Epigenetic Regulation of Human Sirtuin 1 Insights into Aging Mechanisms

Sirtuin 1 (SIRT1), a member of the NAD+-dependent deacetylases, plays a pivotal role in epigenetic regulation related to aging. As the most extensively studied sirtuin, SIRT1 influences numerous cellular processes including metabolism, DNA repair, and cell survival, by deacetylating both histone and non-histone proteins. Epigenetic modifications in SIRT1, such as DNA methylation and post-translational histone modifications, have profound effects on gene expression and chromatin structure, contributing to age-related pathologies including metabolic disorders, neurodegeneration, and cancer. SIRT1 also interacts with several transcription factors such as p53 and FOXO, regulating stress responses and cellular senescence. Its activity is modulated by factors such as NAD+ availability and specific activators like resveratrol, which have been explored for their potential to delay aging processes. The role of SIRT1 in promoting longevity is linked to its involvement in the regulation of key pathways like calorie restriction, a well-established method for extending lifespan in various species. Understanding SIRT1's epigenetic mechanisms offers promising therapeutic avenues for addressing aging and associated diseases.