Epigenetic Mechanisms of Longevity and Aging

Abstract

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, tissues, 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.

Copyright © 2016 Elsevier Inc. All rights reserved.

Figures

Figure 1. The epigenetic hallmarks of senescence and aging

Senescence and aging are characterized by (A) loss of histones, (B) imbalance of activating and repressive modifications, (C) transcriptional changes, (D) losses and gains in heterochromatin, (E) breakdown of nuclear lamina, (F) global hypomethylation and focal hypermethylation and (G) chromatin remodeling. These changes are heavily dictated by (H) environmental stimuli (I) and nutrient availability that in turn (J) alter intracellular metabolite concentrations.