LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity

• DOI: 10.1016/j.celrep.2021.110038
• Publication Date: 2021-11-23T15:35:28Z
• Authors: Pengyi Yan; Zixuan Li; Junhao Xiong; Zilong Geng; Weiting Wei; Yan Zhang; Gengze Wu; Tao Zhuang; Xiaoyu Tian; Zhijie Liu; Junling Liu; Kun Sun; Fengyuan Chen; Yuzhen Zhang; Chunyu Zeng; Yu Huang; Bing Zhang
• Keywords: Senescence; Sirtuin 1

Cellular senescence is associated with pleiotropic physiopathological processes, including aging and age-related diseases. The persistent DNA damage a major stress leading to senescence, but the underlying molecular link remains elusive. Here, we identify La Ribonucleoprotein 7 (LARP7), 7SK RNA binding protein, as an antagonist. damage-mediated Ataxia Telangiectasia Mutated (ATM) activation triggers extracellular shuttling downregulation of LARP7, which dampens SIRT1 deacetylase activity, enhances p53 NF-κB (p65) transcriptional activity by augmenting their acetylation, thereby accelerates cellular senescence. Deletion LARP7 leads senescent cell accumulation premature in rodent model. Furthermore, show this ATM-LARP7-SIRT1-p53/p65 axis active vascular atherogenesis, preventing its substantially alleviates atherogenesis. Together, study identifies gatekeeper altered pathway plays important role response (DDR)-mediated atherosclerosis.