SIRT6 serves as a polyhedron in glycolytic metabolism and ageing-related diseases

Yuan, Zhixiao; Zeng, Yutian; Tian, Yao; Wang, Shuai; Hong, Binyan; Yang, Mingyao

doi:10.1016/j.exger.2022.111765

Cited by 4 publications

(3 citation statements)

References 93 publications

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“…Thus, in some studies, HK2 was considered a senescence-related gene. Sirt6 is also involved in glycolytic metabolism [ 46 ]. The present study showed that D-gal reduced TERT expression and increased the levels of ROS, SA- β -galactosidase and HK2.…”

Section: Discussionmentioning

confidence: 99%

“…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 ]. Thus, as a CD38 inhibitor, C3G could alter metabolism and suppress proinflammation via the CD38-Sirt6 pathway, which ultimately contributes to SASP and cell senescence.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…Glycolysis, a key energy production process in almost all mammalian cells, converts glucose into pyruvate. Under aerobic conditions, it enter the mitochondria ( 106 ). When cells are deprived of nutrients or under hypoxia, they undergo anaerobic respiration and convert pyruvate to lactate ( 107 – 109 ).…”

Section: Sirt6 Regulation In Glycolipid Metabolismmentioning

confidence: 99%

SIRT6’s function in controlling the metabolism of lipids and glucose in diabetic nephropathy

Wang,

Liu,

Cai

et al. 2023

Front. Endocrinol.

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Diabetic nephropathy (DN) is a complication of diabetes mellitus (DM) and the main cause of excess mortality in patients with type 2 DM. The pathogenesis and progression of DN are closely associated with disorders of glucose and lipid metabolism. As a member of the sirtuin family, SIRT6 has deacetylation, defatty-acylation, and adenosine diphosphate-ribosylation enzyme activities as well as anti-aging and anticancer activities. SIRT6 plays an important role in glucose and lipid metabolism and signaling, especially in DN. SIRT6 improves glucose and lipid metabolism by controlling glycolysis and gluconeogenesis, affecting insulin secretion and transmission and regulating lipid decomposition, transport, and synthesis. Targeting SIRT6 may provide a new therapeutic strategy for DN by improving glucose and lipid metabolism. This review elaborates on the important role of SIRT6 in glucose and lipid metabolism, discusses the potential of SIRT6 as a therapeutic target to improve glucose and lipid metabolism and alleviate DN occurrence and progression of DN, and describes the prospects for future research.

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