Aging is associated with widespread changes in genome-wide patterns of DNA methylation. Thousands of CpG sites whose tissue-specific methylation levels are strongly correlated with chronological age have been previously identified; however, the majority of these studies have focused primarily on cosmopolitan populations living in the developed world. It is not known whether age-related patterns of DNA methylation at these loci are similar across a broad range of human genetic and ecological diversity. This issue was addressed in this study of te African Bada of the western Central African rain forest and the Khomani San of the South African Kalahari Desert. The study identified hundreds of CpG sites whose methylation levels are significantly associated with age, thousands that are significant in a meta-analysis; and it replicated trends previously reported in populations of non-African descent. The study confirmed that an age-associated site is the promoter of the gene ELOVL2 shows a remarkably congruent relationship with aging in humans, despite extensive genetic and environmental variation across populations. The study also shows that genotype state at methylation quantitative trait loci (meQTLs) can affect methylation trends at some age-associated CpG sites. This study explored the relationship between CpG methylation and chronological age in populations of African hunter-gatherers who rely on different diets across diverse ecologies. Although many age-related CpG sites replicate across populations, this study indicates that considering common genetic variation at meQTLs further improves the ability to detect previously identified age associations. (Publisher abstract modified)
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