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- Title
Differences in Liver TFAM Binding to mtDNA and mtDNA Damage between Aged and Extremely Aged Rats.
- Authors
Chimienti, Guglielmina; Picca, Anna; Fracasso, Flavio; Marzetti, Emanuele; Calvani, Riccardo; Leeuwenburgh, Christiaan; Russo, Francesco; Lezza, Angela Maria Serena; Pesce, Vito
- Abstract
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.
- Subjects
MITOCHONDRIAL DNA; DNA damage; TRANSCRIPTION factors; DEOXYGUANOSINE; LIVER
- Publication
International Journal of Molecular Sciences, 2019, Vol 20, Issue 10, p2601
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms20102601