Wu Tianhao, You Yingqian, Zhou Yuhan, Hong Shiru, Bai Yansen, Guo Huan
Department of Occupational and Environmental Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Institute for Chemical Carcinogenesis, School of Public Health, Guangzhou Medical University, Guangzhou, China.
J Gerontol A Biol Sci Med Sci. 2025 Sep 19;80(10). doi: 10.1093/gerona/glaf178.
Both mosaic loss of Y chromosome (mLOY) and frailty are related to human aging. However, their relationship and the potential mediating effect of mLOY on the association between frailty and mortality risk remain understudied. A total of 8947 middle-aged and older male adults from the Dongfeng-Tongji cohort were included in this study. Causes of death were tracked till the end of year 2018. Frailty index (FI) was calculated by 34 deficits and categorized into three groups: (1) robust (FI ≤ 0.10), (2) prefrail (0.10 < FI < 0.25), and (3) frail (FI ≥ 0.25). mLOY was estimated by genotyping data and presented as the proportion of leukocytes with mLOY. Cox proportional hazards regressions were used to assess the associations of mLOY with risk of mortality. Mediation effects of mLOY were estimated under a counterfactual-based framework. In this prospective study, the prevalence of prefrail and frail participants were 50.2% and 29.0%, respectively. Compared to the robust participants, frail males exhibited significantly increased level of mLOY [β (95% CI) =1.15 (0.62 to 1.68)]. Frailty and mLOY showed significant associations with increased mortality risks, and mLOY may mediate a separate 27.3, 53.9, and 23.5% of the association of frailty with the risks of death from all causes, cancer, and other causes. These relationships were confined to males aged ≥ 65 years. These findings unveiled the relationships of frailty with mLOY and the mediation role of mLOY in the frailty-mortality association among older males aged ≥ 65 years. Our results highlighted the importance of mLOY during male aging.
Y染色体镶嵌性缺失（mLOY）和身体虚弱均与人类衰老相关。然而，它们之间的关系以及mLOY在身体虚弱与死亡风险关联中的潜在中介作用仍未得到充分研究。本研究纳入了东风-同济队列中的8947名中老年男性成年人。对死亡原因进行追踪直至2018年底。通过34项缺陷计算虚弱指数（FI），并将其分为三组：（1）健康（FI≤0.10），（2）脆弱前期（0.10＜FI＜0.25），以及（3）虚弱（FI≥0.25）。通过基因分型数据估算mLOY，并将其表示为存在mLOY的白细胞比例。采用Cox比例风险回归评估mLOY与死亡风险的关联。在基于反事实的框架下估算mLOY的中介作用。在这项前瞻性研究中，脆弱前期和虚弱参与者的患病率分别为50.2%和29.0%。与健康参与者相比，虚弱男性的mLOY水平显著升高[β（95%CI）=1.15（0.62至1.68）]。身体虚弱和mLOY与死亡风险增加显著相关，并且mLOY可能分别介导了身体虚弱与全因死亡、癌症死亡和其他原因死亡风险关联的27.3%、53.9%和23.5%。这些关系仅限于年龄≥65岁的男性。这些发现揭示了身体虚弱与mLOY的关系以及mLOY在年龄≥65岁老年男性身体虚弱-死亡关联中的中介作用。我们的结果强调了mLOY在男性衰老过程中的重要性。
