Low rates of hydrogen peroxide production by isolated heart mitochondria associate with long maximum lifespan in vertebrate homeotherms.

TitleLow rates of hydrogen peroxide production by isolated heart mitochondria associate with long maximum lifespan in vertebrate homeotherms.
Publication TypeJournal Article
Year of Publication2007
AuthorsLambert, AJ, Boysen, HM, Buckingham, JA, Yang, T, Podlutsky, A, Austad, SN, Kunz, TH, Buffenstein, R, Brand, MD
JournalAging Cell
Volume6
Issue5
Pagination607-18
Date Published2007 Oct
ISSN1474-9718
KeywordsAging, Animals, Birds, Electron Transport Complex I, Female, Free Radicals, Hydrogen Peroxide, Longevity, Male, Mammals, Mitochondria, Heart, Reactive Oxygen Species
Abstract

An inverse correlation between free radical production by isolated mitochondria and longevity in homeotherms has been reported, but previous comparative studies ignored possible confounding effects of body mass and phylogeny. We investigated this correlation by comparing rates of hydrogen peroxide (H(2)O(2)) production by heart mitochondria isolated from groups or pairs of species selected to have very different maximum lifespans but similar body masses (small mammals, medium-sized mammals, birds). During succinate oxidation, H(2)O(2) production rates were generally lower in the longer-lived species; the differences arose at complex I of the electron transport chain during reverse electron transport. Additional data were obtained from large species and the final dataset comprised mouse, rat, white-footed mouse, naked mole-rat, Damara mole-rat, guinea pig, baboon, little brown bat, Brazilian free-tailed bat, ox, pigeon and quail. In this dataset, maximum lifespan was negatively correlated with H(2)O(2) production at complex I during reverse electron transport. Analysis of residual maximum lifespan and residual H(2)O(2) production revealed that this correlation was even more significant after correction for effects of body mass. To remove effects of phylogeny, independent phylogenetic contrasts were obtained from the residuals. These revealed an inverse association between maximum lifespan and H(2)O(2) production that was significant by sign test, but fell short of significance by regression analysis. These findings indicate that enhanced longevity may be causally associated with low free radical production by mitochondria across species over two classes of vertebrate homeotherms.

DOI10.1111/j.1474-9726.2007.00312.x
Alternate JournalAging Cell
Citation Key10.1111/j.1474-9726.2007.00312.x
PubMed ID17596208
Grant ListMC_U105663137 / / Medical Research Council / United Kingdom
S06-GM08168 / GM / NIGMS NIH HHS / United States
066750 / / Wellcome Trust / United Kingdom
066750/B/01/Z / / Wellcome Trust / United Kingdom
AG022891-01 / AG / NIA NIH HHS / United States