LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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Detail(s)
Original language | English |
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Article number | 110038 |
Journal / Publication | Cell Reports |
Volume | 37 |
Issue number | 8 |
Online published | 23 Nov 2021 |
Publication status | Published - 23 Nov 2021 |
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DOI | DOI |
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Link to Scopus | https://www.scopus.com/record/display.uri?eid=2-s2.0-85119419810&origin=recordpage |
Permanent Link | https://scholars.cityu.edu.hk/en/publications/publication(414cae22-ebce-4aba-8ff1-9a54e8e0a668).html |
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.
In: Cell Reports, Vol. 37, No. 8, 110038, 23.11.2021.
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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