The androgen clock is an epigenetic predictor of long- term male hormone exposure

• 成果类型: Article
• 署名作者: Sugrue, Victoria J.; Prescott, Melanie; Glendining, Kelly A.; Bond, Donna M.; Horvath, Steve; Anderson, Greg M.; Garratt, Michael; Campbell, Rebecca E.; Hore, Timothy A.
• 署名单位: University of Otago; University of Otago; University of California System; University of California Los Angeles
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14108
• DOI: 10.1073/pnas.2420087121
• 发表日期: 2025-01-16
• 关键词: life-span; dna methylation; anabolic-steroids; testosterone; mortality; BEHAVIOR; longevity; estradiol; survival; receptor

摘要

Aging is a complex process characterized by biological decline and a wide range of molecular alterations to cells, including changes to DNA methylation. In this study, we used a male- specific epigenetic marker of aging to build an epigenetic predictor that measures long- term androgen exposure in sheep and mice (median absolute error of 4.3 and 1.4 mo, respectively). We term this predictor the androgen clock and show its tick is mediated by the androgen receptor and can be accelerated beyond that in normal male mice by supplementing females with dihydrotestosterone. Conversely, the removal of androgens by castration in sheep completely halted the androgen clock. In addition to potential applications in medicine and agriculture, we predict the androgen clock will prove a useful model to understand the mechanisms and processes of age- associated molecule manipulation with few additional effects on the cell.