Happy Birthday! You are now another year older!

Actually, you may be a couple of years older than last year — or you may be a few years younger. The current view seems to be that aging is less connected to the calendar and more related to our choices, our genetics and our environment.

Online tests that claim to measure your true biological age — as opposed to your chronological age — are trendy right now, as are a wide variety of products, supplements and other strategies boasting that they can turn back our biological clocks. But are there steps you can take to slow the aging process? Actually, yes. Should you believe people selling interventions designed to reverse aging? Probably not.

A chemical clock or a crystal ball?

So, what is an aging clock, and how does it work?

“Biomarkers of aging can predict remaining health span and lifespan better than chronological age,” said Michael Greger, M.D., physician and author of the book How Not to Age. “There are broadly five types, including telomere length, composite blood tests, epigenetic clocks, transcriptional predictors based on changing gene expression and function tests that don’t involve taking blood or saliva.”

Greger pointed out that all these tests may provide interesting data, but there are limitations, and the results may vary widely.

“According to the American Federation for Aging Research, there is no sufficiently validated biological age test on the market,” Greger said. “The one with perhaps the best chance of eventually succeeding is the epigenetic clock.”

The epigenetic clock is designed to look at several different factors related to epigenetics, which is the study of how your behaviors and environment can cause changes that affect the way your genes work. Environmental factors and behaviors, such as smoking, diet and exercise, can result in epigenetic changes.

The best-known epigenetic clock is the Horvath Clock, created by biomathematician Steve Horvath, Ph.D., a researcher at the University of California, Los Angeles. His clock, first described in detail in the journal Nature in 2014, has provided researchers with a path to examine chemical and genetic changes.

“In the last decade or so, tools have been developed to allow us to look deeper at aging,” said Bruce Troen, M.D., director of the Landon Center on Aging and professor at the University of Kansas School of Medicine. “The Horvath Clock is perhaps the best known and the first to clearly show that we are products of our DNA. The way our DNA is modified changes with aging and with disease.”

Methylation, a chemical modification of DNA and other molecules that may be retained as cells divide to make more cells, is part of what epigenetic clocks are measuring.

“There are certain DNA sites on our chromosomes that so predictably methylate or demethylate as we age that it’s like clockwork, presenting a potential molecular crystal ball for human aging,” Greger said. “Out of the millions of methylation sites in our DNA, a tiny subset so dependably shifts over time that you can predict someone’s age within a few years just by strategically measuring the methylation pattern in a few hundred — or even just a few dozen — sites in someone’s three-billion-letter genome.”

Why should we watch the clock?

What is the point of knowing your biological age versus your chronological age? If you can measure your biological age, you may begin to understand how to change it.

According to the Census Bureau, by 2030 the United States will have more people over age 65 than those under 18. Also, the number of Americans ages 65 and older is projected to increase from 58 million in 2022 to 82 million by 2050 (a 47% increase), and the 65-and-older age group’s share of the total population is projected to rise from 17% to 23%, according to recent data from the Population Reference Bureau.

“What we’re seeing now is the initial wave of the silver tsunami,” said Ken Seldeen, Ph.D., associate professor of geriatric medicine at the KU School of Medicine. “The eventual impact on our health care systems is going to be dramatic.”

It is also clear that if we can slow aging, we can slow many diseases associated with aging, from stroke and heart disease to Alzheimer’s disease.

“The biggest risk factor for Alzheimer’s disease is aging,” said Russell Swerdlow, M.D., professor of medicine and co-director of the KU Alzheimer’s Disease Research Center. “Scientists have so many questions, and it is often hard to study aging variables in humans.”

Swerdlow said that is why it is so important to study cellular changes, even if those studies cannot be easily extrapolated to humans.

“In models, you can manipulate things to see how one change affects another. We know some of the hallmarks of aging are mitochondrial dysfunction and telomere shortening,” Swerdlow said. “But are the mitochondria driving aging or is aging driving changes in mitochondria?”

Studying aging, from cells to communities

While Swerdlow is more focused on mitochondria in the cell, Seldeen and Lee Chaves, Ph.D., assistant professor of geriatric medicine at KU School of Medicine, are working in the laboratory to understand more broadly how different factors impact aging processes. Both Seldeen and Chaves came to the University of Kansas from the University of Buffalo with Troen to study aging and geroscience.,

”Our goal is to understand the basic mechanisms of aging, from cells to animal models, and then to translate that into people and into communities,” Seldeen said.

Chaves pointed out that, in addition to looking at aging across the board, he and his colleagues are examining both substances and processes. He said one of their targets is how chronic inflammation affects aging.

“Inflammation is the body’s necessary response to an injury, but chronic inflammation seems to be linked to premature aging and the acceleration of disease,” Chaves said. “If it does, what can we do to prevent or reduce chronic inflammation?”

Troen, Chaves and Seldeen are working with both the Landon Center on Aging and with the Veteran’s Administration to examine what type of aging interventions might have an impact on humans. There are many functional tests used to determine health among older people, from gait speed to resilience to grip strength. Can interventions improve performance on these tests? Can exercise improve results? Those are all relevant questions for these researchers.

“What can we do to enhance healthy aging?” Troen asked. “How can we enhance health span — our ability to retain our physical and cognitive abilities — and not just lifespan? It’s the life in your years, not just the years in your life that matters.”

Telomeres and aging

Another area that researchers think might be a key to reversing aging are telomeres. Telomeres are structures made from DNA sequences and proteins found at the ends of chromosomes. They cap and protect the end of a chromosome like the end of a shoelace.

Merlin Butler, M.D. professor emeritus of psychiatry, behavioral sciences and pediatrics and director of the Division of Research and Genetics at KU School of Medicine, has studied telomeres over the years for his work in genetics and rare disease. Butler said it is already known that telomeres are needed for cell division and telomere length shortens with age. The rate of telomere shortening may be related to the pace of aging.

Over the years, Butler has studied and published articles about telomeres, including their potential role in cancer. Studies have shown that people with longer telomeres live longer lives and people with shorter telomeres live shorter lives. As telomeres shorten, so does life expectancy — sometimes for reasons that are not obvious. But those with shorter telomeres have more strokes, more cancer and more cardiovascular disease.

“It is interesting that we lose about one telomere per week or 50 per year,” said Butler. “And when the telomeres become shortened and unstable, then telomeric associations occur, leading to terminal damage and cell division and death.”

Longevity and aging differences

There is little doubt that Americans are heading in the wrong direction when it comes to longevity. According to an article in Harvard Health, life expectancy in the United States was on the rise until 2020.

“With rare exceptions, life expectancy has been on the rise in the United States,” wrote Robert H. Shmerling, M.D. “It was 47 years in 1900, 68 years in 1950, and by 2019 it had risen to nearly 79 years. But it fell to 77 in 2020 and dropped further, to just over 76, in 2021. That's the largest decrease over a two-year span since the 1920s,” he said, noting that COVID-19 and drug overdoses seemed to be the biggest contributors to the decline.

When it comes to longevity, there are immense disparities in underserved populations, with differences evident by race, socioeconomic status and even gender. Statistically, women live longer than men, but that may not be the only difference in how we age.

“Women may age differently than men,” said Amber Watts, Ph.D., associate professor in clinical psychology in the Department of Psychology at the University of Kansas. “Estrogen may be a part of it, and men’s Y chromosome also may be associated with more health problems.”

Watts also studies how menopause relates to aging and how estrogen, and the lack of estrogen, may impact aging.

“We have to think about what estrogen does over the lifespan,” she said. “Estrogen is very important for the heart and for the brain.”

Part of women aging better over time may include physicians prescribing menopausal hormone therapy to those women who would benefit from it.

“It’s not appropriate for some, but in general it’s well tolerated and helpful for many women,” Watts said.

Watts notes that a flawed study from several years ago is still influencing some physicians who refuse to consider hormone therapy. She is working to make sure that women and health care professionals have a better understanding of the impact of menopause on women’s health, including on their aging process.

“Health care providers are not well-educated about menopause, and they need to be,” she said, noting that too many doctors are quick to dismiss women’s menopausal or perimenopausal symptoms. “When a woman comes in to see her doctor and she says she cannot sleep, they prescribe a sleeping pill when what she actually needs is hormone supplementation.”

Watts noted that estrogen isn’t a magic pill that can stop aging either.

“There is no miracle solution,” Watts said. “But there are lifestyle interventions that modify these processes of aging.”

Can we slow the ticking of the clock?

If there are so many drivers of aging, what can we do to slow the ticking of our clock? Can we improve our biological age? Researchers agree that there is much still to learn, but it is clear there are known ways to decelerate aging.

“One of the best ways to help yourself is to ‘do no harm,’” said Swerdlow, noting we do have a sense of what choices are the wrong ones.

Studies have found that lifestyle choices, from smoking to obesity, stress, lack of physical activity and even exposure to pollution, can shorten lifespan. Many of those same factors seem to impede mitochondria and are proven to increase risk factors for a variety of diseases.

Greger points out that oxidation seems ripe for intervention as well.

“Lowering antioxidant defenses in mice results in accelerated hearing loss, cataract formation and cardiac dysfunction, whereas increasing antioxidant capacity affects the reverse, delaying age-related disease,” he said.

While there isn’t yet a pill, supplement or drug that is proven to reverse aging in humans, numerous studies point to lifestyle interventions that can make a difference, with exercise and plant-based eating as heavy hitters.

The National Council on Aging points to exercise as the most successful intervention found thus far, as Linda P. Fried, M.D., MPH, dean of Columbia’s Mailman School of Public Health and an internationally recognized gerontologist explained.

“Exercise is the closest thing we’ve found to a magic pill for combating the effects of aging. That’s because it works on every physiological system and keeps your entire body fine-tuned. It even stimulates your brain and helps to prevent cognitive decline.”

Greger, who devotes much of his book, How Not to Age, to an examination of studies that show how whole-food, plant-based diets can improve health and slow aging, also has a nonprofit, Nutritionfacts.org, that provides free information on peer-reviewed studies about nutrition. Greger points out that plants have developed a variety of natural defenses for predators, and those defenses may benefit humans as we seek to enhance our health span. But Greger said it is up to us to choose fruits and vegetables for ourselves, because they don’t have a pharmaceutical company touting them.

“We don’t see ads on TV for broccoli for the same reason that groundbreaking research on the power of foods and eating patterns to affect our health and longevity gets lost and buried in the medical literature,” he said. “Put very simply: There is a lack of a profit-driven motive. Healthful eating and nutrition research may not make anyone money, but what if our lives would profit?”

So perhaps we should ignore calendars that determine our chronological age. Instead, we should consult our digital daily planners, where we have our exercise schedule and our grocery list, full of plants and healthy whole foods. The choices reflected in that planner are truly the factors that might be able to turn back the clock.