Abstract Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies. 

/pdf/the-sirtuin-family-in-health-and-disease-3ofxdg91.pdf

The sirtuin family in health and disease

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by glucose metabolic disturbance. A number of transcription factors and coactivators are involved in this process. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is an important transcription coactivator regulating cellular energy metabolism. Accumulating evidence has indicated that PGC-1α is involved in the regulation of T2DM. Therefore, a better understanding of the roles of PGC-1α may shed light on more efficient therapeutic strategies. Here, we review the most recent progress on PGC-1α and discuss its regulatory network in major glucose metabolic tissues such as the liver, skeletal muscle, pancreas and kidney. The significant associations between PGC-1α polymorphisms and T2DM are also discussed in this review.

https://joe.bioscientifica.com/downloadpdf/journals/joe/229/3/R99.pdf

PGC-1α, glucose metabolism and type 2 diabetes mellitus.

Omega-3 polyunsaturated fatty acids suppress the inflammatory responses of lipopolysaccharide-stimulated mouse microglia by activating SIRT1 pathways.

The tight coordination between mitochondrial biogenesis and mitophagy can be dysregulated during aging, critically influencing whole-body metabolism, health, and lifespan. To date, caloric restriction (CR) appears to be the most effective intervention strategy to improve mitochondrial turnover in aging organisms. The development of pharmacological mimetics of CR has gained attention as an attractive and potentially feasible approach to mimic the CR phenotype. Polyphenols, ubiquitously present in fruits and vegetables, have emerged as well-tolerated CR mimetics that target mitochondrial turnover. Here, we discuss the molecular mechanisms that orchestrate mitochondrial biogenesis and mitophagy, and we summarize the current knowledge of how CR promotes mitochondrial maintenance and to what extent different polyphenols may mimic CR and coordinate mitochondrial biogenesis and clearance.

Polyphenols as Caloric Restriction Mimetics Regulating Mitochondrial Biogenesis and Mitophagy

Pinolenic acid ameliorates oleic acid-induced lipogenesis and oxidative stress via AMPK/SIRT1 signaling pathway in HepG2 cells.

The AMPK-SIRT signaling network regulates glucose tolerance under calorie restriction conditions.

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The AMPK-SIRT signaling network regulates glucose tolerance under calorie restriction conditions.