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

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dc.contributor.authorGredilla Díaz, Ricardo
dc.contributor.authorSánchez-Román Rojas, Inés
dc.contributor.authorGómez Rodríguez, Alexia
dc.contributor.authorLópez Torres, Mónica
dc.contributor.authorBarja De Quiroga Losada, Gustavo
dc.date.accessioned2023-06-16T15:24:33Z
dc.date.available2023-06-16T15:24:33Z
dc.date.issued2020-01-22
dc.description.abstractDamage 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.en
dc.description.departmentDepto. de Genética, Fisiología y Microbiología
dc.description.facultyFac. de Ciencias Biológicas
dc.description.refereedTRUE
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/62362
dc.identifier.citationGredilla Díaz, R., Sánchez-Román Rojas, I., Gómez Rodríguez, A. et al. «Mitochondrial Base Excision Repair Positively Correlates with Longevity in the Liver and Heart of Mammals». GeroScience, vol. 42, n.o 2, abril de 2020, pp. 653-65. DOI.org (Crossref), https://doi.org/10.1007/s11357-020-00158-4.
dc.identifier.doi10.1007/s11357-020-00158-4
dc.identifier.issn2509-2723
dc.identifier.officialurlhttps//doi.org/10.1007/s11357-020-00158-4
dc.identifier.relatedurlhttps://link.springer.com/article/10.1007/s11357-020-00158-4
dc.identifier.urihttps://hdl.handle.net/20.500.14352/6601
dc.journal.titleGeroScience
dc.language.isoeng
dc.page.final665
dc.page.initial653
dc.publisherSpringer
dc.rights.accessRightsrestricted access
dc.subject.cdu577
dc.subject.cdu599
dc.subject.keywordMitochondria
dc.subject.keywordDNA repair
dc.subject.keywordAP endonuclease
dc.subject.keywordDNA glycosylases
dc.subject.keywordaging
dc.subject.ucmGenética
dc.subject.ucmMamíferos
dc.subject.unesco2409 Genética
dc.subject.unesco2401.18 Mamíferos
dc.titleMitochondrial base excision repair positively correlates with longevity in the liver and heart of mammalsen
dc.typejournal article
dc.volume.number42
dspace.entity.typePublication
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relation.isAuthorOfPublication.latestForDiscoverya1e62a87-24dc-4e48-b388-c6b44653870e
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