TY - JOUR
T1 - Sirtuin regulation in aging and injury
AU - Poulose, Ninu
AU - Raju, Raghavan
N1 - Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Sirtuins or Sir2 family of proteins are a class of NAD+ dependent protein deacetylases which are evolutionarily conserved from bacteria to humans. Some sirtuins also exhibit mono-ADP ribosyl transferase, demalonylation and desuccinylation activities. Originally identified in the yeast, these proteins regulate key cellular processes like cell cycle, apoptosis, metabolic regulation and inflammation. Humans encode seven sirtuin isoforms SIRT1-SIRT7 with varying intracellular distribution. Apart from their classic role as histone deacetylases regulating transcription, a number of cytoplasmic and mitochondrial targets of sirtuins have also been identified. Sirtuins have been implicated in longevity and accumulating evidence indicate their role in a spectrum of diseases like cancer, diabetes, obesity and neurodegenerative diseases. A number of studies have reported profound changes in SIRT1 expression and activity linked to mitochondrial functional alterations following hypoxic-ischemic conditions and following reoxygenation injury. The SIRT1 mediated deacetylation of targets such as PGC-1α, FOXO3, p53 and NF-κb has profound effect on mitochondrial function, apoptosis and inflammation. These biological processes and functions are critical in life-span determination and outcome following injury. Aging is reported to be characterized by declining SIRT1 activity, and its increased expression or activation demonstrated prolonged life-span in lower forms of animals. A pseudohypoxic state due to declining NAD+ has also been implicated in aging. In this review we provide an overview of studies on the role of sirtuins in aging and injury.
AB - Sirtuins or Sir2 family of proteins are a class of NAD+ dependent protein deacetylases which are evolutionarily conserved from bacteria to humans. Some sirtuins also exhibit mono-ADP ribosyl transferase, demalonylation and desuccinylation activities. Originally identified in the yeast, these proteins regulate key cellular processes like cell cycle, apoptosis, metabolic regulation and inflammation. Humans encode seven sirtuin isoforms SIRT1-SIRT7 with varying intracellular distribution. Apart from their classic role as histone deacetylases regulating transcription, a number of cytoplasmic and mitochondrial targets of sirtuins have also been identified. Sirtuins have been implicated in longevity and accumulating evidence indicate their role in a spectrum of diseases like cancer, diabetes, obesity and neurodegenerative diseases. A number of studies have reported profound changes in SIRT1 expression and activity linked to mitochondrial functional alterations following hypoxic-ischemic conditions and following reoxygenation injury. The SIRT1 mediated deacetylation of targets such as PGC-1α, FOXO3, p53 and NF-κb has profound effect on mitochondrial function, apoptosis and inflammation. These biological processes and functions are critical in life-span determination and outcome following injury. Aging is reported to be characterized by declining SIRT1 activity, and its increased expression or activation demonstrated prolonged life-span in lower forms of animals. A pseudohypoxic state due to declining NAD+ has also been implicated in aging. In this review we provide an overview of studies on the role of sirtuins in aging and injury.
KW - Hypoxia
KW - Ischemia/reperfusion
KW - Mitochondria
KW - SIRT1
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U2 - 10.1016/j.bbadis.2015.08.017
DO - 10.1016/j.bbadis.2015.08.017
M3 - Review article
AN - SCOPUS:84940976163
SN - 0925-4439
VL - 1852
SP - 2442
EP - 2455
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 11
ER -