Mitochondrial base excision repair positively correlates with longevity in the liver and heart of mammals


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Gredilla Diaz, Ricardo and Sánchez-Román Rojas, Inés and Gómez Rodríguez, Alexia and López Torres, Mónica and Barja de Quiroga, Gustavo (2020) Mitochondrial base excision repair positively correlates with longevity in the liver and heart of mammals. GeroScience, 42 . pp. 653-665. ISSN 2509-2723

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Damage to DNA is especially important for aging. High DNA repair could contribute, in principle, to lower such damage in long-lived species. However, previous studies showed that repair of endogenous damage to nuclear DNA (base excision repair, BER) is negatively or not correlated with mammalian longevity. However, we hypothesize here that mitochondrial, instead of nuclear, BER is higher in long-lived than in short-lived mammals. We have thus measured activities and/or protein levels of various BER enzymes including DNA glycosylases, NTHL1 and NEIL2, and the APE endonuclease both in total and mitochondrial liver and heart fractions from up to eight mammalian species differing by 13-fold in longevity. Our results show, for the first time, a positive correlation between (mitochondrial) BER and mammalian longevity. This suggests that the low steady-state oxidative damage in mitochondrial DNA of long-lived species would be due to both their lower mitochondrial ROS generation and their higher mitochondrial BER. Long-lived mammals do not need to continuously maintain high nuclear BER levels because they release less mitROS to the cytosol. This can be the reason why they tend to show lower nuclear BER values. The higher mitochondrial BER of long-lived mammals contributes to their superior longevity, agrees with the updated version of the mitochondrial free radical theory of aging, and indicates the special relevance of mitochondria and mitROS for aging.

Item Type:Article
Uncontrolled Keywords:Mitochondria, DNA repair, AP endonuclease, DNA glycosylases, aging
Subjects:Medical sciences > Biology > Genetics
Medical sciences > Biology > Mammals
ID Code:62362
Deposited On:01 Oct 2020 13:38
Last Modified:01 Oct 2020 13:38

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