Biological Aging Clocks Show Differences by Sex

Key Developments:

• Researchers developed 38 aging clocks across 15 organ systems
• Female and male aging patterns differed across several organs
• Brain aging clock linked to Alzheimer’s progression
• Researchers caution that broader validation is still needed

(News Medical Life Sciences) — September 18, 2026: Researchers have developed 38 sex-specific biological aging clocks across 15 organ systems, finding that biological aging patterns can differ between females and males across organs, genetic factors and disease-related outcomes.

The study, published in Nature Medicine on September 16, used data from genetics, proteomics, metabolomics, magnetic resonance imaging (MRI), clinical records and a clinical trial to examine how biological aging varies between the sexes.

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Biological aging refers to changes in the body's physiological systems that may not correspond exactly with a person's chronological age. The researchers used biological aging clocks to estimate these differences and examined whether separate models for females and males could provide more appropriate reference points.

The research team, led by the MULTI Consortium, developed sex-specific models using data covering 15 organ systems and three molecular data layers. The researchers compared these models with sex-pooled approaches, which combine female and male data.

The analysis found differences in the genetic contribution to biological aging across several organs. For example, some liver and metabolic aging measures showed higher estimated heritability in females, while certain immune, spleen and skin measures showed higher estimates in males.

The researchers also identified differences in the relationship between biological aging measures and disease-related outcomes. Metabolic aging measures showed stronger associations with some Alzheimer’s disease, sleep and psychiatric traits in females, while some metabolic and diabetes-related signals were stronger in males. The study also reported sex-dependent associations involving cardiometabolic conditions.

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Brain aging and Alzheimer’s disease

One of the study's findings involved brain aging and Alzheimer’s disease. Researchers used MRI-based brain biological age measures alongside longitudinal data from the Alzheimer's Disease Neuroimaging Initiative.

The brain aging clock was associated with progression from mild cognitive impairment (MCI) to Alzheimer’s disease in both females and males, with a stronger statistical association observed in females.

Among the participants studied, a one-standard-deviation increase in the brain age measure was associated with a hazard ratio of 1.74 in males and 2.25 in females for progression from MCI to Alzheimer’s disease. These figures describe associations within the study and do not establish that accelerated biological aging directly causes Alzheimer’s disease.

The researchers also examined participants from the A4 clinical trial of solanezumab. Among participants who received the treatment, females with slower brain-aging trajectories had higher cognitive composite scores at week 240 than males. The study did not observe the same sex difference among participants with faster brain-aging trajectories.

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The clocks also showed associations with future disease onset and all-cause mortality. In females, 12 biological-age-gap and mortality pairs reached the study's statistical threshold, while 14 such pairs did so in males. The researchers reported that these associations varied by organ and biological system.

Image Credit: Lightspring / Shutterstock.

Researchers highlight study limitations

The authors caution that the findings do not mean that one biological aging model should replace all others.

The study notes that some disease-related genetic datasets were based on sex-pooled information. The UK Biobank also had limited repeat MRI and omics measurements, while the genetic analyses were restricted to people of European ancestry. The models did not explicitly account for factors such as hormonal status, pregnancy history, or social and gender-related exposures.

The researchers also reported that age-prediction performance was modest and said that external validation at a larger biobank scale remains necessary.

Rather than arguing that sex-specific models should replace sex-pooled approaches, the researchers said both approaches have a role. Sex-specific models may help establish appropriate normative references and identify differences that pooled models can obscure, while sex-pooled and sex-interaction analyses can continue to examine biological similarities and differences between females and males.

Sex-specific biological aging clocks predict DEs, mortality, AD progression and cognitive decline in the solanezumab trial. CREDIT: Nature Medicine.

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The study was published as an open-access article in Nature Medicine on September 16, 2026, with the version of record dated the same day. The research was received by the journal on April 4 and accepted on August 18.

The findings add to research into biological aging by examining aging trajectories at the level of individual organs and molecular systems rather than relying solely on chronological age or a single whole-body measure. Further studies involving more diverse populations and repeated measurements will be needed to determine how consistently these sex-specific patterns apply.

Journal reference:

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

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