| Literature DB >> 31002797 |
Xiao Tian1, Denis Firsanov1, Zhihui Zhang1, Yang Cheng2, Lingfeng Luo1, Gregory Tombline1, Ruiyue Tan1, Matthew Simon1, Steven Henderson1, Janine Steffan1, Audrey Goldfarb1, Jonathan Tam1, Kitty Zheng1, Adam Cornwell1, Adam Johnson1, Jiang-Nan Yang3, Zhiyong Mao4, Bruno Manta5, Weiwei Dang6, Zhengdong Zhang7, Jan Vijg7, Aaron Wolfe8, Kelsey Moody8, Brian K Kennedy9, Dirk Bohmann2, Vadim N Gladyshev5, Andrei Seluanov10, Vera Gorbunova11.
Abstract
DNA repair has been hypothesized to be a longevity determinant, but the evidence for it is based largely on accelerated aging phenotypes of DNA repair mutants. Here, using a panel of 18 rodent species with diverse lifespans, we show that more robust DNA double-strand break (DSB) repair, but not nucleotide excision repair (NER), coevolves with longevity. Evolution of NER, unlike DSB, is shaped primarily by sunlight exposure. We further show that the capacity of the SIRT6 protein to promote DSB repair accounts for a major part of the variation in DSB repair efficacy between short- and long-lived species. We dissected the molecular differences between a weak (mouse) and a strong (beaver) SIRT6 protein and identified five amino acid residues that are fully responsible for their differential activities. Our findings demonstrate that DSB repair and SIRT6 have been optimized during the evolution of longevity, which provides new targets for anti-aging interventions.Entities:
Keywords: DNA DSB repair; DNA repair; NER; SIRT6; aging; longevity
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Year: 2019 PMID： 31002797 PMCID： PMC6499390 DOI： 10.1016/j.cell.2019.03.043
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582