Midlife and early senior years marked by dramatic molecular shifts

If you’ve ever felt like everything in your body is breaking down at once, it might not be your imagination. A new study from Stanford Medicine shows that many of our molecules and microorganisms increase or decrease dramatically in number during the 1940s and 1960s.

Researchers have assessed many thousands of different molecules in people aged 25 to 75, as well as their microbiomes; the bacteria, viruses and fungi that live in us and on our skin -; and found that the abundance of most molecules and microbes does not change in a gradual, chronological manner. Instead, we experience two periods of rapid change during our lifetime, on average around ages 44 and 60. An article describing these findings will be published in the journal. Nature aging August 14.

We don’t just change gradually over time; there are some really dramatic changes. It turns out that the mid-1940s is a time of dramatic change, just like the early 1960s. And that’s true no matter what class of molecules you look at.”

Michael Snyder, PhD, chair of genetics and senior author of the study

Xiaotao Shen, PhD, a former Stanford Medicine postdoctoral scholar, was the study’s first author. Shen is now an assistant professor at Nanyang Technological University Singapore.

These major changes are likely to impact our health; the number of molecules associated with cardiovascular disease showed significant changes at both time points, and the number of molecules associated with immune function changed in people in their early 60s.

Abrupt changes in numbers

Snyder, Stanford W. Ascherman, MD, FACS professor of genetics, and his colleagues were inspired to look at the rate of molecular and microbial shifts by the observation that the risk of developing many age-related diseases does not increase incrementally with age. . For example, the risk of Alzheimer’s disease and cardiovascular disease increases sharply with older age, compared to a gradual increase in risk for people under 60.

The researchers used data from 108 people they followed to better understand the biology of aging. Past insights from the same group of research volunteers include the discovery of four different ‘ageotypes’, showing that people’s kidneys, livers, metabolism and immune system age at different rates in different people.

The new study analyzed participants who donated blood and other biological samples every few months for several years; the scientists monitored many different types of molecules in these samples, including RNA, proteins and metabolites, as well as shifts in the participants’ microbiomes. The researchers monitored age-related changes in more than 135,000 different molecules and microbes, for a total of almost 250 billion different data points.

They found that thousands of molecules and microbes undergo shifts in their abundance, both increasing and decreasing; About 81% of all the molecules they studied showed non-linear fluctuations in number, meaning they changed more at certain ages than at other times. When they looked for clusters of molecules with the largest changes in quantity, they found that these transformations occurred most frequently in two time periods: when people were in their mid-40s and when they were in their early 60s.

While much research has focused on how different molecules increase or decrease as we age and how biological age may differ from chronological age, few have looked at the rate of biological aging. That so many dramatic changes occur in the early 1960s may not be surprising, Snyder said, because many age-related disease risks and other age-related phenomena are known to increase at that time in life.

The large number of changes in the mid-1940s was somewhat surprising to scientists. Initially, they assumed that menopause or perimenopause caused major changes in the women in their study, creating a skewed picture for the entire group. But when they split the study group by gender, they found that the shift also happened among men in their mid-40s.

“This suggests that while menopause or perimenopause may contribute to the changes seen in women in their mid-forties, there are likely other, more important factors influencing these changes in both men and women. Identifying and studying these factors should be a priority for the future. research,” Shen said.

Changes can affect health and disease risk

In their forties, significant changes were observed in the number of molecules associated with the metabolism of alcohol, caffeine and lipids; cardiovascular disease; and skin and muscles. In people over 60, the changes were related to carbohydrate and caffeine metabolism, immune regulation, kidney function, cardiovascular disease and skin and muscle.

It’s possible that some of these changes are related to lifestyle or behavioral factors that occur in these age groups, rather than being caused by biological factors, Snyder said. For example, alcohol metabolism dysfunction could result from an increase in alcohol consumption in the mid-40s, often a stressful time in life.

The team plans to investigate the driving forces behind these clusters of change. But whatever the causes, the existence of these clusters indicates that people need to pay attention to their health, especially in their 40s and 60s, the researchers said. That could look like increasing exercise to protect your heart and maintain muscle mass at both ages, or reducing alcohol consumption in your 40s because your ability to metabolize alcohol slows.

“I’m a big believer that we should try to make lifestyle changes while we’re still healthy,” Snyder said.

The study was funded by the National Institutes of Health (grants U54DK102556, R01 DK110186-03, R01HG008164, NIH S10OD020141, UL1 TR001085, and P30DK116074) and the Stanford Data Science Initiative.