Sirtuins, epigenetics and longevity

Wątroba, Mateusz; Dudek, Ilona; Skoda, Marta; Stangret, Aleksandra; Rzodkiewicz, Przemysław; Szukiewicz, Dariusz

doi:10.1016/j.arr.2017.08.001

Cited by 171 publications

(110 citation statements)

References 103 publications

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“…SIRT1 is one of the seven isoforms (SIRT1‐7) belonging to the mammalian sirtuins, the third member of the superfamily of the histone deacetylases (HDACs), and its enzymatic activity is dependent to the cofactor nicotinamide adenine dinucleotide (NAD + ). SIRT1, along with the other sirtuins, is involved in many physiological processes such as cell metabolism, regulation of DNA repair, inflammatory response, cell cycle, and apoptosis (Watroba et al, ). Therefore, in these physio‐pathological conditions, the activation of SIRT1 is desirable in order to promote cell response towards endogenous or exogenous stressors.…”

Section: Introductionmentioning

confidence: 99%

The link between the AMPK/SIRT1 axis and a flavonoid‐rich extract of Citrus bergamia juice: A cell‐free, in silico, and in vitro study

Maugeri

Ferlazzo

Luca

et al. 2019

Phytotherapy Research

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A previous report indicated that the flavonoid‐rich extract of bergamot juice (BJe) exerts an anti‐inflammatory effect through the activation of SIRT1 in leukemic monocytes THP‐1 exposed to lipopolysaccharide (LPS). In this study, we deeply investigate the mode of action of BJe, along with its major flavonoids on SIRT1 through cell‐free, in silico, and in vitro experimental models. In the cell‐free assay, all the tested compounds as well as the whole BJe inhibited the deacetylase activity of SIRT1. This finding was reinforced by the results of the in silico study. In THP‐1 cells exposed to LPS, a reduction of SIRT1 activity was observed, effect that was reverted by the pre‐incubation with either BJe or its major flavonoids. This effect was also observed at gene level. Employing an activator and an inhibitor of AMP‐activated protein kinase (AMPK; AICAR and dorsomorphin, respectively), we discovered its involvement in the activation of SIRT1 elicited by BJe or its major flavonoids in whole cell. Our study indicates the dual role of BJe and its components, depending on the employed experimental model as well as reveals their mode of action on the AMPK/SIRT1 axis, suggesting their role as promising candidates in pathologies in which this axis is implied.

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Section: Introductionmentioning

confidence: 99%

The link between the AMPK/SIRT1 axis and a flavonoid‐rich extract of Citrus bergamia juice: A cell‐free, in silico, and in vitro study

Maugeri

Ferlazzo

Luca

et al. 2019

Phytotherapy Research

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“…First described as a chromatin-silencing component, several studies demonstrated its beneficial effects on calorie restriction, health, and longevity in different species [53]. SIRT1 is the human ortholog of Sir2, a nuclear/cytosolic enzyme with an important role on the metabolism, immune response, cell differentiation and cancer, where different studies suggest a role for SIRT1 as a tumor suppressor or as an oncogenic factor on different physiological conditions [12, 50, 54–56]. SIRT1 acts as a lysine deacetylase which has been shown to be an important post-translational modification for cytosolic proteins [57].…”

Section: Discussionmentioning

confidence: 99%

“…Sirtuin proteins are present in the nucleus, cytoplasm and mitochondria. Although initially identified as deacetylases, sirtuins also have shown deacylase and O -ADP-ribosylase activity [12]. SIRT3, SIRT4, and SIRT5 are mitochondrial proteins, while SIRT1, SIRT6 and SIRT7 are nuclear enzymes and can take part in the epigenetic regulation of cell phenotype.…”

Section: Introductionmentioning

confidence: 99%

Expression and genotype-dependent catalytic activity of N-acetyltransferase 2 (NAT2) in human peripheral blood mononuclear cells and its modulation by Sirtuin 1

Salazar‐González

Turiján-Espinoza

Hein

et al. 2018

Biochemical Pharmacology

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N-acetyltransferase 2 (NAT2) catalyzes the biotransformation of numerous arylamine and hydrazine drugs and carcinogens. Genetic polymorphisms of NAT2 modify drug efficacy and toxicity and susceptibility to diseases such as cancer and type 2 diabetes. Expression of NAT2 has been documented in the liver and gastrointestinal tract but not in other tissues. Deacetylation of cytosolic proteins by sirtuins is a post-translational modification important in regulatory networks of diverse cellular processes. The aim of the present study was to investigate NAT2 expression in peripheral blood mononuclear cells (PBMC) and the effects of NAT2 genotype and Sirtuin 1 (SIRT1). Both NAT2 and SIRT1 proteins were expressed on PBMC. Their expression was more prevalent on CD3+ compared to CD19+ and CD56+ cell populations. N-acetylation capacity of PBMC exhibited a NAT2 gene-dose response toward the N-acetylation of isoniazid. Subjects with rapid NAT2 genotype showed an apparent V of 42.1 ± 2.4; intermediate NAT2 genotypes an apparent V of 22.6 ± 2.2; and slow acetylator NAT2 genotypes an apparent V of 19.9 ± 1.7 nM acetyl-isoniazid/24 h/million cells. The N-acetylation capacity of NAT2 in the presence of SIRT1 enhancer was significantly decreased (p < 0.001), conversely, the transient silencing of SIRT1 resulted in an increase of N-acetylation capacity (p < 0.001). These findings are the first report of NAT2 genotype-dependent expression on PBMC and post-translational modification by SIRT1. These findings constitute a substantial advance in our understanding of human N-acetyltransferase expression and a new much less invasive method for measurement of human NAT2 expression and phenotype.

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“…The actions include longevity-promoting effects [14,15], for their ability to inhibit cancer [16,17] and, more recently, because of their involvement in circadian rhythm regulation [18,19,20]. …”

Section: Introductionmentioning

confidence: 99%

Melatonin Mitigates Mitochondrial Meltdown: Interactions with SIRT3

Reíter

Tan

Rosales-Corral

et al. 2018

IJMS

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Melatonin exhibits extraordinary diversity in terms of its functions and distribution. When discovered, it was thought to be uniquely of pineal gland origin. Subsequently, melatonin synthesis was identified in a variety of organs and recently it was shown to be produced in the mitochondria. Since mitochondria exist in every cell, with a few exceptions, it means that every vertebrate, invertebrate, and plant cell produces melatonin. The mitochondrial synthesis of melatonin is not photoperiod-dependent, but it may be inducible under conditions of stress. Mitochondria-produced melatonin is not released into the systemic circulation, but rather is used primarily in its cell of origin. Melatonin’s functions in the mitochondria are highly diverse, not unlike those of sirtuin 3 (SIRT3). SIRT3 is an NAD+-dependent deacetylase which regulates, among many functions, the redox state of the mitochondria. Recent data proves that melatonin and SIRT3 post-translationally collaborate in regulating free radical generation and removal from mitochondria. Since melatonin and SIRT3 have cohabitated in the mitochondria for many eons, we predict that these molecules interact in many other ways to control mitochondrial physiology. It is predicted that these mutual functions will be intensely investigated in the next decade and importantly, we assume that the findings will have significant applications for preventing/delaying some age-related diseases and aging itself.

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Sirtuins, epigenetics and longevity

Cited by 171 publications

References 103 publications

The link between the AMPK/SIRT1 axis and a flavonoid‐rich extract of Citrus bergamia juice: A cell‐free, in silico, and in vitro study

The link between the AMPK/SIRT1 axis and a flavonoid‐rich extract of Citrus bergamia juice: A cell‐free, in silico, and in vitro study

Expression and genotype-dependent catalytic activity of N-acetyltransferase 2 (NAT2) in human peripheral blood mononuclear cells and its modulation by Sirtuin 1

Melatonin Mitigates Mitochondrial Meltdown: Interactions with SIRT3

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