title: DNA repair in species with extreme lifespan differences.
abstract: Differences in DNA repair capacity have been hypothesized to underlie the great range of maximum lifespans among mammals. However, measurements of individual DNA repair activities in cells and animals have not substantiated such a relationship because utilization of repair pathways among animals--depending on habitats, anatomical characteristics, and life styles--varies greatly between mammalian species. Recent advances in high-throughput genomics, in combination with increased knowledge of the genetic pathways involved in genome maintenance, now enable a comprehensive comparison of DNA repair transcriptomes in animal species with extreme lifespan differences. Here we compare transcriptomes of liver, an organ with high oxidative metabolism and abundant spontaneous DNA damage, from humans, naked mole rats, and mice, with maximum lifespans of ~120, 30, and 3 years, respectively, with a focus on genes involved in DNA repair. The results show that the longer-lived species, human and naked mole rat, share higher expression of DNA repair genes, including core genes in several DNA repair pathways. A more systematic approach of signaling pathway analysis indicates statistically significant upregulation of several DNA repair signaling pathways in human and naked mole rat compared with mouse. The results of this present work indicate, for the first time, that DNA repair is upregulated in a major metabolic organ in long-lived humans and naked mole rats compared with short-lived mice. These results strongly suggest that DNA repair can be considered a genuine longevity assurance system.
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Sheila L
authors.initials: SL
authors.lastname: MacRae
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Matthew McKnight
authors.initials: MM
authors.lastname: Croken
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Calder
authors.affiliation: InSilico Medicine, Inc., Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Aliper
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Milholland
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Ryan R
authors.initials: RR
authors.lastname: White
authors.affiliation: InSilico Medicine, Inc., Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zhavoronkov
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
authors.affiliation: Department of Biology, University of Rochester, Rochester, NY 14627, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Seluanov
authors.affiliation: Department of Biology, University of Rochester, Rochester, NY 14627, USA.
authors.forename: Vera
authors.initials: V
authors.lastname: Gorbunova
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Zhengdong D
authors.initials: ZD
authors.lastname: Zhang
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Vijg
mesh_terms: D000818:Animals; D004260:DNA Repair / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008136:Longevity / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D051381:Rats; D013045:Species Specificity; D059467:Transcriptome
keywords: DNA repair; RNA-seq; aging; genome maintenance; longevity; naked mole rat; transcriptome