Sirtuin 6 (SIRT6) has been in the spotlight of aging research because progeroid phenotypes are associated with SIRT6 deficiency. SIRT6 has multiple molecular functions, including DNA repair and heterochromatin regulation, which position SIRT6 as a hub that regulates genome and epigenome stability. Genomic instability caused by persistent DNA damage and accumulating mutations, together with alterations in the epigenetic landscape and derepression of repetitive genetic elements, have emerged as mechanisms driving organismal aging. Enhanced levels of SIRT6 expression or activity provide avenues for rejuvenation strategies. This review focuses on the role of SIRT6 in the maintenance of genome and epigenome stability and its link to longevity. We propose a model where SIRT6 together with lamins control aging and rejuvenation by maintaining epigenetic silencing of repetitive elements.

Sirtuin 6 (SIRT6) 一直是衰老研究的焦点，因为早衰样表型与 SIRT6 缺陷有关。SIRT6 具有多种分子功能，包括 DNA 修复和异染色质调节，这将 SIRT6 定位为调节基因组和表观基因组稳定性的中枢。由持续的 DNA 损伤和累积突变引起的基因组不稳定性，以及表观遗传景观的改变和重复遗传元素的去抑制，已成为驱动机体衰老的机制。增强的 SIRT6 表达或活性水平为年轻化策略提供了途径。本综述侧重于 SIRT6 在维持基因组和表观基因组稳定性中的作用及其与长寿的联系。