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Activities of DNA base excision repair enzymes in liver and brain correlate with body mass, but not lifespan

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Abstract

Accumulation of DNA lesions compromises replication and transcription and is thus toxic to cells. DNA repair deficiencies are generally associated with cellular replicative senescence and premature aging syndromes, suggesting that efficient DNA repair is required for normal longevity. It follows that the evolution of increasing lifespan amongst animal species should be associated with enhanced DNA repair capacities. Although UV damage repair has been shown to correlate positively with mammalian species lifespan, we lack similar insight into many other DNA repair pathways, including base excision repair (BER). DNA is continuously exposed to reactive oxygen species produced during aerobic metabolism, resulting in the occurrence of oxidative damage within DNA. Short-patch BER plays an important role in repairing the resultant oxidative lesions. We therefore tested whether an enhancement of BER enzyme activities has occurred concomitantly with the evolution of increased maximum lifespan (MLSP). We collected brain and liver tissue from 15 vertebrate endotherm species ranging in MLSP over an order of magnitude. We measured apurinic/apyrimidinic (AP) endonuclease activity, as well as the rates of nucleotide incorporation into an oligonucleotide containing a single nucleotide gap (catalyzed by BER polymerase β) and subsequent ligation of the oligonucleotide. None of these activities correlated positively with species MLSP. Rather, nucleotide incorporation and oligonucleotide ligation activities appeared to be primarily (and negatively) correlated with species body mass.

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Acknowledgements

MMP was supported by an Ontario Graduate Scholarship. Work at Brock University was supported by the Natural Sciences and Engineering Research Council, the Canada Foundation for Innovation and an Early Researcher Award from the Ontario Ministry of Research and Innovation to JAS. We thank Gary Burness, Esther Tiedke, and Paul Faure for providing bird, livestock, and bat samples.

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  1. Department of Biological Sciences, Brock University, St. Catharines, ON, L2S 3A1, Canada

    Melissa M. Page & Jeffrey A. Stuart

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  1. Melissa M. Page
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Correspondence to Jeffrey A. Stuart.

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Page, M.M., Stuart, J.A. Activities of DNA base excision repair enzymes in liver and brain correlate with body mass, but not lifespan. AGE 34, 1195–1209 (2012). https://doi.org/10.1007/s11357-011-9302-9

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  • DOI: https://doi.org/10.1007/s11357-011-9302-9

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