Epigenetic Changes in Aging: The Contribution of SIRT1 to Longevity

Aging encompasses the gradual and intrinsic progression of physical, psychological, and functional changes that occur in living organisms over time. In aged organisms, a noticeable reduction in histones levels is accompanied by both local and global chromatin remodeling. This shift creates an imbalance between activating and repressive histone modifications, resulting in widespread transcriptional changes observed in various aging models. Sirtuins, specifically class III NAD+-dependent histone deacetylases (HDAC), play a vital role in modifying various proteins, including histones, due to their deacetylase activity. These enzymes are intricately involved in critical epigenetic modifications and mediate a wide array of biological functions. Their roles encompass the maintenance of genomic stability, metabolism regulation, and apoptosis modulation, impacting the aging process, and even being implicated in tumorigenesis. Sirtuins possess the capability to recruit and activate several enzymes that are part of the epigenetic machinery. This includes DNA methyltransferases (DNMTs), histone acetyltransferases (HATs) and methyltransferases (HMTs). Consequently, sirtuins are pivotal in regulating heterochromatin formation and gene silencing. In addition to their epigenetic roles, sirtuins, particularly SIRT1, also interact with several key proteins, including NF-κB, AMPK, PGC1α, m-TOR, FOXOs and p53. These interactions are associated with various aspects of the aging process. SIRT1, a prominent member of the sirtuin family, has garnered considerable attention for its role in regulating longevity and its potential therapeutic applications in preventing and treating age-related diseases. In this chapter, we will delve into how epigenetic events influence the aging process and explore how SIRT1 can impact on longevity by inducing or modifying various epigenetic changes, including chromatin remodeling and histone acetylation and methylation.