A Stanford University School of Medicine study found that between your mid-40s and early 60s, there are major changes in the molecular and microbial levels in your body that could affect your health and risk of diseases related to aging.
If you’ve ever felt like everything in your body was falling apart at once, you might not be imagining it: Many of the molecules and microbes in our bodies increase or decrease in number dramatically between our 40s and 60s, according to a new study from the Stanford University School of Medicine.
By assessing thousands of molecules and their microbiomes (the bacteria, viruses, and fungi that live in our bodies and on our skin) in people between the ages of 25 and 75, the researchers found that the abundance of most molecules and microbes doesn’t change gradually over time. Rather, we experience two periods of rapid change over our lifetimes, on average around age 44 and 60. A paper describing these findings was recently published in Nature Aging.
“We’re not changing gradually over time, we’re changing really dramatically,” said Michael Snyder, PhD, chair of the Genetics Department and senior author of the study. “It turns out that your mid-40s are a time of dramatic change, as are your early 60s, and that’s true no matter what class of molecule you’re looking at.”
Dr. Xiaotao Shen, a former postdoctoral fellow at the Stanford University School of Medicine and now an assistant professor at Nanyang Technological University in Singapore, is the first author of the study.
These big changes are likely to have an impact on our health. Cardiovascular disease Significant changes were seen at both time points, with those related to immune function changing in people in their early 60s.
Sudden changes in numbers
Snyder, the W. Asherman, MD, FACS Professor of Genetics at Stanford University, and his colleagues were inspired to examine rates of molecular and microbial change by the observation that the risk of developing many age-related diseases does not increase stepwise with age. For example, Alzheimer’s disease While the risk increases slowly before age 60, the risk of cardiovascular disease and diabetes increases sharply as people get older.
The researchers used data from 108 people they followed to better understand the biological aspects of ageing. Previous findings from this same group of study volunteers included the discovery of four different “ageotypes,” showing that people age at different rates in their kidneys, liver, metabolism and immune systems.
The new study analyzed participants who donated blood and other biological samples every few months over several years, and scientists tracked the different types of molecules that were present in these samples. RNAand looked at changes in proteins, metabolites, and the participants’ microbiomes. The researchers tracked age-related changes in more than 135,000 molecules and microbes, collecting a total of about 250 billion different data points.
The researchers found that thousands of molecules and microbes changed in abundance, either increasing or decreasing. About 81% of the molecules studied showed nonlinear variations in abundance, meaning they changed more at certain ages than at others. By looking for populations of molecules with the largest changes in abundance, they found that these changes occurred most frequently at two times: in the mid-40s and early 60s.
While many studies have focused on how different molecules increase or decrease with age and how biological age differs from chronological age, few have looked at the rate of biological aging. That so many dramatic changes occur in the early 60s is perhaps not surprising, Snyder says, because many age-related disease risks and other age-related phenomena are known to increase at that point in life.
The big changes that occurred in the mid-40s came as a bit of a surprise to the scientists. They initially assumed that the big changes in the women in their study were due to menopause or the perimenopause period, which accounted for the skewness across the group. But when they separated the study group by gender, they found that changes were also occurring in men in their mid-40s.
“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 influencing these changes in both men and women. Identifying and studying these factors should be a priority for future research,” Shen said.
Changes can affect health and disease risk
Those in their 40s showed significant changes in a number of molecules related to alcohol, caffeine, lipid metabolism, cardiovascular disease, and skin and muscle. Those in their 60s showed changes related to carbohydrate and caffeine metabolism, immune regulation, kidney function, cardiovascular disease, and skin and muscle.
Snyder said some of these changes may not be due to biological factors, but rather to lifestyle and behavioral factors that are more concentrated in these age groups. For example, dysfunction in alcohol metabolism could be due to increased alcohol consumption in people in their mid-40s, which is often a stressful time in life.
The team plans to investigate what contributes to these clusters of changes. But whatever the cause, the presence of these clusters indicates that people need to pay more attention to their health, especially those in their 40s and 60s. That might mean increasing exercise at both ages to protect the heart and maintain muscle mass, and reducing alcohol intake in people in their 40s, when their ability to metabolize alcohol declines.
“I’m a big believer in trying to make lifestyle adjustments while you’re healthy,” Snyder said.
Reference: Xiaotao Shen, Chuchu Wang, Xin Zhou, Wenyu Zhou, Daniel Hornburg, Si Wu and Michael P. Snyder, “Nonlinear dynamics of multi-omics profiles in human aging,” 14 August 2024, Nature Aging.
DOI: 10.1038/s43587-024-00692-2
This study National Institutes of Health (Grants U54DK102556, R01 DK110186-03, R01HG008164, NIH S10OD020141, UL1 TR001085, P30DK116074) and the Stanford Data Science Initiative.
