The age-sensitive efficacy of calorie restriction on mitochondrial biogenesis and mtdna damage in rat liver

Guglielmina Chimienti, Anna Picca, Flavio Fracasso, Francesco Russo, Antonella Orlando, Giuseppe Riezzo, Christiaan Leeuwenburgh, Vito Pesce, Angela Maria Serena Lezza

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number1665
Pages (from-to)1-18
Number of pages18
JournalInternational Journal of Molecular Sciences
Issue number4
Publication statusPublished - Feb 2 2021


  • Age-sensitive efficacy of CR
  • Aging
  • Calorie restriction
  • Mitochondrial biogenesis
  • MtDNA damage
  • Rat liver

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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