Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Clinical Laboratory Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
Aging Cell. 2022 Mar;21(3):e13563. doi: 10.1111/acel.13563. Epub 2022 Feb 4.
In view of the sex differences in aging-related diseases, sex chromosomes may play a critical role during aging process. This study aimed to identify age-related DNA methylation changes on Y chromosome (ChrY). A two-stage study design was conducted in this study. The discovery stage contained 419 Chinese males, including 205 from the Wuhan-Zhuhai cohort panel, 107 from the coke oven workers panel, and 107 from the Shiyan panel. The validation stage contained 587 Chinese males from the Dongfeng-Tongji sub-cohort. We used the Illumina HumanMethylation BeadChip to determine genome-wide DNA methylation in peripheral blood of the study participants. The associations between age and methylation levels of ChrY CpGs were investigated by using linear regression models with adjustment for potential confounders. Further, associations of age-related ChrY CpGs with all-cause mortality were tested in the validation stage. We identified the significant associations of 41 ChrY CpGs with age at false discovery rate (FDR) <0.05 in the discovery stage, and 18 of them were validated in the validation stage (p < 0.05). Meta-analysis of both stages confirmed the robust positive associations of 14 CpGs and negative associations of 4 CpGs with age (FDR<0.05). Among them, cg03441493 and cg17816615 were significantly associated with all-cause mortality risk [HR(95% CI) = 1.37 (1.04, 1.79) and 0.70 (0.54, 0.93), respectively]. Our results highlighted the importance of ChrY CpGs on male aging.
鉴于与衰老相关的疾病存在性别差异，性染色体在衰老过程中可能发挥关键作用。本研究旨在鉴定 Y 染色体（ChrY）上与年龄相关的 DNA 甲基化变化。本研究采用两阶段研究设计。在发现阶段，包含 419 名中国男性，其中 205 名来自武汉-珠海队列面板，107 名来自焦炉工人面板，107 名来自十堰面板。验证阶段包含 587 名来自东风-同济子队列的中国男性。我们使用 Illumina HumanMethylation BeadChip 来确定研究参与者外周血的全基因组 DNA 甲基化。通过线性回归模型，在调整潜在混杂因素后，研究了年龄与 ChrY CpG 甲基化水平之间的关系。进一步，在验证阶段，研究了与年龄相关的 ChrY CpG 与全因死亡率之间的关联。我们在发现阶段鉴定了与 ChrY 41 个 CpG 与年龄相关的显著关联，在 FDR<0.05 时，在验证阶段，其中 18 个得到了验证（p<0.05）。两个阶段的荟萃分析均证实了 14 个 CpG 与年龄呈正相关，4 个 CpG 与年龄呈负相关（FDR<0.05）。其中，cg03441493 和 cg17816615 与全因死亡率风险显著相关[HR(95% CI) = 1.37 (1.04, 1.79) 和 0.70 (0.54, 0.93)]。我们的研究结果强调了 ChrY CpG 在男性衰老中的重要性。
