Pathways for ischemic cytoprotection: Role of sirtuins in caloric restriction, resveratrol, and ischemic preconditioning

Kahlilia C. Morris, Hung Wen Lin, John W. Thompson, Miguel A. Perez-Pinzon

Research output: Contribution to journalReview articlepeer-review

103 Scopus citations


Caloric restriction (CR), resveratrol, and ischemic preconditioning (IPC) have been shown to promote protection against ischemic injury in the heart and brain, as well as in other tissues. The activity of sirtuins, which are enzymes that modulate diverse biologic processes, seems to be vital in the ability of these therapeutic modalities to prevent against cellular dysfunction and death. The protective mechanisms of the yeast Sir2 and the mammalian homolog sirtuin 1 have been extensively studied, but the involvement of other sirtuins in ischemic protection is not yet clear. We examine the roles of mammalian sirtuins in modulating protective pathways against oxidative stress, energy depletion, excitotoxicity, inflammation, DNA damage, and apoptosis. Although many of these sirtuins have not been directly implicated in ischemic protection, they may have unique roles in enhancing function and preventing against stress-mediated cellular damage and death. This review will include in-depth analyses of the roles of CR, resveratrol, and IPC in activating sirtuins and in mediating protection against ischemic damage in the heart and brain.

Original languageEnglish (US)
Pages (from-to)1003-1019
Number of pages17
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number4
StatePublished - Apr 2011


  • antioxidants
  • cardiac arrest
  • cell death mechanisms
  • cerebral ischemia
  • mitochondria
  • sirtuins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology


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