Clinical aging clocks uncover different metabolic turning points for men and women

A new study published in Nature Aging on August 25th reveals distinct metabolic turning points for aging, with different trajectories for men and women. Researchers analyzed routine clinical data from 104,208 adults aged 18–98 across three centers in China. Using 172 common indicators, they created sex-specific aging clocks to estimate physiological aging from routine health examinations.

The findings show that men experience a prominent metabolic transition between the ages of 35–45, marked by changes in body mass index, triglycerides, and cholesterol levels. In contrast, women undergo a later transition around menopause, between the ages of 55–65, characterized by significant endocrine changes and deteriorating lipid profiles.

Despite these divergent aging patterns, the study found that overall physiological differences between men and women tend to diminish later in life. Additionally, several metabolic factors and tumor-related markers accumulate with age and are associated with accelerated aging. Experimental evidence suggests that factors like elevated glucose, lipids, uric acid, CEA, and HE4 can induce aging-related changes in vascular endothelial cells, indicating that these circulating molecules may actively contribute to the aging process rather than merely reflecting it.

However, the research also highlights potential strategies for mitigating age-associated metabolic burdens. For instance, metformin helped reverse high-glucose-induced endothelial aging, and switching mice from a high-fat diet to a normal diet improved several liver aging-related features. The study emphasizes the importance of sex-specific assessment and intervention throughout the lifespan, suggesting that reducing the age-related metabolic burden could promote healthy aging.