Trending with Impact: Epigenetic Shifts Influence Aging and Evolution



July 22, 2021

Aging published this trending theory article on June 16, 2021, entitled, “Shifting epigenetic contexts influence regulatory variation and disease risk” by researchers from the Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, and Broad Institute of MIT and Harvard, Cambridge, MA. Abstract: Epigenetic shifts are a hallmark of aging that impact transcriptional networks at regulatory level. These shifts may modify the effects of genetic regulatory variants during aging and contribute to disease pathomechanism. However, these shifts occur on the backdrop of epigenetic changes experienced throughout an individual’s development into adulthood; thus, the phenotypic, and ultimately fitness, effects of regulatory variants subject to developmental- versus aging-related epigenetic shifts may differ considerably. Natural selection therefore may act differently on variants depending on their changing epigenetic context, which we propose as a novel lens through which to consider regulatory sequence evolution and phenotypic effects. Here, we define genomic regions subjected to altered chromatin accessibility as tissues transition from their fetal to adult forms, and subsequently from early to late adulthood. Based on these epigenomic datasets, we examine patterns of evolutionary constraint and potential functional impacts of sequence variation (e.g., genetic disease risk associations). We find that while the signals observed with developmental epigenetic changes are consistent with stronger fitness consequences (i.e., negative selection pressures), they tend to have weaker effects on genetic risk associations for aging-related diseases. Conversely, we see stronger effects of variants with increased local accessibility in adult tissues, strongest in young adult when compared to old. We propose a model for how epigenetic status of a region may influence the effects of evolutionary relevant sequence variation, and suggest that such a perspective on gene regulatory networks may elucidate our understanding of aging biology. Sign up for free Altmetric alerts about this article - DOI - Full text - Correspondence to: Terence D. Capellini email: Keywords: development, evolution, GWAS, disease, aging About Aging Launched in 2009, Aging publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at​​ or connect with us on: Twitter -​ Facebook -​ SoundCloud -​ YouTube -​ LinkedIn -​ Aging is published by Impact Journals, LLC please visit​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

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