If you’ve ever felt like your body is breaking down all at the same time, it might not just be in your head. A new study from Stanford Medicine reveals that many of our body’s molecules and microorganisms experience significant shifts in number during our 40s and 60s.

The research examined thousands of molecules and the microbiomes — the bacteria, viruses, and fungi within and on our bodies — in individuals aged 25 to 75. The findings showed that the abundance of most molecules and microbes doesn’t gradually shift with age. Instead, there are two periods of rapid change, around ages 44 and 60. These results are detailed in a paper to be published in Nature Aging on August 14.

“We’re not just changing gradually over time; there are some really dramatic changes,” said Michael Snyder, PhD, chair of genetics and the study’s senior author. “It turns out the mid-40s is a time of dramatic change, as is the early 60s. And that’s true no matter what class of molecules you look at.”

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

These significant changes likely affect our health — for instance, molecules associated with cardiovascular disease changed notably at both age points, and those linked to immune function altered in people in their early 60s.

Rapid, Molecular Changes

Snyder and his team, inspired by the observation that age-related disease risks don’t rise steadily but often spike later in life, investigated the pace of molecular and microbial changes. For instance, the risk for Alzheimer’s and cardiovascular diseases increases sharply in older age, compared to the gradual increase seen in those under 60.

Using data from 108 individuals tracked to understand aging better, the researchers analyzed samples, including blood and other biological materials, collected every few months over several years. They monitored various molecules, such as RNA, proteins, and metabolites, and observed changes in the microbiomes. In total, they tracked more than 135,000 different molecules and microbes, accumulating nearly 250 billion data points.

The study found that around 81% of the molecules examined showed non-linear fluctuations in number, meaning they changed more significantly at certain ages. These shifts were most prominent during two periods: the mid-40s and early 60s.

Although much research has focused on how individual molecules change with age, few have examined the rate of biological aging. According to Snyder, the dramatic changes in the early 60s align with the well-known increase in age-related disease risks and other age-related phenomena during this time.

However, the cluster of changes in the mid-40s surprised the scientists. Initially, they thought that menopause or perimenopause in women might be the cause, skewing the data. But when they separated the data by sex, they found that men also experienced significant changes in their mid-40s.

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

Health and Disease Risk Impacts

In people in their 40s, researchers observed significant changes in molecules related to alcohol, caffeine, and lipid metabolism; cardiovascular disease; and skin and muscle. In those in their 60s, changes were seen in carbohydrate and caffeine metabolism, immune regulation, kidney function, cardiovascular disease, and skin and muscle.

Some of these changes could be linked to lifestyle or behavioral factors common at these ages rather than purely biological causes, Snyder suggested. For example, an increase in alcohol consumption during the often-stressful mid-40s might lead to dysfunction in alcohol metabolism.

The researchers plan to investigate the causes behind these clusters of change further. Regardless of their origins, these findings emphasize the importance of paying attention to health in your 40s and 60s. This could mean increasing exercise to maintain heart health and muscle mass or reducing alcohol consumption in your 40s as your ability to metabolize alcohol declines.

“I’m a big believer that we should try to adjust our lifestyles while we’re still healthy,” Snyder said.

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