As a member of the Sirtuins family in mammals, SIRT7 locates in nucleus and is a highly specific H3K18Ac (acetylated lysine 18 of histone H3) deacetylase. Recent studies showed that SIRT7 could participate in the ribosomal RNA transcription, cell metabolism, cell stress and DNA damage repair through various signaling pathways. In addition, SIRT7 is also closely related with aging, heart disease and fatty liver. In particular, SIRT7 plays important roles in the regulation of initiation and development of various tumors, such as liver cancer, gastric cancer, breast cancer, bladder cancer, colorectal cancer, and head/neck squamous cell carcinoma. This review describes the cellular and molecular functions of SIRT7, and systematically summarizes recent progress of SIRT7 in human disease.
Animals ; Histones ; Humans ; Lysine ; Neoplasms ; Signal Transduction ; Sirtuins ; metabolism

Aging ; Cellular Senescence ; Heterochromatin ; Humans ; Sirtuins ; genetics ; Stem Cells

SIRT3, SIRT4 and SIRT5 are located in mitochondria and also known as mitochondrial sirtuins. They play important roles in regulating many cellular functions including cell survival, cell cycle or apoptosis, DNA repair and metabolism. Mitochondrial sirtuins are involved in the protection of mitochondrial integrity and energy metabolism under stress regulating the expression of neurotransmitter receptors, neurotrophins, extracellular matrix proteins and various transcription factors, thus involved in epileptogenesis triggered by both genetic or acquired factors. Here we review research progress on the actions of mitochondrial sirtuin in epilepsy; and discuss the challenges and perspectives of mitochondrial sirtuin as a potential therapeutic target for epilepsy.
Apoptosis ; Epilepsy/genetics* ; Humans ; Mitochondria/genetics* ; Sirtuin 3 ; Sirtuins

The sirtuins (SIRTs) are protein-modifying enzymes that are distributed ubiquitously in all organisms. SIRT1 is a mammalian homologue of yeast nicotinamide-adenine-dinucleotide-dependent deacetylase silent information regulator 2 (known as Sir2), which is the best-characterized SIRT family member. It regulates longevity in several model organisms and is involved in several processes in mammalian cells including cell survival, differentiation, and metabolism. SIRT1 induction, either by SIRT-activating compounds such as resveratrol, or metabolic conditioning associated with caloric restriction, could have neuroprotective qualities and thus delay the neurodegenerative process, thereby promoting longevity. However, the precise mechanistic liaison between the activation of SIRT and extended healthy aging or delaying age-related diseases in humans has yet to be established.
Aging ; Caloric Restriction ; Cell Survival ; Humans ; Longevity ; Neurodegenerative Diseases ; Sirtuins ; Stilbenes ; Yeasts

Ageing is the most significant risk factor for a range of prevalent diseases, including cancer, cardiovascular disease, and diabetes. Accordingly, interventions are needed for delaying or preventing disorders associated with the ageing process, i.e., promotion of healthy ageing. Calorie restriction is the only nongenetic and the most robust approach to slow the process of ageing in evolutionarily divergent species, ranging from yeasts, worms, and flies to mammals. Although it has been known for more than 80 years that calorie restriction increases lifespan, a mechanistic understanding of this phenomenon remains elusive. Yeast silent information regulator 2 (Sir2), the founding member of the sirtuin family of protein deacetylases, and its mammalian homologue Sir2-like protein 1 (SIRT1), have been suggested to promote survival and longevity of organisms. SIRT1 exerts protective effects against a number of age-associated disorders. Caloric restriction increases both Sir2 and SIRT1 activity. This review focuses on the mechanistic insights between caloric restriction and Sir2/SIRT1 activation. A number of molecular links, including nicotinamide adenine dinucleotide, nicotinamide, biotin, and related metabolites, are suggested to be the most important conduits mediating caloric restriction-induced Sir2/SIRT1 activation and lifespan extension.
Biotin ; Caloric Restriction* ; Cardiovascular Diseases ; Diptera ; Humans ; Longevity ; Mammals ; NAD ; Negotiating ; Niacinamide ; Risk Factors ; Sirtuins ; Yeasts

Sirtuins (SIRTs) are involved in multiple cellular processes. And they are involved in cellular pathways related aging, cancer, and a variety of cellular functions including cell cycle, DNA repair and proliferation. Also they modulate life span. Stem cells have the ability to self-renew for unlimited proliferation and differentiate into various cell types. It has been a little known that the mutation of undifferentiated stem cells in tissue may result in the development of cancer cells by genotoxic carcinogens. Therefore, this study investigated whether some carcinogenic compounds can modulate the expression of sirtuin mRNA on human adipose-derived stem cells. Adipose-derived stem cells (ADSC) were exposed to genotoxic carcinogenic compound (2-nitrofluorene, 2NF) and non-genotoxic carcinogenic compound (clonidine, CND) for 24 hours, 48 hours, 72 hours and 96 hours. The expression of SIRT1 mRNA increased on 72 hours. Expressions of SIRT2 and SIRT7 mRNA increased robustly on 48 hours. But all of SIRTs decreased to a level before a treatment of genotoxic compound on adipose-derived stem cells. These results demonstrated that a treatment of genotoxic compound induced the expression of SIRT mRNA only in the short time. But their level returned to untreated cells on 96 hours. They suggest that the possibility that the sirtuins can retard the carcinogenesis of adipose derived stem cells.
Aging ; Carcinogenesis ; Carcinogens ; Cell Cycle ; Clonidine* ; DNA Repair ; Humans ; RNA, Messenger* ; Sirtuins ; Stem Cells*

As a member of the sirtuins family, also called Class III histone deacetylases (HDACs), SIRT6 has many catalytic enzyme activities and plays a pivotal role in biological processes including anti-aging, chromatin regulation, transcriptional control, glucose and lipid metabolism, and DNA damage repair. Recently, increasing evidences indicated that SIRT6 was related to initiation and development of tumors, such as hepatic cancer, lung cancer, breast cancer and genital system tumors. However, SIRT6 might play a dual role in tumorigenesis and progression. SIRT6 often acted as a tumor suppressor, but might play an oncogenic role. Based on our current study, we depicted the essential roles of SIRT6 in the initiation and progression of various tumors, and summarized its mode of actions, which might provide clues for cancer therapy.
Carcinogenesis ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Neoplasms ; genetics ; pathology ; Oncogenes ; Sirtuins ; genetics ; metabolism

Animals ; Bacterial Infections/metabolism* ; Glucose/metabolism* ; Homeostasis ; Insulin Secretion ; Mice ; Mice, Knockout ; Sirtuins/metabolism*

Silent information regulator 1 (SIRT1) is one of the seven mammalian proteins of the sirtuin family of NAD⁺-dependent deacetylases. SIRT1 plays a pivotal role in neuroprotection and ongoing research has uncovered a mechanism by which SIRT1 may exert a neuroprotective effect on Alzheimer's disease (AD). Growing evidence demonstrates that SIRT1 regulates many pathological processes including amyloid-β precursor protein (APP) processing, neuroinflammation, neurodegeneration, and mitochondrial dysfunction. SIRT1 has recently received enormous attention, and pharmacological or transgenic approaches to activate the sirtuin pathway have shown promising results in the experimental models of AD. In the present review, we delineate the role of SIRT1 in AD from a disease-centered perspective and provides an up-to-date overview of the SIRT1 modulators and their potential as effective therapeutics in AD.
Animals ; Alzheimer Disease ; Amyloid beta-Protein Precursor ; Animals, Genetically Modified ; Sirtuin 1 ; Sirtuins ; Humans

Circadian clocks regulate behavioral, physiological and biochemical processes in a day/night cycle. Circadian oscillators have an essential role in the coordination of physiological processes with the cyclic changes in the physical environment. Such mammalian circadian clocks composed of the positive components (BMAL1 and CLOCK) and the negative components (CRY and PERIOD (PER)) are regulated by a negative transcriptional feedback loop in which PER is rate-limiting for feedback inhibition. In addition, posttranslational modification of these components is critical for setting or resetting the circadian oscillation. Circadian regulation of metabolism is mediated through reciprocal signaling between the clock and metabolic regulatory networks. AMP-activated protein kinase (AMPK) in the brain and peripheral tissue is a crucial cellular energy sensor that has a role in metabolic control. AMPK-mediated phosphorylation of CRY and Casein kinases I regulates the negative feedback control of circadian clock by proteolytic degradation. AMPK can also modulate the circadian rhythms through nicotinamide adenine dinucleotide-dependent regulation of silent information regulator 1. Growing evidence elucidates the AMPK-mediated controls of circadian clock in metabolic diseases such as obesity and diabetes. In this review, we summarize the current comprehension of AMPK-mediated regulation of the circadian rhythms. This will provide insight into understanding how their components regulate the metabolism.
AMP-Activated Protein Kinases/*metabolism ; Animals ; Casein Kinase I/metabolism ; *Circadian Clocks ; Cryptochromes/metabolism ; Humans ; *Metabolism ; Sirtuins/metabolism