Sirtuin 6：将长寿与基因组和表观基因组稳定性联系起来。
Sirtuin 6: linking longevity with genome and epigenome stability.
机构信息
Departments of Biology and Medicine, University of Rochester, Rochester, NY 14627, USA.
Departments of Biology and Medicine, University of Rochester, Rochester, NY 14627, USA.
出版信息
Trends Cell Biol. 2021 Dec;31(12):994-1006. doi: 10.1016/j.tcb.2021.06.009. Epub 2021 Jul 17.
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，因为早衰表型与 SIRT6 缺乏有关。SIRT6 具有多种分子功能，包括 DNA 修复和异染色质调节，这使其成为调节基因组和表观基因组稳定性的中心。持续的 DNA 损伤和积累的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件的去抑制，已成为驱动机体衰老的机制。增强的 SIRT6 表达或活性为复兴策略提供了途径。这篇综述重点介绍了 SIRT6 在维持基因组和表观基因组稳定性及其与长寿的联系中的作用。我们提出了一个模型，其中 SIRT6 与 lamin 一起通过维持重复元件的表观遗传沉默来控制衰老和复兴。
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