Sirtuins and renal diseases: relationship with aging and diabetic nephropathy.
Sirtuins are members of the Sir2 (silent information regulator 2) family, a group of class III deacetylases. Mammals have seven different sirtuins, SIRT1-SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules. SIRT1 has been the most extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. SIRT1 deficiency under various stress conditions, such as metabolic or oxidative stress or hypoxia, is implicated in the pathophysiologies of age-related diseases including diabetes, cardiovascular diseases, neurodegenerative disorders and renal diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation and fibrosis, and may regulate lipid metabolism, autophagy, blood pressure and sodium balance. Therefore the activation of SIRT1 in the kidney may be a new therapeutic target to increase resistance to many causal factors in the development of renal diseases, including diabetic nephropathy. In addition, SIRT3 and SIRT6 are implicated in age-related disorders or longevity. In the present review, we discuss the protective functions of sirtuins and the association of sirtuins with the pathophysiology of renal diseases, including diabetic nephropathy.
Diabetology and Endocrinology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, Japan.
Munehiro
M
Kitada
Shinji
S
Kume
Ai
A
Takeda-Watanabe
Keizo
K
Kanasaki
Daisuke
D
Koya
D000375:Aging / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D003928:Diabetic Nephropathies / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism; D056566:Sirtuin 3 / Q000378:metabolism; D037761:Sirtuins / Q000378:metabolism*
C447939:SIRT1 protein, human; C466093:SIRT3 protein, human; C516592:SIRT6 protein, human; D056564:Sirtuin 1; D056566:Sirtuin 3; D037761:Sirtuins