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

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • 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
  • Bing Zhang

Related Research Unit(s)

Detail(s)

Original languageEnglish
Article number110038
Journal / PublicationCell Reports
Volume37
Issue number8
Online published23 Nov 2021
Publication statusPublished - 23 Nov 2021

Link(s)

Abstract

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

Research Area(s)

  • aging, atherosclerosis, DNA damage, LARP7, senescence

Citation Format(s)

LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity. / Yan, Pengyi; Li, Zixuan; Xiong, Junhao et al.
In: Cell Reports, Vol. 37, No. 8, 110038, 23.11.2021.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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