Versatile role of sirtuins in metabolic disorders: From modulation of mitochondrial function to therapeutic interventions

Afzaal, Ammara; Rehman, Kanwal; Kamal, Shagufta; Akash, Muhammad Sajid Hamid

doi:10.1002/jbt.23047

Cited by 29 publications

(19 citation statements)

References 361 publications

(563 reference statements)

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“…1 ) [ 4 ]. Despite the initial recognition that SIRTs primarily play a role in deacetylation, which requires NAD + as a cofactor, a growing body of experiments have demonstrated that SIRTs can also act on many histone and non-histone targets through multiple deacylase and mono-ADP-ribosyltransferase activities, thereby participating in multiple pathophysiological processes, such as cardiovascular diseases, metabolic diseases, autoimmune diseases, infectious diseases, and respiratory diseases [ 4 , 5 , 22 – 28 ]. Notably, each SIRT has specific substrates and exerts distinct effects in respiratory diseases.…”

Section: Overview Of the Sirtuin Familymentioning

confidence: 99%

“…The low selectivity of SIRT modulators has become one of the main obstacles limiting research progress. As the first discovered SIRT1 activator, resveratrol can play a certain role in other SIRTs besides acting on SIRT1 [ 28 ]. Activators may have better selectivity and fewer adverse effects than inhibitors [ 28 ].…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

“…As the first discovered SIRT1 activator, resveratrol can play a certain role in other SIRTs besides acting on SIRT1 [ 28 ]. Activators may have better selectivity and fewer adverse effects than inhibitors [ 28 ]. However, activators, especially specific and selective activators, are rare in number relative to inhibitors.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

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Roles of sirtuins in asthma

Liu

Shi

2022

Respir Res

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Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacylases and deacetylases that participate in a variety of cellular processes, including transcriptional activity, energy metabolism, DNA damage response, inflammation, apoptosis, autophagy, and oxidative stress. As a result, sirtuins are linked to multiple pathophysiological processes, such as cardiovascular diseases, metabolic diseases, autoimmune diseases, infectious diseases, and respiratory diseases. Asthma is the most common respiratory disease, which is characterized by airway inflammation and airway remodeling. Accumulating evidence has indicated that sirtuins are involved in the pathogenesis of asthma. Furthermore, some studies have suggested that sirtuin modulators are potential agents for the treatment of asthma via alteration of the expression or activity of sirtuins. In this review, we illustrate the role of sirtuins in asthma, discuss related molecular mechanisms, and evaluate the sirtuins-targeted therapy for asthma.

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Section: Overview Of the Sirtuin Familymentioning

confidence: 99%

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

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Roles of sirtuins in asthma

Liu

Shi

2022

Respir Res

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“…The metabolic alterations of glucose, lipid, glutamine and NAD+ can facilitate or inhibit cell senescence [ 9 ]. Sirtuins play versatile roles in metabolic disorders from the modulation of mitochondrial function to therapeutic interventions [ 60 ]. Sirt6 serves as a polyhedron in glycolytic metabolism and aging-related diseases [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Sirt6 by CD38 promotes cell senescence and aging

Zhou

Liu

Zhang

et al. 2022

Aging

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Decreased nicotinamide adenine dinucleotide (NAD+) levels accompany aging. CD38 is the main cellular NADase. Cyanidin-3-O-glucoside (C3G), a natural inhibitor of CD38, is a well-known drug that extends the human lifespan. We investigated mechanisms of CD38 in cell senescence and C3G in antiaging. Myocardial H9c2 cells were induced to senescence with D-gal. CD38 siRNA, C3G and UBCS039 (a chemical activator of Sirt6) inhibited D-gal-induced senescence by reducing reactive oxygen species, hexokinase 2 and SA--galactosidase levels. These activators also stimulated cell proliferation and telomerase reverse transcriptase levels, while OSS-128167 (a chemical inhibitor of Sirt6) and Sirt6 siRNA exacerbated the senescent process. H9c2 cells that underwent D-gal-induced cell senescence increased CD38 expression and decreased Sirt6 expression; CD38 siRNA and C3G decreased CD38 expression and increased Sirt6 expression, respectively; and Sirt6 siRNA stimulated cell senescence in the presence of C3G and CD38 siRNA. In D-gal-induced acute aging mice, CD38 and Sirt6 exhibited increased and decreased expression, respectively, in myocardial tissues, and C3G treatment decreased CD38 expression and increased Sirt6 expression in the tissues. C3G also reduced IL-1, IL-6, IL-17A, TNF-α levels and restored NAD+ and NK cell levels in the animals. We suggest that CD38 downregulates Sirt6 expression to promote cell senescence and C3G exerts an antiaging effect through CD38-Sirt6 signaling.

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“…However, the lack of influence on the intensity of apoptosis does not exclude the other beneficial actions of sirtuins in the ischemic brain. In addition, the limitations of the model of photothrombosis used make it suitable for the study of the molecular mechanisms of ischemic damage, rather than the mechanisms of ischemia‒reperfusion damage to the cells, indicate that the neuroprotective action of sirtuins may be important ( Conti et al, 2017 ; Afzaal et al, 2022 ).…”

mentioning

confidence: 99%

Editorial: Sirtuins and brain homeostasis

Szukiewicz

Eubanks²

2022

Front. Physiol.

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Editorial on the Research Topic Sirtuins and brain homeostasisThe homeostatic functions of the human brain include but are not limited to maintaining daily physiological cycles, such as the sleep-wake cycle, controlling appetiteand thirst, regulating energy and glucose metabolism, regulating body temperature and blood pressure, controlling the production and release of hormones, and regulating cognitive processes (Grigorenko et al., 2016;Roh et al., 2016;González-García et al., 2021). Therefore, the preservation of brain homeostasisis crucial for maintaining the state of steady internal, physical, and chemical conditions of a whole organism (Graceli et al., 2020). Epigenetic mechanisms that control gene expression/ activity without changing the DNA sequence play an important role in brain homeostasis. These mechanisms include DNA methylation, histone modifications, nucleosome repositioning, higher-order chromatin remodeling, noncoding RNAs, and RNA and DNA editing (Mehler, 2008;Mansuy and Mohanna, 2011; Petralla et al., 2021). Sirtuins comprise a family of evolutionarily conserved enzymes that perform NAD + -dependent protein deacetylation/acetylation and are involved in the epigenetic machinery (Bosch-Presegué and Vaquero, 2015;Kosciuk et al., 2019). In mammals, seven isoforms of sirtuins (SIRT1-SIRT7) have been identified in different cellular compartments (i.e., nucleus, mitochondria, cytosol), and knowledge about their comprehensive operation is rapidly expanding (Grabowska et al., 2017;Avilkina et al., 2022).This special issue, consisting of original and review papers, has been prepared to showcase thelatest information about the role of sirtuins in the preservation of brain homeostasis in neurological disorders, including neurodegenerative diseases and stroke, and in the context of behavioral responsiveness.A literature review clearly shows that sirtuins regulate various cell functions in the central nervous system (CNS) (Yan et al.). In the mature CNS, this applies to both neurons and glial cells (i.e., astrocytes, oligodendrocytes, and microglial cells). Abnormal levels of sirtuins coexist with CNS disorders, resulting in clinically relevant progressive cognitive impairment and dysfunction of social and physical abilities. Thus, as epigenetic factors, sirtuins participate in processes such as oxidative stress, cell mitigation, apoptosis, and mitochondrial biogenesis, and altered sirtuin

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Versatile role of sirtuins in metabolic disorders: From modulation of mitochondrial function to therapeutic interventions

Cited by 29 publications

References 361 publications

Roles of sirtuins in asthma

Roles of sirtuins in asthma

Downregulation of Sirt6 by CD38 promotes cell senescence and aging

Editorial: Sirtuins and brain homeostasis

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