Sex Differences in Epigenetic Signatures of Aging in a Long-Lived Primate
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Date
2023
Authors
Smith, Maili
Journal Title
Journal ISSN
Volume Title
Publisher
University of Oregon
Abstract
Although aging impacts everyone, individuals vary in pace and severity of age-related decline. Many long-lived primates, including humans, exhibit marked variation in aging patterns between males and females. We know that environment can influence the aging process, but it remains unknown how the environment shapes aging at the molecular level. The epigenome, responsive to biological and environmental changes, presents a unique opportunity to explore mechanisms that may influence aging. To better understand sex differences in the aging epigenome in the hippocampus and liver, two tissues responsive to age-related change, we characterized differential DNA methylation due to age in unmatched banked hippocampus (N=88; females=57) and liver (N=94; females=58) samples from rhesus macaques across the lifespan. We found the majority of age-associated sites are indeed sex-specific; only 3% of age-associated sites are shared between sexes in the hippocampus and 21% of age-associated sites are shared in the liver. We found that differentially methylated sites (regardless of sex or tissue type) overwhelmingly lose methylation with increasing age, which is consistent with the genomic hypomethylation hypothesis of aging. Ultimately, characterizing sex differences in how the epigenome changes with age across tissues will help identify how environmental factors interact with molecular mechanisms to shape variation in the rate of aging in long-lived primates.
Description
67 pages
Keywords
epigenetics, aging, dna methylation, sex differences, bioinformatics