Researchers Find Massive Biomolecular Changes Occur Between Ages 40 and 60

If you’ve ever felt like everything in your body is falling apart at once, it may not be a figment of your imagination. A new study from Stanford Medicine shows that the number of many molecules and microorganisms increases or decreases dramatically between the ages of 40 and 60.

The researchers analyzed thousands of different molecules in people aged 25 to 75, as well as their microbiomes (the bacteria, viruses, and fungi that live inside us and on our skin) and found that the abundance of most molecules and microbes does not change gradually or chronologically. Instead, we go through two periods of rapid change during our lives, on average around ages 44 and 60. A paper describing these findings is published in Aging of nature.

“We’re not just changing gradually over time; there are really dramatic changes,” said Michael Snyder, Ph.D., chair of the Department of Genetics and senior author of the study. “It turns out that the mid-40s are a period of dramatic change, as are the early 60s. And that’s true regardless of what class of molecules you’re studying.”

Xiaotao Shen, Ph.D., a former postdoctoral researcher in medicine at Stanford, is the study’s first author. Shen is now an assistant professor at Nanyang Technological University in Singapore.

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

Sudden changes in the number

Dr. Snyder, the Stanford W. Ascherman Professor of Genetics, and his colleagues were inspired to study the pace of molecular and microbial change by the observation that the risk of many age-related diseases does not increase gradually with age. For example, the risks of Alzheimer’s disease and cardiovascular disease increase sharply with age, but they increase gradually in people under age 60.

The researchers used data from 108 people they followed to better understand the biology of aging. The findings from the same group of volunteers in the study include the discovery of four distinct “ageotypes,” showing that the kidneys, liver, metabolism, and immune system age at different rates in different individuals.

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

They found that thousands of molecules and microbes experience changes in their abundance, either up or down. About 81 percent of all the molecules studied showed nonlinear fluctuations in number, meaning they changed more at some ages than others. When they looked for the groups of molecules with the greatest changes in quantity, they found that these transformations occurred most often at two times: when people were in their mid-40s and early 60s.

While much research has focused on how different molecules increase or decrease with age and how biological age may differ from chronological age, very little has looked at the pace of biological aging. Perhaps it’s not surprising that so many dramatic changes occur in the early 60s, Snyder said, because many risks for age-related diseases and other age-related phenomena are known to increase at this stage of life.

The researchers were somewhat surprised by the magnitude of the changes seen in their mid-40s. At first, they thought that menopause or perimenopause was causing big changes in the women in their study, skewing the overall group. But when they split the study group by gender, they found that the change was happening in men in their mid-40s as well.

“This suggests that while menopause or perimenopause may contribute to the changes seen in women in their mid-40s, there are likely other, more important factors that influence these changes in both men and women. Identifying and studying these factors should be a priority for future research,” Shen said.

Changes can influence health and disease risk

In people aged 40 to 60, significant changes were observed in the number of molecules related to alcohol, caffeine and lipid metabolism, cardiovascular diseases, skin and muscle. In people in their sixties, changes concerned carbohydrate and caffeine metabolism, immune regulation, kidney function, cardiovascular diseases, skin and muscle.

It’s possible that some of these changes are related to lifestyle or behavioral factors that are concentrated in these age groups, rather than biological factors, Snyder said. For example, impaired alcohol metabolism could result from increased drinking in the mid-40s, an often stressful time in life.

The team plans to explore the factors behind these clusters of changes. But whatever their causes, the existence of these clusters underscores the need for people to pay attention to their health, especially in their 40s and 60s, the researchers said. That could mean increasing physical activity to protect your heart and maintain muscle mass at those two ages, or cutting back on alcohol in your 40s as your ability to metabolize alcohol slows.

“I strongly believe that we should try to adapt our lifestyle while we are still healthy,” Snyder said.