期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 20, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/ijms20102601
关键词
rat liver; longevity; mtDNA content; mtDNA common deletion; TFAM binding; 8-oxodG incidence
资金
- MIUR-FFABR
- Istituto Banco di Napoli-Fondazione
- Innovative Medicine Initiative-Joint Undertaking (IMI-JU) [115621]
- nonprofit research foundation Centro Studi Achille e Linda Lorenzon
While mitochondrial dysfunction is acknowledged as a major feature of aging, much less is known about the role of mitochondria in extended longevity. Livers from aged (28-month-old) and extremely aged (32-month-old) rats were analyzed for citrate synthase activity, mitochondrial transcription factor A (TFAM) amount, mitochondrial DNA (mtDNA), and 4.8 Kb common deletion contents. None of the assayed parameters differed significantly between age groups. TFAM-binding to mtDNA and the incidence of 8-oxo-deoxyguanosine in specific mtDNA regions, encompassing the origins of mtDNA replication (D-loop and Ori-L) and the 16-bp long direct repeat 1 (DR1) of the 4.8 Kb deletion, were determined. A decrease in TFAM binding was unveiled at all regions in extremely aged in comparison with aged rats. Reduced incidence of oxidized purines at all assayed regions was detected in 32-month-old rats compared with the 28-month-old group. A significant positive correlation between the incidence of 8-oxo-deoxoguanosine and TFAM-bound mtDNA was found at D-Loop and Ori-L regions only in 28-month-old rats. The absence of such correlation in 32-month-old rats indicates a different, fine-tuned regulation of TFAM binding in the two age groups and supports the existence of two different paces in aging and extended aging.
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