Epigenetic Regulation

Epigenetic modifications are heritable changes in gene activity that do not involve changes in the underlying DNA sequence. ^[1] Epigenetics refers to covalent modifications of DNA and core histones that regulate gene activity without altering DNA sequence. ^[2] The term epigenetics was first proposed in 1942. ^[3]

There are four main epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodelling, and noncoding RNA. ^[3] Histone-level control is achieved through covalent biochemical reactions including histone acetylation, histone methylation, and DNA methylation. ^[4] These mechanisms integrate with signaling pathways and transcription factors to orchestrate gene induction. ^[5] Dysregulation of the epigenome drives aberrant transcriptional programs. ^[6]

Aging is accompanied by prominent hallmarks that include genetic and epigenetic alterations. ^[7] These aging-associated epigenetic changes include DNA methylation, histone modification, chromatin remodeling, non-coding RNA regulation, and RNA modification. ^[7] The aging process is associated with altered epigenetic mechanisms of gene regulation such as DNA methylation, histone modification, chromatin remodelling, and non-coding RNAs. ^[8]

The reversible nature of epigenetic alterations positions the epigenetic machinery as a prime target in the discovery of novel therapeutics. ^[1] Understanding epigenetics can be applied clinically through epigenetic biomarkers, epigenetic drugs, and epigenetic editing. ^[3] Partial reprogramming is among the interventions proposed to rejuvenate the epigenome and delay aging. ^[8] Small molecule-based therapies and reprogramming strategies that enable epigenetic rejuvenation have been developed for ameliorating or reversing aging-related conditions. ^[7]