Sugrue Victoria J, Prescott Melanie, Glendining Kelly A, Bond Donna M, Horvath Steve, Anderson Greg M, Garratt Michael, Campbell Rebecca E, Hore Timothy A
Department of Anatomy, University of Otago, Dunedin 9016, New Zealand.
Department of Physiology, University of Otago, Dunedin 9016, New Zealand.
Proc Natl Acad Sci U S A. 2025 Jan 21;122(3):e2420087121. doi: 10.1073/pnas.2420087121. Epub 2025 Jan 13.
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 DNA methylation change because it can be precisely enhanced and halted using small molecule manipulation with few additional effects on the cell.
衰老 是一个复杂的过程，其特征是生物功能衰退以及细胞发生广泛的分子改变，包括DNA甲基化变化。在本研究中，我们使用一种男性特有的衰老表观遗传标记构建了一个表观遗传预测指标，用于测量绵羊和小鼠长期雄激素暴露情况（中位绝对误差分别为4.3个月和1.4个月）。我们将这个预测指标称为雄激素时钟，并表明其“滴答”运转由雄激素受体介导，通过给雌性小鼠补充二氢睾酮，雄激素时钟的运转速度可超过正常雄性小鼠。相反，通过阉割去除绵羊体内的雄激素会使雄激素时钟完全停止。除了在医学和农业方面的潜在应用外，我们预测雄激素时钟将成为理解与年龄相关的DNA甲基化变化机制和过程的有用模型，因为通过小分子操作可以精确地加速或停止其运转，且对细胞几乎没有额外影响。
