DNA repair in species with extreme lifespan differences

Sheila L. MacRae, Matthew McKnight Croken, R. B. Calder, Alexander Aliper, Brandon Milholland, Ryan R. White, Alexander Zhavoronkov, Vadim N. Gladyshev, Andrei Seluanov, Vera Gorbunova, Zhengdong Zhang, Jan Vijg

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1171-1184
Number of pages14
JournalAging
Volume7
Issue number12
StatePublished - 2015

Fingerprint

DNA Repair
Mole Rats
Transcriptome
Genes
Genomics
DNA Damage
Ecosystem
Life Style
Mammals
Up-Regulation
Maintenance
Genome
Liver

Keywords

  • Aging
  • DNA repair
  • Genome maintenance
  • Longevity
  • Naked mole rat
  • RNA-seq
  • Transcriptome

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

MacRae, S. L., Croken, M. M., Calder, R. B., Aliper, A., Milholland, B., White, R. R., ... Vijg, J. (2015). DNA repair in species with extreme lifespan differences. Aging, 7(12), 1171-1184.

DNA repair in species with extreme lifespan differences. / MacRae, Sheila L.; Croken, Matthew McKnight; Calder, R. B.; Aliper, Alexander; Milholland, Brandon; White, Ryan R.; Zhavoronkov, Alexander; Gladyshev, Vadim N.; Seluanov, Andrei; Gorbunova, Vera; Zhang, Zhengdong; Vijg, Jan.

In: Aging, Vol. 7, No. 12, 2015, p. 1171-1184.

Research output: Contribution to journalArticle

MacRae, SL, Croken, MM, Calder, RB, Aliper, A, Milholland, B, White, RR, Zhavoronkov, A, Gladyshev, VN, Seluanov, A, Gorbunova, V, Zhang, Z & Vijg, J 2015, 'DNA repair in species with extreme lifespan differences', Aging, vol. 7, no. 12, pp. 1171-1184.
MacRae SL, Croken MM, Calder RB, Aliper A, Milholland B, White RR et al. DNA repair in species with extreme lifespan differences. Aging. 2015;7(12):1171-1184.
MacRae, Sheila L. ; Croken, Matthew McKnight ; Calder, R. B. ; Aliper, Alexander ; Milholland, Brandon ; White, Ryan R. ; Zhavoronkov, Alexander ; Gladyshev, Vadim N. ; Seluanov, Andrei ; Gorbunova, Vera ; Zhang, Zhengdong ; Vijg, Jan. / DNA repair in species with extreme lifespan differences. In: Aging. 2015 ; Vol. 7, No. 12. pp. 1171-1184.
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