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SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases

As an important NAD(+)-dependent enzyme, SIRT6 has received significant attention since its discovery. In view of observations that SIRT6-deficient animals exhibit genomic instability and metabolic disorders and undergo early death, SIRT6 has long been considered a protein of longevity. Recently, gr...

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Detalles Bibliográficos
Autores principales: Guo, Zhenyang, Li, Peng, Ge, Junbo, Li, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: JKL International LLC 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662279/
https://www.ncbi.nlm.nih.gov/pubmed/36465178
http://dx.doi.org/10.14336/AD.2022.0413
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author Guo, Zhenyang
Li, Peng
Ge, Junbo
Li, Hua
author_facet Guo, Zhenyang
Li, Peng
Ge, Junbo
Li, Hua
author_sort Guo, Zhenyang
collection PubMed
description As an important NAD(+)-dependent enzyme, SIRT6 has received significant attention since its discovery. In view of observations that SIRT6-deficient animals exhibit genomic instability and metabolic disorders and undergo early death, SIRT6 has long been considered a protein of longevity. Recently, growing evidence has demonstrated that SIRT6 functions as a deacetylase, mono-ADP-ribosyltransferase and long fatty deacylase and participates in a variety of cellular signaling pathways from DNA damage repair in the early stage to disease progression. In this review, we elaborate on the specific substrates and molecular mechanisms of SIRT6 in various physiological and pathological processes in detail, emphasizing its links to aging (genomic damage, telomere integrity, DNA repair), metabolism (glycolysis, gluconeogenesis, insulin secretion and lipid synthesis, lipolysis, thermogenesis), inflammation and cardiovascular diseases (atherosclerosis, cardiac hypertrophy, heart failure, ischemia-reperfusion injury). In addition, the most recent advances regarding SIRT6 modulators (agonists and inhibitors) as potential therapeutic agents for SIRT6-mediated diseases are reviewed.
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spelling pubmed-96622792022-12-01 SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases Guo, Zhenyang Li, Peng Ge, Junbo Li, Hua Aging Dis Review As an important NAD(+)-dependent enzyme, SIRT6 has received significant attention since its discovery. In view of observations that SIRT6-deficient animals exhibit genomic instability and metabolic disorders and undergo early death, SIRT6 has long been considered a protein of longevity. Recently, growing evidence has demonstrated that SIRT6 functions as a deacetylase, mono-ADP-ribosyltransferase and long fatty deacylase and participates in a variety of cellular signaling pathways from DNA damage repair in the early stage to disease progression. In this review, we elaborate on the specific substrates and molecular mechanisms of SIRT6 in various physiological and pathological processes in detail, emphasizing its links to aging (genomic damage, telomere integrity, DNA repair), metabolism (glycolysis, gluconeogenesis, insulin secretion and lipid synthesis, lipolysis, thermogenesis), inflammation and cardiovascular diseases (atherosclerosis, cardiac hypertrophy, heart failure, ischemia-reperfusion injury). In addition, the most recent advances regarding SIRT6 modulators (agonists and inhibitors) as potential therapeutic agents for SIRT6-mediated diseases are reviewed. JKL International LLC 2022-12-01 /pmc/articles/PMC9662279/ /pubmed/36465178 http://dx.doi.org/10.14336/AD.2022.0413 Text en copyright: © 2022 Guo et al. https://creativecommons.org/licenses/by/2.0/this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Review
Guo, Zhenyang
Li, Peng
Ge, Junbo
Li, Hua
SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases
title SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases
title_full SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases
title_fullStr SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases
title_full_unstemmed SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases
title_short SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases
title_sort sirt6 in aging, metabolism, inflammation and cardiovascular diseases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662279/
https://www.ncbi.nlm.nih.gov/pubmed/36465178
http://dx.doi.org/10.14336/AD.2022.0413
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