Epigenetic Clocks of Biological Aging and Cognitively Healthy Longevity: The Women's Health Initiative Memory Study.

Andrea Z LaCroix and colleagues analyzed 5,844 women from the Women’s Health Initiative Memory Study. Fifteen epigenetic clocks were measured at baseline between 1996 and 1999. The investigators classified participants by survival to age 90 and cognitive status. A total of 1,726 women survived to 90 with preserved cognition, 956 survived to 90 with cognitive impairment, and 2,611 died before 90. Higher age acceleration on several clocks predicted lower odds of exceptional survival. The strongest associations were reported for AgeAccelGrim2, PCGrimAge, PCPhenoAge, and DunedinPACE. The clocks were associated with reaching 90, but none was associated with cognitive healthspan once survival status was considered. This is useful calibration for biomarker claims. An epigenetic clock can track mortality-related aging without identifying the biology needed for preserved cognition. The design is observational, and clock values were measured at one baseline visit. The study does not test whether changing a clock changes health or lifespan. It supports the use of epigenetic age as a risk marker, not as a validated treatment target.

All clocks were associated with exceptional longevity, but none were associated with cognitive healthspan. Future research should focus on developing clocks that differentiate long survival with and without preserved cognitive function.