Restoration of energy homeostasis by SIRT6 extends healthy lifespan

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: May 28, 2021

Aging leads to a gradual decline in physical activity and disrupted energy homeostasis. The NAD+-dependent SIRT6 deacylase regulates aging metabolism through mechanisms that largely remain unknown. Here, we show overexpression reduction frailty lifespan extension both male female B6 mice. A combination of physiological assays, vivo multi-omics analyses 13C lactate tracing identified an age-dependent glucose homeostasis hepatic output wild type In contrast, aged SIRT6-transgenic mice preserve improvement the utilization two major gluconeogenic precursors, glycerol. To mediate these changes, mechanistically, increases gene expression, de novo NAD+ synthesis, systemically enhances glycerol release from adipose tissue. These findings optimizes old age delay healthy aging.

Language: Английский

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Integrated contact lens sensor system based on multifunctional ultrathin MoS2 transistors

Matter, Journal Year: 2020, Volume and Issue: 4(3), P. 969 - 985

Published: Dec. 30, 2020

Language: Английский

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Senolytic drugs, dasatinib and quercetin, attenuate adipose tissue inflammation, and ameliorate metabolic function in old age

Aging Cell, Journal Year: 2023, Volume and Issue: 22(2)

Published: Jan. 13, 2023

Aging results in an elevated burden of senescent cells, senescence-associated secretory phenotype (SASP), and tissue infiltration immune cells contributing to chronic low-grade inflammation a host age-related diseases. Recent evidence suggests that the clearance alleviates its associated dysfunction However, effect this intervention on metabolic function old age remains poorly understood. Here, we demonstrate dasatinib quercetin (D&Q) have senolytic effects, reducing increase β-galactosidase, expression p16 p21 gene P16 protein perigonadal white adipose (pgWAT; all p ≤ 0.04). This treatment also suppressed subset pro-inflammatory SASP genes (mcp1, tnf-α, il-1α, il-1β, il-6, cxcl2, cxcl10), crown-like structures, abundance T macrophages pgWAT (all In liver skeletal muscle, did not find robust D&Q senescence inflammatory markers. Although observe difference glucose tolerance, improved fasting blood (p = 0.001) tolerance 0.007) mice was concomitant with lower hepatic gluconeogenesis. Additionally, insulin-stimulated suppression plasma NEFAs 0.01), reduced fed fasted triglycerides (both 0.04), systemic lipid 0.006). Collectively, from study suggest attenuates improves age. These findings implications for development therapeutic agents combat diseases

Language: Английский

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Bacteroides uniformis combined with fiber amplifies metabolic and immune benefits in obese mice

Gut Microbes, Journal Year: 2021, Volume and Issue: 13(1), P. 1 - 20

Published: Jan. 1, 2021

Gut microbiota represents a therapeutic target for obesity. We hypothesize that B. uniformis CECT 7771 combined with wheat bran extract (WBE), its preferred carbon source, may exert superior anti-obesity effects. performed 17-week intervention in diet-induced obese mice receiving either uniformis, WBE, or their combination to identify interactions and independent actions on metabolism immunity. WBE was the most effective intervention, curbing weight gain adiposity, while exerting more modest effects separately. The restored insulin-dependent metabolic routes fat liver, although bacterium primary driver improving whole-body glucose disposal. Moreover, uniformis-combined caused highest increases butyrate proportion of induced intraepithelial lymphocytes type-3 innate lymphoid cells intestinal epithelium. Thus, strengthening first line immune defense against unhealthy diets associated dysbiosis intestine. This also attenuated altered IL22 signaling liver inflammation. Our study shows opportunities employing aid treatment

Language: Английский

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Microengineered Multi‐Organoid System from hiPSCs to Recapitulate Human Liver‐Islet Axis in Normal and Type 2 Diabetes

Advanced Science, Journal Year: 2021, Volume and Issue: 9(5)

Published: Dec. 23, 2021

Abstract Type 2 diabetes mellitus (T2DM) is a systematic multi‐organ metabolic disease, which characterized by the dynamic interplay among different organs. The increasing incidence of T2DM reflects an urgent need for development in vitro human‐relevant models disease study and drug therapy. Here, new microfluidic multi‐organoid system developed that recapitulates human liver‐pancreatic islet axis normal states. contains two compartmentalized regions connected microchannel network, enabling 3D co‐culture induced pluripotent stem cells (hiPSC)‐derived liver organoids up to 30 days under circulatory perfusion conditions. co‐cultured exhibit favorable growth improved tissue‐specific functions. Transcriptional analyses reveal activation metabolically relevant signaling pathways organoids. Notably, facilitates sensitive glucose‐stimulated insulin secretion from increased glucose utilization tolerance tests. Both display mitochondrial dysfunction decreased transport capacity high conditions, can be alleviated metformin treatment. This novel recapitulate liver‐islet both physiological pathological providing unique platform future research development.

Language: Английский

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