Abstract
DNA mutations in somatic cells have been implicated in the causation of aging, with longer-lived species having a higher capacity to maintain genome sequence integrity than shorter-lived species. In an attempt to directly test this hypothesis, we used single-cell whole-genome sequencing to analyze spontaneous and bleomycin-induced somatic mutations in lung fibroblasts of four rodent species with distinct maximum life spans, including mouse, guinea pig, blind mole-rat, and naked mole-rat, as well as humans. As predicted, the mutagen-induced mutation frequencies inversely correlated with species-specific maximum life span, with the greatest difference observed between the mouse and all other species. These results suggest that long-lived species are capable of processing DNA damage in a more accurate way than short-lived species.
| Original language | English (US) |
|---|---|
| Article number | eabj3284 |
| Journal | Science Advances |
| Volume | 7 |
| Issue number | 44 |
| DOIs | |
| State | Published - Oct 2021 |
Bibliographical note
Funding Information:This work is funded by National Institutes of Health grant P01 AG047200 (to V.G., J.V., A.S., and V.N.G.), National Institutes of Health grant K99/R00 AG056656 (to X.D.), National Institutes of Health grant P01 AG017242 (to J.V.), National Institutes of Health grant U01 ES029519 (to J.V.), National Institutes of Health grant U01 HL145560 (to J.V.), and National Institutes of Health grant R01 AG064223 (to V.N.G.), National Institutes of Health grant U19 AG056278 (to J.V.), and the Glenn Foundation for Medical Research (to J.V.).
Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).