A team working with data from the MULTI Consortium has built 38 sex-specific biological aging clocks covering 15 organ systems, and reports that separating female and male aging trajectories changes what those clocks say about disease risk. The work, published in Nature Medicine, drew on genetics, proteomics, metabolomics, MRI scans, longitudinal clinical records, and data from a clinical trial. The resulting clocks predicted disease onset, all-cause mortality, and progression from mild cognitive impairment to Alzheimer's disease.
The premise is that chronological age is a blunt instrument. Two people born the same year can differ in biological age, and that difference is not uniform across the body - a person's kidneys, brain, or immune system may be aging at different rates. Males and females share broadly the same organ and tissue architecture, yet their susceptibility to particular diseases later in life diverges. Most existing biological clocks were trained on sex-pooled samples, which effectively averages away those differences.
For dementia research, the Alzheimer's-relevant result is twofold. The clocks tracked who moved from mild cognitive impairment to a diagnosis of Alzheimer's, and they were associated with sex-dependent cognitive trajectories in the A4 solanezumab trial - meaning the same biological aging signal appeared to relate to cognitive change differently in women and men within a trial population.
If sex-specific clocks stratify risk better than pooled ones, the practical payoff would be in selecting and monitoring participants in prevention trials, where identifying who is likely to decline is a persistent problem. The study establishes associations across multiple data types rather than demonstrating that these clocks work as clinical tools, and how they perform in routine care remains to be tested.