Sex-Specific Biological Clocks Reveal How Aging Differs Across Women and Men: Study

Biological ageing may differ substantially between men and women and across organs, according to a study published in Nature Medicine.

Researchers developed 38 sex-specific biological ageing clocks covering 15 organ systems using genetic, proteomic, metabolomic, MRI and clinical data. They also analysed longitudinal data and outcomes from the A4 clinical trial of solanezumab.

Unlike chronological age, biological age reflects physiological changes that can vary between individuals and organs. The researchers found that several biological ageing measures showed different genetic patterns and disease associations in males and females.

Some metabolic ageing signals related to Alzheimer’s disease, sleep disorders and psychiatric traits were stronger in females. Hepatic and digestive metabolic ageing measures were also associated with cardiometabolic outcomes in females. In males, immune and endocrine ageing measures showed stronger associations with metabolic syndrome, lipid abnormalities, hypertension, diabetes-related changes and coronary interventions.

The ageing clocks also showed associations with future disease. In females, higher heart MRI-derived biological age was linked with hypertension, while higher immune and digestive metabolic age measures were associated with cardiometabolic conditions including hypercholesterolaemia and type 2 diabetes. Similar associations were identified in males involving endocrine and metabolic ageing measures.

Brain biological age was particularly associated with Alzheimer’s disease progression. Among people with mild cognitive impairment, each standard-deviation increase in brain age was associated with a 74% higher hazard of progression to Alzheimer’s disease in men and a 125% higher hazard in women. The clocks did not significantly predict progression from normal cognition to mild cognitive impairment.

The researchers also identified sex-specific protein signatures associated with brain and spleen ageing.

However, the study has important limitations. Much of the genetic data involved European-ancestry participants, several disease datasets were sex-pooled, and the models did not account for hormonal status, pregnancy history or social factors. External validation is also needed.

The findings suggest that sex-specific biological ageing measures could potentially improve future disease-risk assessment.

REFERENCE: The MULTI Consortium., Song, Z., Feng, D. et al. (2026). Sex-specific biological aging clocks across organs and omics. Nature Medicine, DOI: 10.1038/s41591-026-04662-6, https://www.nature.com/articles/s41591-026-04662-6