TY - JOUR
T1 - DNA repair in species with extreme lifespan differences
AU - MacRae, Sheila L.
AU - Croken, Matthew Mc Knight
AU - Calder, R. B.
AU - Aliper, Alexander
AU - Milholland, Brandon
AU - White, Ryan R.
AU - Zhavoronkov, Alexander
AU - Gladyshev, Vadim N.
AU - Seluanov, Andrei
AU - Gorbunova, Vera
AU - Zhang, Zhengdong D.
AU - Vijg, Jan
N1 - Publisher Copyright:
© MacRae et al.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Aging
KW - DNA repair
KW - Genome maintenance
KW - Longevity
KW - Naked mole rat
KW - RNA-seq
KW - Transcriptome
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U2 - 10.18632/aging.100866
DO - 10.18632/aging.100866
M3 - Article
C2 - 26729707
AN - SCOPUS:84958155266
SN - 1945-4589
VL - 7
SP - 1171
EP - 1184
JO - Aging
JF - Aging
IS - 12
ER -