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Sirtuins in Health and Disease
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Sirtuins in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 40223

Special Issue Editors

Dr. Heiko Bugger

E-Mail Website
Guest Editor
Division of Cardiology, Medical University of Graz, Graz, Austria
Interests: cardiovascular disease; heart failure; diabetes; cardiac energy metabolism
Dr. Simon Sedej

E-Mail Website
Guest Editor
1. Division of Cardiology, Medical University of Graz, Graz, Austria
2. BioTechMed Graz, Graz, Austria
Interests: caloric restriction mimetics; autophagy; myocardial remodeling, heart failure; aging; metabolic syndrome

Special Issue Information

Dear Colleagues,

The discovery and characterization of sirtuins as NAD+-dependent deacylases have revolutionized our understanding of post-translational protein regulation. In fact, numerous post-translational modifications have been attributed to the activity of different sirtuins with distinct cellular localization, and recent findings have advanced our knowledge of the importance of sirtuin-catalyzed posttranslational modifications in health and disease. Sirtuins have been identified as major regulators of a variety of fundamental intracellular pathways and, thus, play a critical role in aging, energy metabolism, and in the adaptation to cellular stressors. That said, sirtuins have been implicated in the pathology of age-related maladies, including cancer, diabetes, and neurodegenerative or cardiovascular diseases, mostly mediating protective effects upon activation. Of note, clinical trials have been initiated to evaluate the therapeutic potential of sirtuin activation.

This Special Issue in the International Journal of Molecular Sciences aims at presenting contemporary research on the role of sirtuins both in health and disease, which shall include research in different organisms and models, and can spread across the entirety of cellular physiology and organ disease. We cordially invite you to submit original articles, review articles, methodological papers, as well as studies related to clinical cases. We encourage researchers to address the current knowledge as well as existing controversies, or present outstanding questions and new concepts related to sirtuins and NAD+ metabolism.

Dr. Heiko Bugger
Dr. Simon Sedej
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Caloric restriction
  • Aging
  • NAD+ metabolism
  • Sirtuin
  • Acetylation
  • Metabolic disease
  • Longevity
  • Posttranslational modification

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Published Papers (7 papers)

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Editorial

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2 pages, 172 KiB  
Editorial
Editorial of Special Issue “Sirtuins in Health and Disease”
by Simon Sedej and Heiko Bugger
Int. J. Mol. Sci. 2021, 22(10), 5054; https://doi.org/10.3390/ijms22105054 - 11 May 2021
Viewed by 1734
Abstract
The discovery and characterization of sirtuins as NAD+-dependent deacylases have transformed our understanding of post-translational protein regulation [...] Full article
(This article belongs to the Special Issue Sirtuins in Health and Disease)

Research

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16 pages, 2895 KiB  
Article
Decreased Urinary Levels of SIRT1 as Non-Invasive Biomarker of Early Renal Damage in Hypertension
by Olga Martinez-Arroyo, Ana Ortega, Miriam Galera, Elena Solaz, Sergio Martinez-Hervas, Josep Redon and Raquel Cortes
Int. J. Mol. Sci. 2020, 21(17), 6390; https://doi.org/10.3390/ijms21176390 - 2 Sep 2020
Cited by 13 | Viewed by 2554
Abstract
Sirtuins have become important players in renal damage in hypertension and diabetes, but their value as biomarkers is poorly assessed. The aims of the study were to evaluate the levels of sirtuin1 (SIRT1), and two miRNAs that regulate SIRT1 expression in hypertensive patients [...] Read more.
Sirtuins have become important players in renal damage in hypertension and diabetes, but their value as biomarkers is poorly assessed. The aims of the study were to evaluate the levels of sirtuin1 (SIRT1), and two miRNAs that regulate SIRT1 expression in hypertensive patients with incipient renal damage with and without diabetes. We quantified urinary SIRT1 and claudin 1 (CLDN1) mRNA and miR34-a and miR-200a levels by quantitative real-time polymerase chain reaction (RT-qPCR) from patients and in cultured podocytes treated with high glucose and angiotensin II. Western blot and fluorescence analyses were also performed. We found decreased SIRT1 levels in patients with increased urinary albumin excretion (UAE), the lowest with diabetes presence, and a strong association with UAE, discriminating incipient renal damage. In vitro experiments also showed SIRT1 overall decreases in podocyte cultures under treatment conditions. In urine samples, miR-34a was reduced and miR-200a increased, both related to UAE levels. However, both miRNAs were generally increased in podocyte cultures under high glucose and angiotensin-II treatment. These results show a significant urinary SIRT1 decrease in albuminuric hypertensive patients, strongly associated with albuminuria, suggesting that SIRT1 could be a potential and non-invasive method to assess incipient renal damage in hypertensive patients. Full article
(This article belongs to the Special Issue Sirtuins in Health and Disease)
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Review

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20 pages, 1919 KiB  
Review
A Molecular Perspective on Sirtuin Activity
by Carla S. S. Teixeira, Nuno M. F. S. A. Cerqueira, Pedro Gomes and Sérgio F. Sousa
Int. J. Mol. Sci. 2020, 21(22), 8609; https://doi.org/10.3390/ijms21228609 - 15 Nov 2020
Cited by 36 | Viewed by 5330
Abstract
The protein acetylation of either the α-amino groups of amino-terminal residues or of internal lysine or cysteine residues is one of the major posttranslational protein modifications that occur in the cell with repercussions at the protein as well as at the metabolome level. [...] Read more.
The protein acetylation of either the α-amino groups of amino-terminal residues or of internal lysine or cysteine residues is one of the major posttranslational protein modifications that occur in the cell with repercussions at the protein as well as at the metabolome level. The lysine acetylation status is determined by the opposing activities of lysine acetyltransferases (KATs) and lysine deacetylases (KDACs), which add and remove acetyl groups from proteins, respectively. A special group of KDACs, named sirtuins, that require NAD+ as a substrate have received particular attention in recent years. They play critical roles in metabolism, and their abnormal activity has been implicated in several diseases. Conversely, the modulation of their activity has been associated with protection from age-related cardiovascular and metabolic diseases and with increased longevity. The benefits of either activating or inhibiting these enzymes have turned sirtuins into attractive therapeutic targets, and considerable effort has been directed toward developing specific sirtuin modulators. This review summarizes the protein acylation/deacylation processes with a special focus on the current developments in the sirtuin research field. Full article
(This article belongs to the Special Issue Sirtuins in Health and Disease)
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21 pages, 854 KiB  
Review
The Role of Sirtuins in Kidney Diseases
by Yu Ah Hong, Ji Eun Kim, Minjee Jo and Gang-Jee Ko
Int. J. Mol. Sci. 2020, 21(18), 6686; https://doi.org/10.3390/ijms21186686 - 12 Sep 2020
Cited by 43 | Viewed by 4877
Abstract
Sirtuins (SIRTs) are class III histone deacetylases (HDACs) that play important roles in aging and a wide range of cellular functions. Sirtuins are crucial to numerous biological processes, including proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammals have seven different sirtuins, [...] Read more.
Sirtuins (SIRTs) are class III histone deacetylases (HDACs) that play important roles in aging and a wide range of cellular functions. Sirtuins are crucial to numerous biological processes, including proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammals have seven different sirtuins, SIRT1–7, and the diverse biological functions of each sirtuin are due to differences in subcellular localization, expression profiles, and cellular substrates. In this review, we summarize research advances into the role of sirtuins in the pathogenesis of various kidney diseases including acute kidney injury, diabetic kidney disease, renal fibrosis, and kidney aging along with the possible underlying molecular mechanisms. The available evidence indicates that sirtuins have great potential as novel therapeutic targets for the prevention and treatment of kidney diseases. Full article
(This article belongs to the Special Issue Sirtuins in Health and Disease)
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18 pages, 1287 KiB  
Review
Roles of Mitochondrial Sirtuins in Mitochondrial Function, Redox Homeostasis, Insulin Resistance and Type 2 Diabetes
by Chih-Hao Wang and Yau-Huei Wei
Int. J. Mol. Sci. 2020, 21(15), 5266; https://doi.org/10.3390/ijms21155266 - 24 Jul 2020
Cited by 58 | Viewed by 6315
Abstract
Mitochondria are the metabolic hubs that process a number of reactions including tricarboxylic acid cycle, β-oxidation of fatty acids and part of the urea cycle and pyrimidine nucleotide biosynthesis. Mitochondrial dysfunction impairs redox homeostasis and metabolic adaptation, leading to aging and metabolic disorders [...] Read more.
Mitochondria are the metabolic hubs that process a number of reactions including tricarboxylic acid cycle, β-oxidation of fatty acids and part of the urea cycle and pyrimidine nucleotide biosynthesis. Mitochondrial dysfunction impairs redox homeostasis and metabolic adaptation, leading to aging and metabolic disorders like insulin resistance and type 2 diabetes. SIRT3, SIRT4 and SIRT5 belong to the sirtuin family proteins and are located at mitochondria and also known as mitochondrial sirtuins. They catalyze NAD+-dependent deacylation (deacetylation, demalonylation and desuccinylation) and ADP-ribosylation and modulate the function of mitochondrial targets to regulate the metabolic status in mammalian cells. Emerging evidence has revealed that mitochondrial sirtuins coordinate the regulation of gene expression and activities of a wide spectrum of enzymes to orchestrate oxidative metabolism and stress responses. Mitochondrial sirtuins act in synergistic or antagonistic manners to promote respiratory function, antioxidant defense, insulin response and adipogenesis to protect individuals from aging and aging-related metabolic abnormalities. In this review, we focus on the molecular mechanisms by which mitochondrial sirtuins regulate oxidative metabolism and antioxidant defense and discuss the roles of their deficiency in the impairment of mitochondrial function and pathogenesis of insulin resistance and type 2 diabetes. Full article
(This article belongs to the Special Issue Sirtuins in Health and Disease)
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24 pages, 941 KiB  
Review
Relevance of SIRT1-NF-κB Axis as Therapeutic Target to Ameliorate Inflammation in Liver Disease
by Estefanía de Gregorio, Anna Colell, Albert Morales and Montserrat Marí
Int. J. Mol. Sci. 2020, 21(11), 3858; https://doi.org/10.3390/ijms21113858 - 29 May 2020
Cited by 131 | Viewed by 12816
Abstract
Inflammation is an adaptive response in pursuit of homeostasis reestablishment triggered by harmful conditions or stimuli, such as an infection or tissue damage. Liver diseases cause approximately 2 million deaths per year worldwide and hepatic inflammation is a common factor to all of [...] Read more.
Inflammation is an adaptive response in pursuit of homeostasis reestablishment triggered by harmful conditions or stimuli, such as an infection or tissue damage. Liver diseases cause approximately 2 million deaths per year worldwide and hepatic inflammation is a common factor to all of them, being the main driver of hepatic tissue damage and causing progression from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH), cirrhosis and, ultimately, hepatocellular carcinoma (HCC). The metabolic sensor SIRT1, a class III histone deacetylase with strong expression in metabolic tissues such as the liver, and transcription factor NF-κB, a master regulator of inflammatory response, show an antagonistic relationship in controlling inflammation. For this reason, SIRT1 targeting is emerging as a potential strategy to improve different metabolic and/or inflammatory pathologies. In this review, we explore diverse upstream regulators and some natural/synthetic activators of SIRT1 as possible therapeutic treatment for liver diseases. Full article
(This article belongs to the Special Issue Sirtuins in Health and Disease)
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16 pages, 703 KiB  
Review
Sirtuins and SIRT6 in Carcinogenesis and in Diet
by Maria de Céu Teixeira, Elena Sanchez-Lopez, Marta Espina, Maria Luisa Garcia, Alessandra Durazzo, Massimo Lucarini, Ettore Novellino, Selma B. Souto, Antonello Santini and Eliana B. Souto
Int. J. Mol. Sci. 2019, 20(19), 4945; https://doi.org/10.3390/ijms20194945 - 7 Oct 2019
Cited by 21 | Viewed by 5686
Abstract
Sirtuins are a highly conserved family of nicotinamide adenine dinucleotide (NAD)-dependent protein lysine modifying enzymes. They are key regulators for a wide variety of cellular and physiological processes such as cell proliferation, differentiation, DNA damage and stress response, genome stability, cell survival, metabolism, [...] Read more.
Sirtuins are a highly conserved family of nicotinamide adenine dinucleotide (NAD)-dependent protein lysine modifying enzymes. They are key regulators for a wide variety of cellular and physiological processes such as cell proliferation, differentiation, DNA damage and stress response, genome stability, cell survival, metabolism, energy homeostasis, organ development and aging. Aging is one of the major risk factors of cancer, as many of the physiological mechanisms and pathologies associated with the aging process also contribute to tumor initiation, growth and/or metastasis. This review focuses on one the mammalian sirtuins, SIRT6, which has emerged as an important regulator of longevity and appears to have multiple biochemical functions that interfere with tumor development and may be useful in cancer prevention and for site-specific treatment. The recent evidence of the role of SIRT6 in carcinogenesis is also discussed, focusing on the potential use of SIRT6 modulators in cancer nanomedicine. Full article
(This article belongs to the Special Issue Sirtuins in Health and Disease)
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