4.5 Article

Life span is related to the free energy of mitochondrial DNA

Journal

MECHANISMS OF AGEING AND DEVELOPMENT
Volume 126, Issue 10, Pages 1123-1129

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2005.05.003

Keywords

mtDNA; longevity; DNA denaturing; DNA bubbles; DNA free energy; DNA strand separation

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Broadly speaking, the mitochondrial theory of aging relates aging to the rate of damage to mitochondria. In his work, I concentrate on a DNA sequence property, the free energy, which can be interpreted as a factor in the susceptibility of mitochondrial DNA (mtDNA) to mutation. I show that life spans across a broad range of species are a function of the mtDNA free energy and are proportional to the probability of opening of bubbles of single-stranded mtDNA of approximately 20 base pairs in length, in agreement with the measured nucleation size of these bubbles. These transient separations of the mtDNA strands are a possible aging mechanism, through increased mtDNA mutations. In comparisons of species with similar life spans, avian rntDNA has more negative free energy than does mammal, an mtDNA, suppressing the predicted probability of mtDNA bubble formation in birds by over 80% and thus protecting them against mutation. Based on these results I propose three hypotheses about the conflicting evolutionary forces that have acted on the free energy of mtDNA. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

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