Stanford Medicine study reveals we experience two massive biomolecular shifts as we age – one in our 40s and one in our 60s.
Significant change can be stressful – divorce, death and moving all make the list – but when it comes to aging, a new paper identifies two flashpoints of enormous biological change. The recent study, by researchers at Stanford Medicine, uncovered evidence that human aging does not occur at a constant, gradual pace – but rather is marked by two significant bursts of molecular change. These bursts, observed in people around the ages of 44 and 60, suggest that aging may be driven by more complex biological processes than previously thought. The findings, published in Nature Aging, are based on comprehensive multi-omics profiling of 108 participants, providing a detailed look at how the human body changes during these key periods of life [1].
Longevity.Technology: The research sheds light on the nonlinear nature of aging, challenging the traditional view that aging is a steady, continuous process. By understanding why and how these bursts of aging occur, scientists may be able to uncover more about the mechanisms of aging and leverage that knowledge to improve both lifespan and healthspan. The findings also highlight the ever-evolving nature of aging research, which continues to refine our understanding of how and why we age.
The Stanford Medicine team, led by Professor Michael Snyder, PhD, analyzed a vast array of molecular data from participants aged between 25 and 75 years. Over a period spanning several years, the researchers collected blood and other biological samples from the participants, tracking more than 135,000 different molecules and microorganisms. The data set included a total of nearly 250 billion distinct data points, making this one of the most comprehensive studies of its kind [1].
Snyder and his colleagues found that the abundance of molecules and microbes in the human body does not shift gradually over time. Instead, these changes occur in two distinct bursts: one in the mid-40s and another in the early 60s. “We’re not just changing gradually over time; there are some really dramatic changes,” Snyder explained. “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 [2].”
The study’s findings suggest that these bursts of aging are not limited to specific types of molecules; rather, they occur across a wide range of biological markers, including RNA, proteins and metabolites, as well as components of the microbiome, the bacteria, viruses and fungi that live in and on our bodies. This broad range of affected molecules highlights the complexity of the aging process and suggests that these bursts of aging are likely driven by a coordinated, systemic alteration across multiple molecular components.
One of the most striking aspects of the study is the identification of specific molecules and functional pathways associated with the two bursts of aging. In the mid-40s, significant changes were observed in molecules related to alcohol, caffeine and lipid metabolism, as well as those associated with cardiovascular disease and skin and muscle function. By the early 60s, changes were more pronounced in molecules linked to carbohydrate metabolism, immune regulation, kidney function and continued shifts in cardiovascular disease risk [1].
Interestingly, the researchers initially suspected that the burst of changes in the mid-40s might be related to menopause or perimenopause in women. However, further analysis revealed that men experienced similar shifts in molecular abundance during this period [1].
“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,” said Xiaotao Shen, PhD, the study’s first author, who added that future research should make identifying and studying these factors a priority [2].
The implications of these findings extend beyond a better understanding of the aging process itself. The researchers believe that these bursts of molecular change could have a significant impact on health and disease risk. For example, the study identified a sharp rise in the abundance of molecules related to cardiovascular disease around both the 44-year and 60-year marks. Similarly, immune function and carbohydrate metabolism were found to change significantly in people in their early 60s.
These findings suggest that the risk of developing age-related diseases may not increase incrementally with age, but instead, may rise sharply during these periods of rapid molecular change [1]. Snyder makes the point that some of these changes could be tied to lifestyle or behavioral factors that cluster at these age groups, rather than being driven purely by biological factors. For instance, the study found that dysfunction in alcohol metabolism could be linked to increased alcohol consumption in people’s mid-40s, often a stressful period of life.
The Stanford team plans to continue investigating the drivers of these molecular changes, with the hope of identifying potential interventions that could help mitigate the impact of these aging bursts. But it is clear that paying attention to one’s health during these critical periods is important, and the researchers suggest that increasing exercise and reducing alcohol consumption could help counteract some of the molecular changes observed in the study. “I’m a big believer that we should try to adjust our lifestyles while we’re still healthy,” said Snyder [2].
The research also raises important questions about the relationship between these bursts of molecular change and other aspects of aging, such as functional decline, disease occurrence and mortality risk. The study’s authors argue that further research is needed to explore these connections, particularly through long-term cohort studies that track molecular markers alongside medical records, functional assessments and mortality data.
[1] https://www.nature.com/articles/s43587-024-00692-2
