SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases

As an important [NAD.sup.+]-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. Recentl...

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Published inAging and disease Vol. 13; no. 6; pp. 1787 - 1822
Main Authors Guo, Zhenyang, Li, Peng, Ge, Junbo, Li, Hua
Format Journal Article
LanguageEnglish
Published JKL International 01.12.2022
JKL International LLC
Subjects
Aging
Cardiovascular diseases
Development and progression
Genetic aspects
Health aspects
Inflammation
Metabolism
Physiological aspects
Review
Transferases
China
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Summary:As an important [NAD.sup.+]-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. Key words: SIRT6, molecular network, ageing, metabolism, inflammation, cardiovascular diseases
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These authors contributed equally to this work.
ISSN:2152-5250
2152-5250
DOI:10.14336/AD.2022.0413