Research Paper|Volume 7, Issue 12|pp 1171—1182

DNA repair in species with extreme lifespan differences

Sheila L MacRae¹, Matthew McKnight Croken¹, R.B Calder¹, Alexander Aliper², Brandon Milholland¹, Ryan R White¹, Alexander Zhavoronkov², Vadim N Gladyshev⁴, Andrei Seluanov³, Vera Gorbunova³, Zhengdong D Zhang¹, Jan Vijg¹

¹Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
²InSilico Medicine, Inc., Johns Hopkins University, Baltimore, MD 21218, USA
³Department of Biology, University of Rochester, Rochester, NY 14627, USA
⁴Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

Received: November 12, 2015Accepted: November 29, 2015Published: December 30, 2015

https://doi.org/10.18632/aging.100866

Copyright: © 2015 MacRae et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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