Mus musculus
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PROVIDER: PRJNA120447 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet
| PRJNA219481 | ENA
Project description:Activation of Sirt1, the mammalian homolog of an NAD+-dependent deacetylase known to modulate lifespan in lower organisms, is thought to hold promise as a strategy for delaying aging in mammals. SRT1720, a novel compound developed as a specific and potent activator of Sirt1, has shown promising effects to glucose homeostasis in short-term studies of rats and mice. Here we show SRT1720 extends both mean and maximum lifespan of mice fed a high-fat diet and has concrete benefits to health including reduced liver steatosis and increased insulin sensitivity and locomotor activity. Gene expression profiles and markers of inflammation and apoptosis were also restored to levels more reflective of standard diet controls. Furthermore, the benefits incurred by SRT1720 occurred in the absence of any observable toxicity. The current findings provide hope that safe and effective treatments may be developed to mitigate age-related diseases and enhance lifespan in humans. Male C57BL/6J mice obtained at 12 weeks of age were maintained on a standard purified mouse diet (AIN-93G) until 56 weeks of age prior to the start of the experiment. Beginning at 56 weeks of age, the SD group was fed a standard AIN-93G diet for the duration of the study. Three separate groups were placed on a high-fat diet (HFD) (AIN-93G modified by the addition of hydrogenated coconut oil to provide 60% of calories from fat) or HFD + 30mg/kg body weight SRT1720 (HFD-L) or 100mg/kg body weight SRT1720 (HFD-H) and remained on those diets throughout the study. All mice were fed ad libitum. Food intake and body weight were measured biweekly for the duration of the study.
2011-08-17 | E-GEOD-19102 | biostudies-arrayexpress
Project description:Activation of Sirt1, the mammalian homolog of an NAD+-dependent deacetylase known to modulate lifespan in lower organisms, is thought to hold promise as a strategy for delaying aging in mammals. SRT1720, a novel compound developed as a specific and potent activator of Sirt1, has shown promising effects to glucose homeostasis in short-term studies of rats and mice. Here we show SRT1720 extends both mean and maximum lifespan of mice fed a high-fat diet and has concrete benefits to health including reduced liver steatosis and increased insulin sensitivity and locomotor activity. Gene expression profiles and markers of inflammation and apoptosis were also restored to levels more reflective of standard diet controls. Furthermore, the benefits incurred by SRT1720 occurred in the absence of any observable toxicity. The current findings provide hope that safe and effective treatments may be developed to mitigate age-related diseases and enhance lifespan in humans.
2011-08-18 | GSE19102 | GEO
Project description:The prevention or delay of the onset of age-related diseases prolongs survival and improves quality of life while reducing the burden on the health care system. Activation of sirtuin 1 (SIRT1), an NAD+ deacetylase, improves metabolism and confers protection against physiological and cognitive disturbances in old age. SRT1720 is a specific SIRT1 activator that has health and lifespan benefits in adult mice fed a highfat diet. We found extension in lifespan, delayed onset of age-related metabolic diseases, and improved general health in mice fed a standard diet after SRT1720 supplementation. Inhibition of pro-inflammatory gene expression both in the liver and muscle of SRT1720-treated animals was noted. SRT1720 lowered phosphorylation of NF-κB pathway regulators in vitro only when SIRT1 was functionally present. Combined with our previous work, the current study further supports the beneficial effects of SRT1720 on health across the lifespan in mice.
2014-12-20 | GSE50987 | GEO
Project description:Increased expression of SIRT1 extends the lifespan of lower organisms and delays the onset of age-related diseases in mammals. Here, we show that SRT2104, a synthetic small molecule activator of SIRT1, extends both mean and maximal lifespan of mice fed a standard diet. This is accompanied by improvements in health, including enhanced motor coordination, performance, bone mineral density and insulin sensitivity associated with higher mitochondrial content and decreased inflammation. Short-term SRT2104 treatment preserves bone and muscle mass in an experimental model of atrophy. These results demonstrate it is possible to design a small molecule that can slow aging and delay multiple age-related diseases in mammals, supporting the therapeutic potential of SIRT1 activators in humans. Key words: Sirtuins, lifespan, healthspan, osteoporosis, muscle wasting, inflammation
2014-09-22 | GSE49000 | GEO
Project description:Recovering matrikine-induced immune dysfunction extends health- and lifespan (PRJCA025375)
| PRJDB38369 | ENA
Project description:Reversible and sub-lethal stresses to the mitochondria elicit a program of compensatory responses that ultimately improve mitochondrial function, a conserved anti-aging mechanism termed mitohormesis. Here, we show that harmol, a member of the beta-carbolines family with anti-depressant properties, improves mitochondrial function and metabolic parameters, and extends healthspan. Treatment with harmol induces a transient mitochondrial depolarization, a strong mitophagy response, and the AMPK compensatory pathway both in cultured C2C12 myotubes and in male mouse liver, brown adipose tissue and muscle, even though harmol crosses poorly the blood-brain barrier. Mechanistically, simultaneous modulation of the targets of harmol monoamine-oxidase B and GABA-A receptor reproduces harmol-induced mitochondrial improvements. Diet-induced pre-diabetic male mice improve their glucose tolerance, liver steatosis and insulin sensitivity after treatment with harmol. Harmol or a combination of monoamine oxidase B and GABA-A receptor modulators extend the lifespan of hermaphrodite Caenorhabditis elegans or female Drosophila melanogaster. Finally, two-year-old male and female mice treated with harmol exhibit delayed frailty onset with improved glycemia, exercise performance and strength. Our results reveal that peripheral targeting of monoamine oxidase B and GABA-A receptor, common antidepressant targets, extends healthspan through mitohormesis.
2023-05-26 | MTBLS7533 | MetaboLights
Project description:Caloric restriction extends lifespan and healthspan across species, with feeding times synchronized to circadian rhythms further maximizing its benefits. However, the mechanisms linking diet, diurnal rhythms, and lifespan are not fully understood. In mice, the time point most strongly tied to dietary effects on lifespan coincides with the peak of glucocorticoid secretion (ZT12, lights-off). Caloric restriction raises circulating glucocorticoid hormone levels, but their functional relevance remains untested. We show that the glucocorticoid receptor (GR) is critical for the effects of caloric restriction. Hepatocyte-specific GR mutant mice fail to respond to caloric restriction indicating that increased glucocorticoid amplitudes support its benefits. Using multiomics techniques in murine liver, we find that nutrient deprivation elicits a nuclear switch from active STAT signaling to increased FOXO1 activity, enabling the GR to activate a unique diet-specific gene expression program. Taken together, our results suggest that glucocorticoid rhythms are crucial for caloric restriction-induced metabolic reprogramming.
2025-11-04 | GSE298149 | GEO
Project description:Caloric restriction extends lifespan and healthspan across species, with feeding times synchronized to circadian rhythms further maximizing its benefits. However, the mechanisms linking diet, diurnal rhythms, and lifespan are not fully understood. In mice, the time point most strongly tied to dietary effects on lifespan coincides with the peak of glucocorticoid secretion (ZT12, lights-off). Caloric restriction raises circulating glucocorticoid hormone levels, but their functional relevance remains untested. We show that the glucocorticoid receptor (GR) is critical for the effects of caloric restriction. Hepatocyte-specific GR mutant mice fail to respond to caloric restriction indicating that increased glucocorticoid amplitudes support its benefits. Using multiomics techniques in murine liver, we find that nutrient deprivation elicits a nuclear switch from active STAT signaling to increased FOXO1 activity, enabling the GR to activate a unique diet-specific gene expression program. Taken together, our results suggest that glucocorticoid rhythms are crucial for caloric restriction-induced metabolic reprogramming.
2025-11-04 | GSE248866 | GEO
Project description:Toll-like receptor 5 (TLR5) plays a critical role beyond its traditional function in innate immunity, significantly impacting metabolic regulation and liver health. Previously, we reported that TLR5 activation extends healthspan and lifespan in aging mice. This study demonstrates that TLR5 deficiency leads to pronounced metabolic abnormalities with age, primarily affecting liver metabolic functions rather than intestinal inflammation. Comprehensive RNA sequencing analysis revealed that TLR5 deficiency induces gene expression changes in liver tissue similar to those caused by the methionine-choline deficient (MCD) diet, particularly affecting lipid metabolism and circadian rhythm-related genes. TLR5 KO mice displayed an increased propensity for liver fibrosis and lipid accumulation under the MCD diet, exacerbating liver pathology. Both hepatocytes and hepatic stellate cells in TLR5 KO mice were functionally impacted, leading to metabolic dysfunction and fibrosis. These findings suggest that TLR5 could be a significant target for addressing metabolic diseases that arise and worsen with aging. Furthermore, understanding the mechanisms by which TLR5 activation extends healthspan could provide valuable insights into therapeutic strategies for enhancing longevity and managing age-related metabolic disorders.
2025-06-18 | GSE272622 | GEO