Frailty, mosaic loss of Y chromosome, and mortality in older Chinese males

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.