Sex‑Specific Organ Aging Clocks Show Divergent Alzheimer’s Risk
A team at Columbia University, which has been building organ‑specific biological age models since 2023, retrained all 38 of those clocks separately for men and women on September 16 instead of using a mixed sample. The sex‑specific models proved more accurate than the combined versions and showed less over‑fitting.
A genome‑wide scan of the 38 models linked them to 359 DNA loci, many of which were active in only one sex; liver and metabolism pathways were more heritable in women, while immunity and skin showed stronger genetic effects in men. Brain‑age clocks also relied on different blood proteins — SLITRK1 for women and a set of eight other proteins for men.
In the ADNI cohort of people at risk for Alzheimer’s, each standard‑deviation increase in brain‑age raised the odds of moving from mild cognitive impairment to disease by 74% for men and 125% for women. The same pattern appeared in data from the solanezumab antibody trial: accelerated brain‑age predicted memory loss over 240 weeks in both sexes, whereas slower brain‑age helped women retain cognition better than men.
When predicting mortality, the female‑specific model tied risk to a
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