The sirtuin family in health and disease

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.

Inhibition of histone deacetylases attenuates tumor progression and improves immunotherapy in breast cancer

“…It is required to measure the efficacy of HDAC inhibitors in solid tumors ( 130 ). Sirtuins inhibitors, such as nicotinamide, sirtinol and splitomicin, have shown their activities in regulation of metabolism, DNA repair, proliferation, drug resistance and immunotherapy ( 131 ). Due to limited space, we do not discuss the role of sirtuins inhibitors in modulation of breast cancer immunotherapy.…”

Cellular Senescence in Intervertebral Disc Aging and Degeneration: Molecular Mechanisms and Potential Therapeutic Opportunities

“…Sirtuins are closely related to many cellular functions involved in longevity, immune and inflammatory responses, DNA damage repair, etc. [ 97 ]. Of the seven known SIRTs [ 97 ], only a few have been studied in the context of CS and IDD.…”

Role of sirtuins in attenuating plaque vulnerability in atherosclerosis

“…SIRT3 also plays a role in aging and is associated with longevity and it has recently been documented that exercise-induced SIRT3 decreases cellular stress and may contribute to longevity [ 29 ]. Sirtuins are also involved in regulating glucose-6-phosphate dehydrogenase (G6PD) activity (SIRT2), SOD2 activity (SIRT3), suppressing inflammation by suppressing AP-1 signaling (SIRT1, 3, and 6), regulating inflammatory signaling in dendritic cells, which play a critical role in plaque vulnerability, thereby regulating T cells and Tregs cells population (SIRT1), inhibiting NLRP3 inflammasome (SIRT1 and SIRT2), and promoting osteoblast differentiation and bone formation (SIRT1, 6, and 7) [ 10 , 30 , 31 ]. With the important role of sirtuins in inflammation, cellular stress, and aging, it is important to delineate the role of sirtuins in plaque vulnerability as inflammation, cellular stress, and aging are the risk factors in plaque vulnerability and atherosclerosis.…”