Epigenetic Mechanisms of Longevity and Aging

Abstract

Summary Aging is an inevitable outcome of life, characterized by progressive decline in tissue and organ function and increased risk of mortality. Accumulating evidence links aging to genetic and epigenetic alterations. Given the reversible nature of epigenetic mechanisms, these pathways provide promising avenues for therapeutics against age-related decline and disease. In this review, we provide a comprehensive overview of epigenetic studies from invertebrate organisms, vertebrate models, tissue and in vitro systems. We establish links between common operative aging pathways and hallmark chromatin signatures that can be used to identify “druggable” targets to counter human aging and age-related disease.

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

“…The overall pattern of histone modifications in aging shows a loss of repressive marks and gain of activating marks (Sen, Shah, Nativio, & Berger, 2016). Although it is not known whether such a pattern exists for in human brain aging, thanks to the Roadmap project, a snapshot of the older brain's epigenome in seven brain regions (angular gyrus, anterior caudate, cingulate gyrus, dorsolateral prefrontal cortex, inferior temporal cortex, midhippocampus, and substantia nigra) and six marks (H3K9me3, H3K27me3, H3K4me3, H3K36me3, H3K27ac, and H3K4me1) is available.…”

Targeting chromatin aging - The epigenetic impact of longevity-associated interventions

“…This topic has been the subject of a number of excellent reviews, to which the reader is directed in the following citations (Booth and Brunet, 2016;Brunet and Berger, 2014;Sen et al, 2016).…”

Analysis of DNA modifications in aging research

“…Early efforts sought to examine total levels of DNA methylation and resulted in a theory of genomic hypomethylation (decreased methylation levels across the genome) with aging (Vanyushin et al 1973;Wilson and Jones 1983). While the hypomethylation hypothesis is often referenced as dogma (Zampieri et al 2015;Sen et al 2016), the general consensus has shifted to rejecting this hypothesis based on data from modern quantitative techniques (Unnikrishnan et al 2017a). Thus, the field has moved toward identifying specific genomic sites and regions with differential methylation in animal models (Maegawa et al 2010) and humans (Rakyan et al 2010).…”

“…Given the demonstrated importance of the genetics of aging (Jeck et al 2012), a similar effort is needed to understand how the epigenome changes in response to the various stimuli encountered throughout the lifecycle. Further review of the current state of scientific findings in the epigenomics of aging is beyond the scope of this review, but several recent publications provide an overview of findings in different models and organ systems (Valdes et al 2013;Benayoun et al 2015;Jones et al 2015;Sen et al 2016). The purpose of this review is to examine the technical approaches that can be used in these studies to best meet individual experimental goals and educate geroscience researchers in designing and interpreting epigenomic studies.…”