Epigenetic Clocks Relate to Four Age-Related Health Outcomes Similarly across Three Countries

Abstract

Background Measures of epigenetic age have been linked to life circumstances and health outcomes in older populations. The similarity of these relationships across multiple populations in well-harmonized data has not been addressed. We examine links between epigenetic age, based on currently widely used indicators and key health outcomes in the Republic of Ireland, the United States, and Northern Ireland with harmonized, nationally representative data on their populations age 50 and older. Methods Data from 6,336 participants from the Irish Longitudinal Study on Ageing (TILDA), the Health and Retirement Study of the United States (HRS) and the Northern Ireland COhort for the Longitudinal study of Ageing (NICOLA) are used to investigate the association of accelerated epigenetic age based on three clocks (PhenoAge, GrimAge and DunedinPACE) with four health outcomes (mobility, grip strength, cognitive functioning, and mortality). Importantly, survey questions, population characteristics, and analysis pipelines are harmonized, and similar metrics are used for each health outcome. Results The three countries are remarkably similar in interrelationships among the clocks and in how the clocks relate to health outcomes across the three countries. These second- and third-generation clocks are significantly related to mortality, cognitive loss, strength, and mobility in the three countries. Conclusions For these three countries, epigenetic clocks appear to be highly comparable in their associations with aging health outcomes that reflect physical and cognitive functioning and mortality suggesting they capture a fundamental aging process.