Cross-sectional and Longitudinal Relationship between Sex Hormones and Six Epigenetic Clocks in Older Adults: Results of the Berlin Aging Study II (BASE-II)

Schmid, H., Vetter, V. M., Homann, J., Bahr, V., Lill, C. M., Regitz-Zagrosek, V., Bertram, L., Demuth, I.

Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health, Regenerat · medrxiv

Paper

Abstract

BackgroundBeyond their essential roles in regulating reproduction and development, sex hormones play a crucial role in the aging processes. Observational studies have indicated that low sex hormone concentrations in older age are associated with adverse health events. DNA methylation age acceleration (DNAmAA) estimated from epigenetic clocks quantifies differences in biological aging. DNAmAA was previously shown to be associated with age at menopause, ovariectomy, hormone replacement therapy and testosterone level.

MethodsWe analysed the relationship between estradiol, dehydroepiandrosterone sulfate (DHEAS) and the Free Androgen Index (FAI) with DNAmAA estimators from six epigenetic clocks (Horvaths, Hannums, 7-CpG clock, PhenoAge, GrimAge, DunedinPACE) in 1,404 participants of the Berlin Aging Study II (BASE-II, mean age at baseline 68.7 {+/-}3.7 years, 48% women). The relationship was investigated in multiple linear regression models cross- sectionally at two time points and longitudinally over on average 7.3 years of follow-up.

ResultsWe did not observe any consistent associations between the sex hormones and DNAmAA estimators investigated. However, we found several nominal associations (alpha=0.05) of unclear relevance. For instance, we identified an inverse association between DHEAS and Horvaths DNAmAA, i.e. a reduced biological age with higher DHEAS levels in men at baseline. In women we found an inverse association between estradiol and DunedinPACE (baseline) and a positive association with GrimAge (follow-up). In longitudinal analyses, {Delta}DHEAS and {Delta}DunedinPACE were inversely associated in both sexes.

ConclusionsOur results suggest that sex hormones play at best a minor role with respect to biological aging in the older population studied here.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper investigates the relationship between sex hormones and biological aging as measured by epigenetic clocks, which is relevant to understanding the mechanisms of aging. However, the findings suggest that sex hormones play a minor role in biological aging, indicating that the research does not provide significant new insights or solutions to the root causes of aging. The nominal associations found are of unclear relevance, limiting the overall impact of the study.

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