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Open AccessArticle

The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

1
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Via Orabona 4, 70125 Bari, Italy
2
Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, L.go F. Vito 8, 00168 Rome, Italy
3
Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, 11330 Stockholm, Sweden
4
Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology “S. de Bellis”, Research Hospital, 70013 Castellana Grotte, Italy
5
Department of Aging and Geriatric Research, Institute on Aging, Division of Biology of Aging, University of Florida, Gainesville, FL 32611, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: Joan Roselló-Catafau
Int. J. Mol. Sci. 2021, 22(4), 1665; https://doi.org/10.3390/ijms22041665
Received: 28 December 2020 / Revised: 3 February 2021 / Accepted: 4 February 2021 / Published: 7 February 2021
Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement. View Full-Text
Keywords: rat liver; aging; calorie restriction; mitochondrial biogenesis; mtDNA damage; age-sensitive efficacy of CR rat liver; aging; calorie restriction; mitochondrial biogenesis; mtDNA damage; age-sensitive efficacy of CR
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MDPI and ACS Style

Chimienti, G.; Picca, A.; Fracasso, F.; Russo, F.; Orlando, A.; Riezzo, G.; Leeuwenburgh, C.; Pesce, V.; Lezza, A.M.S. The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver. Int. J. Mol. Sci. 2021, 22, 1665. https://doi.org/10.3390/ijms22041665

AMA Style

Chimienti G, Picca A, Fracasso F, Russo F, Orlando A, Riezzo G, Leeuwenburgh C, Pesce V, Lezza AMS. The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver. International Journal of Molecular Sciences. 2021; 22(4):1665. https://doi.org/10.3390/ijms22041665

Chicago/Turabian Style

Chimienti, Guglielmina; Picca, Anna; Fracasso, Flavio; Russo, Francesco; Orlando, Antonella; Riezzo, Giuseppe; Leeuwenburgh, Christiaan; Pesce, Vito; Lezza, Angela M.S. 2021. "The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver" Int. J. Mol. Sci. 22, no. 4: 1665. https://doi.org/10.3390/ijms22041665

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