Epigenetic changes during aging and their reprogramming potential

Abstract

The aging process results in significant epigenetic changes at all levels of chromatin and DNA organization. These include reduced global heterochromatin, nucleosome remodeling and loss, changes in histone marks, global DNA hypomethylation with CpG island hypermethylation, and the relocalization of chromatin modifying factors. Exactly how and why these changes occur is not fully understood, but evidence that these epigenetic changes affect longevity and may cause aging, is growing. Excitingly, new studies show that age-related epigenetic changes can be reversed with interventions such as cyclic expression of the Yamanaka reprogramming factors. This review presents a summary of epigenetic changes that occur in aging, highlights studies indicating that epigenetic changes may contribute to the aging process and outlines the current state of research into interventions to reprogram age-related epigenetic changes.

Keywords:

• Aging
• epigenetics
• clock
• chromatin
• histones
• reprogramming
• sirtuins
• DNA methylation

Disclosure statement

D.A.S. is a founder, equity owner, advisor to, director of, consultant to, investor in and/or inventor on patents licensed to Vium, Jupiter Orphan Therapeutics, Cohbar, Galilei Biosciences, GlaxoSmithKline, OvaScience, EMD Millipore, Wellomics, Inside Tracker, Caudalie, Bayer Crop Science, Longwood Fund, Zymo Research, EdenRoc Sciences (and affiliates Arc-Bio, Dovetail Genomics, Claret Bioscience, Revere Biosensors, UpRNA and MetroBiotech (an NAD booster company), Liberty Biosecurity). Life Biosciences (and affiliates Selphagy, Senolytic Therapeutics, Spotlight Biosciences, Animal Biosciences, Iduna, Immetas, Continuum Biosciences, Jumpstart Fertility (an NAD booster company), and Lua Communications). Iduna is a cellular reprogramming company, partially owned by Life Biosciences. DS sits on the board of directors of both companies. D.A.S. is an inventor on a patent application filed by Mayo Clinic and Harvard Medical School that has been licensed to Elysium Health; his personal share is directed to the Sinclair lab. For more information see https://genetics.med.harvard.edu/sinclair-test/people/sinclair-other.php. A.E.K. has no conflicts to declare.

Additional information

Funding

This work was supported by the Glenn Foundation for Medical Research and grants from the NIH (R37 AG028730, R01 AG019719 and R01 DK100263), and Epigenetics Seed Grant (601139_2018) from Department of Genetics, Harvard Medical School. A.E.K is supported by an NHMRC CJ Martin biomedical fellowship (GNT1122542).