[The effect of ablation of the gene for H+-Transporting NAD/NADP transhydrogenase on the life spans of nematodes and mammals].
Mitochondrial transhydrogenase catalyzes the reaction H(+)(out) + NADP(+) + NADH = NAD(+) + NADPH + H(+)(in). The maintenance of the NADPH pool increases the mitochondrial antioxidant potential. Therefore, according to the commonly adopted free radical theory of aging, ablation of the transhydrogenase gene should reduce the life span. However, contrary to this reasoning, the life span of Caenorhabditis elegans nematodes with null mutations in the gene does not differ from that in wild-type worms. This fact indicates that free radical damage of mitochondria is not associated with aging. Meta analysis of data on the life span in mice possessing a spontaneous mutation in the transhydrogenase gene shows that a lack of this enzyme does not accelerate aging in mammals either. The heart is the tissue with the highest transhydrogenase production rate, and it is likely that this enzyme contributes to the protection of cardiac myocytes from oxidative stress.
Pestov
N B
NB
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Shakhparonov
M I
MI
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D008136:Longevity / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009206:Myocardium / Q000201:enzymology; D032383:Myocytes, Cardiac / Q000201:enzymology; D009250:NADP Transhydrogenases / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D029742:Caenorhabditis elegans Proteins; D009250:NADP Transhydrogenases