ArticleAging cell2020
A high-fat diet reverses metabolic disorders and premature aging by modulating insulin and IGF1 signaling in SIRT6 knockout mice.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Hepatic SIRT6 Deficiency Accelerates Female-Specific Aging Through SULT1E1-Mediated Estrogen Depletion.International journal of molecular sciences · 2026Article
- SIRT6 overexpression counteracts chromatin aging in the male murine liver.Nature communications · 2026Article
- Histone deacetylase SIRT6 regulates tryptophan catabolism and prevents metabolite imbalance associated with neurodegeneration.Nature communications · 2025Article
- Adipocyte Hyperplasia Facilitated Adipose Tissue Expansion to Alleviate Hepatopancreas Injury in Nile Tilapia (Aquaculture nutrition · 2025Article
- NAD metabolism: Role in senescence regulation and aging.Aging cell · 2024Review
- Effects of dietary genistin supplementation on reproductive performance, immunity and antioxidative capacity in gestating sows.Frontiers in veterinary science · 2024Article
- Pachymic acid modulates sirtuin 6 activity to alleviate lipid metabolism disorders.Experimental and therapeutic medicine · 2023Article
- SAPS3 subunit of protein phosphatase 6 is an AMPK inhibitor and controls metabolic homeostasis upon dietary challenge in male mice.Nature communications · 2023Article
- Decreased Enterobacteriaceae translocation due to gut microbiota remodeling mediates the alleviation of premature aging by a high-fat diet.Aging cell · 2023Article
- Identification of lactate regulation pattern on tumor immune infiltration, therapy response, and DNA methylation in diffuse large B-cell lymphoma.Frontiers in immunology · 2023Article
- The many faces of SIRT6 in the retina and retinal pigment epithelium.Frontiers in cell and developmental biology · 2023Review
- Nutrition Strategies Promoting Healthy Aging: From Improvement of Cardiovascular and Brain Health to Prevention of Age-Associated Diseases.Nutrients · 2022Review
- Tartary Buckwheat (Foods (Basel, Switzerland) · 2022Article
- Ample dietary fat reduced the risk of primary vesical calculi by inducing macrophages to engulf budding crystals in mice.Acta pharmaceutica Sinica. B · 2022Article
- Roles of SIRT6 in kidney disease: a novel therapeutic target.Cellular and molecular life sciences : CMLS · 2021Article
- Supplementing daidzein in diets improves the reproductive performance, endocrine hormones and antioxidant capacity of multiparous sows.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2021Article
- Are fat and sugar just as detrimental in old age?GeroScience · 2021Review
- A Comprehensive Analysis into the Therapeutic Application of Natural Products as SIRT6 Modulators in Alzheimer's Disease, Aging, Cancer, Inflammation, and Diabetes.International journal of molecular sciences · 2021Review
- SPATA4 improves aging-induced metabolic dysfunction through promotion of preadipocyte differentiation and adipose tissue expansion.Aging cell · 2021Article
- A high-fat diet reverses metabolic disorders and premature aging by modulating insulin and IGF1 signaling in SIRT6 knockout mice.Aging cell · 2020Article
Corrections and comments
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Authors and funding
9 authors.
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Abstract
Mammalian sirtuin 6 (SIRT6) is involved in the regulation of many essential processes, especially metabolic homeostasis. SIRT6 knockout mice undergo premature aging and die at age ~4 weeks. Severe glycometabolic disorders have been found in SIRT6 knockout mice, and whether a dietary intervention can rescue SIRT6 knockout mice remains unknown. In our study, we found that at the same calorie intake, a high-fat diet dramatically increased the lifespan of SIRT6 knockout mice to 26 weeks (males) and 37 weeks (females), reversed multi-organ atrophy, and reduced body weight, hypoglycemia, and premature aging. Furthermore, the high-fat diet partially but significantly normalized the global gene expression profile in SIRT6 knockout mice. Regarding the mechanism, excessive glucose uptake and glycolysis induced by the SIRT6 deficiency were attenuated in skeletal muscle through inhibition of insulin and IGF1 signaling by the high-fat diet. Similarly, fatty acids but not ketone bodies inhibited glucose uptake, glycolysis, and senescence in SIRT6 knockout fibroblasts, whereas PI3K inhibition antagonized the effects of a high-fatty-acid medium in vitro. Overall, the high-fat diet dramatically reverses numerous consequences of SIRT6 deficiency through modulation of insulin and IGF1 signaling, providing a new basis for elucidation of SIRT6 and fatty-acid functions and supporting novel therapeutic approaches against metabolic disorders and aging-related diseases.
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