Ischemia-reperfusion injury (IRI) remains an unresolved and complicated situation in clinical practice, especially in the case of
organ transplantation. Several factors contribute to its complexity; the depletion of energy during
ischemia and the induction of oxidative stress during reperfusion initiate a cascade of pathways that lead to cell death and finally to severe organ injury. Recently, the
sirtuin family of
nicotinamide adenine dinucleotide-dependent deacetylases has gained increasing attention from researchers, due to their involvement in the modulation of a wide variety of cellular functions. There are seven mammalian
sirtuins and, among them, the nuclear/cytoplasmic
sirtuin 1 (
SIRT1) and the mitochondrial
sirtuin 3 (
SIRT3) are ubiquitously expressed in many tissue types.
Sirtuins are known to play major roles in protecting against cellular stress and in controlling metabolic pathways, which are key processes during IRI. In this review, we mainly focus on
SIRT1 and
SIRT3 and examine their role in modulating pathways against energy depletion during
ischemia and their involvement in oxidative stress, apoptosis, microcirculatory stress and
inflammation during reperfusion. We present evidence of the beneficial effects of
sirtuins against IRI and emphasize the importance of developing new strategies by enhancing their action.