Redox-regulating sirtuins in aging, caloric restriction, and exercise

Zsolt Radak, Erika Koltai, Albert W. Taylor, Mitsuru Higuchi, Shuzo Kumagai, Hideki Ohno, Sataro Goto, Istvan Boldogh

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

The consequence of decreased nicotinamide adenine dinucleotide (NAD +) levels as a result of oxidative challenge is altered activity of sirtuins, which, in turn, brings about a wide range of modifications in mammalian cellular metabolism. Sirtuins, especially SIRT1, deacetylate important transcription factors such as p53, forkhead homeobox type O proteins, nuclear factor κB, or peroxisome proliferator-activated receptor γ coactivator 1α (which controls the transcription of pro- and antioxidant enzymes, by which the cellular redox state is affected). The role of SIRT1 in DNA repair is enigmatic, because it activates Ku70 to cope with double-strand breaks, but deacetylation of apurinic/apyrimidinic endonuclease 1 and probably of 8-oxoguanine-DNA glycosylase 1 decreases the activity of these DNA repair enzymes. The protein-stabilizing effects of the NAD+-dependent lysine deacetylases are readily related to housekeeping and redox regulation. The role of sirtuins in caloric restriction (CR)-related longevity in yeast is currently under debate. However, in mammals, it seems certain that sirtuins are involved in many cellular processes that mediate longevity and disease prevention via the effects of CR through the vascular, neuronal, and muscular systems. Regular physical exercise-mediated health promotion also involves sirtuin-regulated pathways including the antioxidant-, macromolecular damage repair-, energy-, mitochondrial function-, and neuronal plasticity-associated pathways. This review critically evaluates these findings and points out the age-associated role of sirtuins.

Original languageEnglish (US)
Pages (from-to)87-97
Number of pages11
JournalFree Radical Biology and Medicine
Volume58
DOIs
StatePublished - May 2013

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Keywords

  • Aging
  • Antioxidants
  • Caloric restriction
  • DNA repair
  • Exercise
  • Free radicals
  • Redox homeostasis
  • Redox signaling
  • Sirtuins

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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