12 percent. I was reminded of the doctor who told me the best healthy diet is the one you’ll follow.

Becca Levy, a professor of epidemiology and psychology at Yale University, points to another important, controllable influence on healthy longevity: our beliefs about aging. In one study, which has been replicated around the world, Levy found that people in their 30s and 40s who had positive expectations for old age—they equated it with wisdom, for example, instead of decrepitude—were more likely to be in good health decades later. In another study, she showed that older people who have positive views of aging are much more likely to recover fully from a disabling injury. And in yet another, she found that positive views of old age were associated with a lower risk of Alzheimer’s. Levy has found that people with the brightest beliefs about aging live an average of seven and a half years longer than those with the gloomiest.

Reading research by scientists trying to unravel the mysteries of aging can make it hard to feel good about growing older. The idea of “curing” aging casts it as pathology. Published studies start, relentlessly, with bad news. “Aging is a degenerative process that leads to tissue dysfunction and death,” begins a typical paper. As I learned more about the science, I grew excited about the possibilities for breakthroughs but distressed about my own prospects as I approached 68.

Steve Horvath offered to run an epigenetic clock on me, a test with the anxiety-producing name of GrimAge. I sent him two vials of my blood. A while later I opened the report: My biological age was 3.3 years lower than my chronological age. The report offered a cheerful “congrats” and said, “You are already beating the clock!” But I felt let down. I certainly wasn’t in league with David Sinclair in bucking the tempest of time.

Then I thought about my mother, still enjoying life in her late 90s. Becca Levy’s research convinced me that my mom’s outlook at least partly explains her vitality. I’ve never heard her grumble about her birthday or say she can’t do something because she’s too old, a complaint I’m starting to hear from friends my age.

“No,” she says, when I point this out. “I’m not too old. I might do it slower, and I might do less of it. But I’m not too old to dance or walk or do anything I like to do.”

She pauses. “Well, I wouldn’t swim anymore.”

“Because you haven’t done it in a long time?”

“Because I don’t like the way I look in a bathing suit.”

Resources

nationalgeographic.com, “Can aging be cured? Scientists are giving it a try.” By Fran Smith;

Appendix Q–Walking is the Sixth Vital Sign

Mobility is key to staying healthy and independent as you age. We asked experts to weigh in on how to do it right—and when to start thinking about it.

Walking might seem simple. But it’s not, explains epidemiologist Peggy Cawthon, science director of the California Pacific Medical Center Research Institute. It’s an amazingly complex behavior that continues to baffle researchers, especially ones trying to understand how to improve our lives as we age.

“For reasons we don’t understand, the speed you walk is related to your risk of dying,” she says. Folks who can keep up the pace are likely to stick around longer.

And they’re likely to live better. Lack of mobility is one of the top reasons that seniors lose independence, according to the National Institute on Aging, and it’s also closely linked to cognitive decline.

Over the past decade, gait speed has emerged as the sixth vital sign, since it can predict a huge range of health problems. “Walking involves every system of the body,” adds Jessie VanSwearingen, professor of physical therapy at the University of Pittsburgh. Even if doctors haven’t noticed anything amiss, changes in someone’s walking could be a tipoff that a diagnosis isn’t far behind.

According to the National Institutes of Health, there are four types of exercises we should all be getting to help us stay active: endurance, strength, balance, and flexibility. That’s just the start of the equation. “I’m in the camp that exercise is important, but it’s not the elixir that solves all problems. No one thing will save you,” Cawthon says.

There’s also a lot left to learn about how the brain influences it all, notes On-Yee (Amy) Lo, of the Hebrew SeniorLife Marcus Institute for Aging Research and an Assistant Professor at Harvard Medical School and Beth Israel Deaconess Medical Center. She has seen plenty of patients with perfectly functioning muscles. “But when you tell them to move, they can’t,” she says.

So what, um, steps should we take to protect our mobility—especially as we get farther away from those toddler years? Here are a few ideas:

Don’t stop moving

Experts agree that pretty much the worst thing a person can do is to stop moving. You’ll feel the effects almost immediately, says Pete McCall, director of education for EōS Fitness and author of Smarter Recovery: A Practical Guide to Maximizing Training Results. Sitting for hours leaves him sore, and it’s the days when he uses his hands that his arthritis doesn’t bother him as much. These are helpful reminders that our bodies demand action.

“But I don’t need to crush myself at every workout,” says McCall, who shared his quick go-to routine for limbering up his spine, hips, and ankles on the American Council on Exercise website. “It’s almost like brushing my teeth. If I don’t do it for a day or two, I notice,” he says. He uses the moves—which include hip circles and getting down on one knee, and then reaching with the opposite arm to twist the upper body—before or after a workout, or as an active recovery day.

If that sounds too complicated, McCall’s suggestion is to follow the advice he gives his 80-year-old dad. “I yell at him to walk and do yoga,” he says, noting that poses such as cat-cow and the warrior series force you to pay attention to your spine.

Even if you’re injured, try to find something active that works for you, like swimming or biking. “The magic is whatever exercise people can do,” Lo says. In her case, as a working mom of a four-year-old, that’s usually chasing her kid around.

Curious about pickleball? Or taking up ballroom dancing? Don’t be afraid of learning new skills, says Jennifer Brach, professor of physical therapy at the University of Pittsburgh. “Find the program you enjoy, so you stick with it.”

Train yourself to walk with good technique

To truly improve your walking once it starts to decline, however, you need to think like an athlete. Imagine you want to play tennis, but you have a bad backhand. Playing lots of tennis won’t fix the problem, VanSwearingen says. You need to improve your technique. It’s the same thing with walking.

A treadmill can coach you on how it’s done. “It drags your foot behind you and makes you take a step,” she says. It also makes it easy to experiment with different speeds to find what is most comfortable. For most of the population, that is about 1.3 meters per second, or about three miles per hour, VanSwearingen says. To practice adaptability, she suggests occasionally bumping up your speed by 10 percent for a minute.

No matter what surface you’re strolling on, VanSwearingen offers this suggestion: “Walk from your feet.” Rather than thinking about picking up a foot and placing it in front of you, use your feet to provide propulsion and push the ground away. And don’t look down, unless you want to fall. “The brain assumes you want to go where you’re looking,” she adds.

This approach to walking is the basis of On the Move, a 12-week-long course developed at the University of Pittsburgh. Rather than focusing on strength and endurance—the typical targets for a fitness class—it emphasizes timing and coordination. “We use the analogy of cars. Instead of giving someone a bigger engine, our program is tuning up the system so it runs more efficiently,” Brach says. “When you’re more efficient, you can do more.”

For example, she explains, to initiate walking, you must subtly shift your weight back and to the side. “Many of our exercises start with a step back, so when you get that weight on the back foot, you can push off to step forward,” Brach says. Using these strategies to be become a better walker can lead to additional benefits like weight loss and lower blood pressure.

Give your brain a boost

Ultimately, the body part in charge of everything is your brain. So don’t forget that when crafting your mobility preservation plan. Cawthon points to the power of tai chi, which has been shown to improve balance and reduce the risk of falls. Scientists are investigating whether that’s because of the physical aspect of the practice or its cognitive demands, which include learning a specific sequence of movements.

A recent study published in the Annals of Internal Medicine touted the beneficial effects of “cognitively-enhanced” tai chi. Participants who did extra mental gymnastics—like spelling a word backward and forward as they moved through each pose—performed better on a mental cognition test than folks who did standard tai chi or stretching exercises.

Finding ways to protect against dementia is a big deal, says Lo, who notes that half of people with dementia experience falls, compared to 30 percent of the general older population. But a variety of promising interventions could help boost mobility, including non-invasive brain stimulation.

Many seniors know—but don’t follow—recommended physical activity guidelines, Lo explains. So she has been studying what happens when behavioral counseling is paired with a few zaps of electric current targeting an area of the brain related to motivation and executive function. Participants with the stimulation walked more steps on average than the control group, and they have been maintaining that even several months later, she says. Another study in the works will use brain stimulation to improve unsteady gait in older adults.

She’s also collaborating with music therapists to experiment with music stimulation. “Older adults with dementia or Parkinson’s disease may not be able to initiate movement, but if you play music, they are able to follow it,” Lo says.

Start planning now

So when should we face the music about our mobility? There is no definitive answer for when walking problems begin to crop up. “You should be as active as you can be at any age,” Cawthon says, noting that people who are healthy in their 20s and 30s are best equipped to handle future age-related challenges. “The best time to start is now. Next best is tomorrow,” she says.

One key moment to consider mobility is when you’re deciding where to live. Are you moving into a single-story place or multi-story building? Is there an elevator? “It’s hard to imagine when you’re buying a house that you might want to put in a ramp,” Cawthon says. But a home that is conducive to mobility can make a huge difference in how comfortably you’re able to maneuver through your environment.

What’s outside is just as critical. “If you live in a neighborhood with nice sidewalks that are well maintained and has a low crime rate, you’re more inclined to get out and walk,” Brach says. Areas where it’s easy to run errands on foot also encourage seniors to stay mobile.

VanSwearingen recommends paying attention to how you feel and what you’re thinking about. Say, you need to get up from your chair and cross the room. Hopefully, that’s an idea that barely registers. But if you find yourself concentrating on how you’re going to accomplish that task, it’s a warning sign. “If those thoughts are on your mind, it’s time,” she says.

Resources

nationalgeographic.com, “Walking is the sixth vital sign. Here’s how to do it right.” By Vicky Hallett;

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What’s responsible for the early timetable

Endocrine disrupting chemicals

Physical changes

A matter of perception

Sex and the aging voice

Treating voice disorders in aging adults

1. Mindset matters for aging well.

2. Outdoor adventure can change our mindset on aging.

3. Nature is medicinal.

4. Awe is critical for us on a biological level.

5. We actually can learn new things as we age—and learn better.

Phase Out Destructive Habits

How changes at the molecular level affect you

Limitations and unanswered questions

Can these bursts of aging be prevented?

The history of old age

When does old age begin?

Investigating superagers

Six key indicators of good health

Challenging the norms of who lifts heavy

Lifting heavy weights is for middle-aged women too

There’s always time to build back bone

Hallmarks of aging

A relentless loop

Aging better

Age-fighting behaviors

Genetic lessons from our 100-year-old elders

Lifestyle tips to live heathier, longer

What do longevity researchers do for themselves?

Get to know yourself better

Make friends and calm your mind

Facial aging clock

Applications of the technology

Future directions

Can aging be cured? Scientists are giving it a try

Don’t stop moving

Train yourself to walk with good technique

Give your brain a boost

Start planning now

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