Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD006613
PROVIDER: PRJNA388462 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic down-regulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/- mice to Ins2+/+ littermate controls, on a genetically stable Ins1-null background. Proteomic and transcriptomic analyses of livers from 25 week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/- mice. Halving Ins2 lowered circulating insulin by 25-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance, and that limiting basal insulin levels can extend lifespan.
2017-07-07 | PXD006613 | Pride
Project description:The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic down-regulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/- mice to Ins2+/+ littermate controls, on a genetically stable Ins1-null background. Proteomic and transcriptomic analyses of livers from 25 week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/- mice. Halving Ins2 lowered circulating insulin by 25-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance, and that limiting basal insulin levels can extend lifespan.
2017-05-31 | GSE99440 | GEO
Project description:Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including yeast, worms, and flies. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction (CR). Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan including increased insulin sensitivity, reduced IGF-1, increased AMPK and PGC-1α activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment (PAGE) revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal and point to new approaches for treating obesity-related disorders and diseases of ageing. Experiment Overall Design: One-year-old male C57BL/6 mice were maintained on AIN-93G standard diet (SD), AIN-93G modified to provide 60% of calories from fat (HC), or HC diet with the addition of 0.04% resveratrol (HCR). Total RNA from the livers of 5 replicate animals from the first 2 groups and 4 from the 3rd group were labeled and hybridized to Agilent 44K whole genome microarrays.
2008-06-21 | E-GEOD-6089 | biostudies-arrayexpress
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: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:Aging and aging-related diseases represent an increasing burden on modern society. Thus, drugs that retard the aging process are highly desirable. Fibroblast growth factor-21 (FGF21) is a hormone secreted by the liver during fasting that elicits diverse aspects of the adaptive starvation response. Among its effects, FGF21 induces hepatic fatty acid oxidation and ketogenesis, increases insulin sensitivity and blocks somatic growth. Here we show that transgenic overexpression of FGF21 markedly extends lifespan in mice without reducing food intake or affecting AMP kinase or mTOR signaling or NAD metabolism. Transcriptomic analysis suggests that FGF21 acts primarily by blunting the growth hormone/insulin-like growth factor-1 signaling pathway in liver. These findings raise the possibility that FGF21 can be used as a hormone therapy to extend lifespan. Liver, epididymal fat and gastrocnemius muscle RNA expression profiles were compared between C57Bl/6J ad libitum, fasted, and calorically restricted mice, as well as between FGF-21 transgenic and their wild-type C57Bl/6J controls.
2012-10-18 | E-GEOD-39313 | 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:Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including yeast, worms, and flies. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction (CR). Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan including increased insulin sensitivity, reduced IGF-1, increased AMPK and PGC-1α activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment (PAGE) revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal and point to new approaches for treating obesity-related disorders and diseases of ageing. Keywords: Drug treatment
2006-11-03 | GSE6089 | GEO
Project description:Long-term consumption of fatty foods is associated with obesity, macrophage activation and inflammation, metabolic imbalance, and a reduced lifespan. We took advantage of Drosophila genetics to investigate the role of macrophages and the pathway(s) that govern their response to dietary stress. Flies fed a lipid-rich diet presented with increased fat storage, systemic JAK-STAT activation, reduced insulin sensitivity and hyperglycaemia, and a shorter lifespan. Drosophila macrophages scavenged lipids and produced the type 1 cytokine upd3, in a scavenger-receptor (croquemort) and JNK-dependent manner. Genetic depletion of macrophages, or macrophage-specific silencing of upd3 decreased JAK-STAT activation and rescued insulin sensitivity and the lifespan of Drosophila, but did not decrease fat storage. NF-M-NM-:B signalling made no contribution to the phenotype observed. These results identify an evolutionarily conserved M-bM-^@M-^Xscavenger receptor-JNK-Type 1 cytokineM-bM-^@M-^Y cassette in macrophages, which controls glucose metabolism and reduces lifespan in Drosophila maintained on a lipid-rich diet via activation of the JAK-STAT pathway Long-term consumption of fatty foods is associated with obesity, macrophage activation and inflammation, metabolic imbalance, and a reduced lifespan. We took advantage of Drosophila genetics to investigate the role of macrophages and the pathway(s) that govern their response to dietary stress. Flies fed a lipid-rich diet presented with increased fat storage, systemic JAK-STAT activation, reduced insulin sensitivity and hyperglycaemia, and a shorter lifespan. Drosophila macrophages scavenged lipids and produced the type 1 cytokine upd3, in a scavenger-receptor (croquemort) and JNK-dependent manner. Genetic depletion of macrophages, or macrophage-specific silencing of upd3 decreased JAK-STAT activation and rescued insulin sensitivity and the lifespan of Drosophila, but did not decrease fat storage. NF-M-NM-:B signalling made no contribution to the phenotype observed. These results identify an evolutionarily conserved M-bM-^@M-^Xscavenger receptor-JNK-Type 1 cytokineM-bM-^@M-^Y cassette in macrophages, which controls glucose metabolism and reduces lifespan in Drosophila maintained on a lipid-rich diet via activation of the JAK-STAT pathway 5 biological samples were FACS-sorted from different batches of Drosophila melanogaster males after 30 days on 15% lipid enriched diet (n=5) and control diet (n=5)
2015-01-30 | E-GEOD-63254 | biostudies-arrayexpress
Project description:To understand how reduced insulin/IGF-1 signaling extends Drosophila lifespan through its downstream transcription factor dFOXO. We conducted ChIP analysis with a dFOXO antibody followed by Illumina high-throughput sequencing from chico heterozygous mutants, which are long-lived and normal sized, and from adult flies with ablated insulin producing cells (IPCs), which are also long-lived. dFOXO bound at promoters of 273 genes common among these genotypes, thus potentially enriching for shared factors in control of aging. Two replicates were sequenced from chico heterozygous mutants and IPC ablated flies.
2013-09-20 | E-GEOD-44686 | biostudies-arrayexpress