Abstract
BackgroundAccelerated age-associated DNA methylation changes in males may explain the earlier onset of age-related diseases (e.g., cardiovascular disease (CVD)) and thus contribute to sexually dimorphic morbidity and lifespan. However, the details regarding the emergence of this sex-biased methylation pattern remain unclear.ResultsTo address these issues, we collected publicly available peripheral blood methylation datasets detected by Illumina HumanMethylation450 BeadChip platform from four studies that contain age and gender information of samples. We analyzed peripheral blood methylation data screened from 708 subjects of European ancestry. Results revealed a significant methylation change acceleration in middle-aged males (40–50 years old), which was further supported by another cohort containing 2711 subjects with Indian ancestry. Additional analyses suggested that these sexually dimorphic methylation changes were significantly overrepresented in genes associated with CVD, which may impact the potential activation of disease expression. Furthermore, we showed that higher prevalence of drinking and smoking in the males has some contribution to the sex-based methylation patterns during aging.ConclusionOur results indicated that the sex-biased methylation changes occurred in middle-aged men in an acceleration manner and likely contribute to the sexual dimorphism observed in human lifespan by promoting the occurrence of CVD. As drinking and smoking were also found to be associated with this accelerated methylation change in men, it is possible that male lifespan may be prolonged by improving unhealthy lifestyles at or before middle age.
Highlights
It is well known that men often live shorter than women [1], which is partly explained by their higher mortality and earlier onset of some age-related diseases, especially cardiovascular disease (CVD) [2, 3]
Accumulated evidence showed that epigenetic changes in aging process are associated with lifespan and age-related diseases including CVD [4,5,6,7], indicating the roles of epigenetic mechanisms in sexually dimorphic lifespan
By analyzing the methylation profile data from 708 healthy individuals, screened by the Illumina HumanMethylation450 BeadChip (Additional file 1: Table S1) [12,13,14], we identified 357 CpGs showing significant sexually dimorphic changes in methylation
Summary
It is well known that men often live shorter than women [1], which is partly explained by their higher mortality and earlier onset of some age-related diseases, especially cardiovascular disease (CVD) [2, 3]. Accumulated evidence showed that epigenetic changes in aging process are associated with lifespan and age-related diseases including CVD [4,5,6,7], indicating the roles of epigenetic mechanisms in sexually dimorphic lifespan. As the well-known epigenetic modification, DNA methylation. Xiao et al Clinical Epigenetics (2018) 10:133. Accelerated age-associated DNA methylation changes in males may explain the earlier onset of agerelated diseases (e.g., cardiovascular disease (CVD)) and contribute to sexually dimorphic morbidity and lifespan. The details regarding the emergence of this sex-biased methylation pattern remain unclear
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