We don’t age gradually as previously thought, but in ‘bursts,’ in our 40s and 60s, research shows

By Daryl Austin

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.”
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Credit: National Geographic