Investigation of DNA Repair in Long-Lived Species

In the open access paper linked below, researchers discuss DNA repair differences between long and short-lived species, a part of the broader debate over the degree to which nuclear DNA damage contributes to degenerative aging beyond the matter of cancer risk. The comparative biology of aging, in which researchers catalog differences in molecular biology between close relative species with large longevity differences, it is often a search for longevity assurance mechanisms. Why is it that the one long-lived species in a collection of similar species is in fact long-lived? When pondering what can be done with that knowledge, it is worth bearing in mind that we are the exceptionally long-lived species in our own family of primates, and thus longevity assurance mechanisms discovered in other groups of mammals may be things that we already possess, not things that can potentially be turned into therapies.

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.

Link: http://www.impactaging.com/papers/v7/n12/full/100866.html

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