A comprehensive review of Sirtuins: With a major focus on redox homeostasis and metabolism

Shahgaldi, Shahab; Kahmini, Fatemeh Rezaei

doi:10.1016/j.lfs.2021.119803

Cited by 52 publications

(38 citation statements)

References 187 publications

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“…Sirtuins (SIRTs) are a family of NAD-dependent protein deacetylases with pleiotropic effects on a variety of key biological processes, including metabolism, cell survival, and aging [ 11 , 12 ]. Of the seven conserved SIRT isotypes (SIRT1–SIRT7), SIRT1, 6, and 7 are principally nuclear, whereas others are mainly located in the cytoplasm (SIRT2) or within mitochondria (SIRT3, 4, and 5) [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Decreased Serum Levels of SIRT1 and SIRT3 Correlate with Severity of Skin and Lung Fibrosis and Peripheral Microvasculopathy in Systemic Sclerosis

Manetti

Rosa

Fioretto

et al. 2022

JCM

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Systemic sclerosis (SSc, scleroderma) is a severe autoimmune connective tissue disease characterized by widespread peripheral microvasculopathy, and progressive cutaneous and visceral fibrosis, leading to significant organ dysfunction. Sirtuins (SIRTs) are a family of NAD-dependent protein deacetylases with pleiotropic effects on a variety of biological processes, including metabolism, cell survival, and aging. In the last decades, increasing studies have explored the contribution of SIRTs to the pathogenesis of SSc, highlighting a significant antifibrotic effect of both SIRT1 and SIRT3. On these bases, the aim of this study was to measure circulating SIRT1 and SIRT3 levels by enzyme-linked immune-sorbent assay in a well-characterized cohort of SSc patients (n = 80) and healthy controls (n = 71), focusing on their possible association with disease clinical features, and their potential as biomarkers reflecting SSc activity and severity. Significantly decreased serum levels of both SIRT1 and SIRT3 were found in SSc patients compared to controls. In SSc, the reduction in circulating SIRT1 and SIRT3 associated with a greater extent of cutaneous fibrosis, presence of interstitial lung disease, and worse pulmonary function. Serum SIRT1 and SIRT3 decrease also correlated with the severity of nailfold microvascular damage, with SIRT3 levels being additionally related to the occurrence of digital ulcers. The levels of these two proteins showed a direct correlation with one another in the circulation of SSc patients. Of the two SIRTs, serum SIRT3 was found to better reflect disease activity and severity in a logistic regression analysis model. Our findings suggest that serum SIRT1 and SIRT3 may represent novel potential biomarkers of increased risk for a more severe, life-threatening SSc disease course.

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Section: Introductionmentioning

confidence: 99%

Decreased Serum Levels of SIRT1 and SIRT3 Correlate with Severity of Skin and Lung Fibrosis and Peripheral Microvasculopathy in Systemic Sclerosis

Manetti

Rosa

Fioretto

et al. 2022

JCM

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“…The family of sirtuins (SIRT-1-SIRT-7), with different cellular localization (nucleus, mitochondria, cytosol), have been associated with longevity. Sirtuin enzymes belongs to class III of histone deacetylases and deacetylate histones and non-histone substrates in a nicotinamide adenine dinucleotide (NAD+)-dependent manner and are thus implicated in the regulation of numerous cellular events including cell cycle control and apoptosis, mitochondrial biogenesis, gene silencing, and genomic stability, thereby mediating longevity [50,51]. Sirtuins are also involved in agerelated processes such as inflammatory responses, as well as in the control of oxidative stress responses [52].…”

Section: Ageing and Inflammationmentioning

confidence: 99%

Impact of Selenium on Biomarkers and Clinical Aspects Related to Ageing. A Review

et al. 2021

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Selenium (Se) is an essential dietary trace element that plays an important role in the prevention of inflammation, cardiovascular diseases, infections, and cancer. Selenoproteins contain selenocysteine in the active center and include, i.e., the enzymes thioredoxin reductases (TXNRD1–3), glutathione peroxidases (GPX1–4 and GPX6) and methionine sulfoxide reductase, involved in immune functions, metabolic homeostasis, and antioxidant defense. Ageing is an inevitable process, which, i.e., involves an imbalance between antioxidative defense and reactive oxygen species (ROS), changes in protein and mitochondrial renewal, telomere attrition, cellular senescence, epigenetic alterations, and stem cell exhaustion. These conditions are associated with mild to moderate inflammation, which always accompanies the process of ageing and age-related diseases. In older individuals, Se, by being a component in protective enzymes, operates by decreasing ROS-mediated inflammation, removing misfolded proteins, decreasing DNA damage, and promoting telomere length. Se-dependent GPX1–4 and TXNRD1–3 directly suppress oxidative stress. Selenoprotein H in the cell nucleus protects DNA, and selenoproteins residing in the endoplasmic reticulum (ER) assist in the removal of misfolded proteins and protection against ER stress. In this review, we highlight the role of adequate Se status for human ageing and prevention of age-related diseases, and further its proposed role in preservation of telomere length in middle-aged and elderly individuals.

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“…Sirtuins can be post-translationally modified and inhibited by many physiological oxidants including nitric oxide (NO), S -nitrosoglutathione (GSNO), hydrogen peroxide (H 2 O 2 ), and peroxynitrite (ONOO – ). The pathophysiological effect of oxidative stress at the whole organismal level is well established, and the importance of sirtuins in the molecular underpinnings of oxidative stress is becoming ever clearer ( Merksamer et al, 2013 ; Santos et al, 2016 ; Shahgaldi and Kahmini, 2021 ). In chronic inflammatory disease states, the redox balance shifts to that of oxidative stress, where the normal metabolites of ROS and RNS increase disproportionately ( Sies, 1997 ; Finkel and Holbrook, 2000 ; Jones, 2006 ).…”

Section: Protein Oxidative Post-translational Modificationsmentioning

confidence: 99%

“…Human sirtuins have far too many reported acylated protein substrates to comprehensively cover in this review; thus we focus on a subset of known deacylase substrates involved in metabolism, redox homeostasis, or inflammation ( Table 2 ) as well as those used to show cellular sirtuin inhibition as discussed below. Although the molecular mechanisms negatively regulating sirtuin activity in aging-related pathologies are not fully understood, mounting evidence indicates (patho)physiological reactive oxygen and nitrogen species (ROS and RNS, respectively) play a role ( Merksamer et al, 2013 ; Santos et al, 2016 ; Shahgaldi and Kahmini, 2021 ). ROS/RNS are produced in increasing concentrations with age ( Harman, 1956 ; Finkel and Holbrook, 2000 ) and may negatively regulate sirtuin activity via post-translational modification of critical cysteine and tyrosine side chains.…”

Section: Introduction To Sirtuinsmentioning

confidence: 99%

Sirtuin Oxidative Post-translational Modifications

2021

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Increased sirtuin deacylase activity is correlated with increased lifespan and healthspan in eukaryotes. Conversely, decreased sirtuin deacylase activity is correlated with increased susceptibility to aging-related diseases. However, the mechanisms leading to decreased sirtuin activity during aging are poorly understood. Recent work has shown that oxidative post-translational modification by reactive oxygen (ROS) or nitrogen (RNS) species results in inhibition of sirtuin deacylase activity through cysteine nitrosation, glutathionylation, sulfenylation, and sulfhydration as well as tyrosine nitration. The prevalence of ROS/RNS (e.g., nitric oxide, S-nitrosoglutathione, hydrogen peroxide, oxidized glutathione, and peroxynitrite) is increased during inflammation and as a result of electron transport chain dysfunction. With age, cellular production of ROS/RNS increases; thus, cellular oxidants may serve as a causal link between loss of sirtuin activity and aging-related disease development. Therefore, the prevention of inhibitory oxidative modification may represent a novel means to increase sirtuin activity during aging. In this review, we explore the role of cellular oxidants in inhibiting individual sirtuin human isoform deacylase activity and clarify the relevance of ROS/RNS as regulatory molecules of sirtuin deacylase activity in the context of health and disease.

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A comprehensive review of Sirtuins: With a major focus on redox homeostasis and metabolism

Cited by 52 publications

References 187 publications

Decreased Serum Levels of SIRT1 and SIRT3 Correlate with Severity of Skin and Lung Fibrosis and Peripheral Microvasculopathy in Systemic Sclerosis

Decreased Serum Levels of SIRT1 and SIRT3 Correlate with Severity of Skin and Lung Fibrosis and Peripheral Microvasculopathy in Systemic Sclerosis

Impact of Selenium on Biomarkers and Clinical Aspects Related to Ageing. A Review

Sirtuin Oxidative Post-translational Modifications

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