Caenorhabditis elegans strain:N2 and eat-2
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA422473 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Drug synergy slows ageing and improves healthspan through IGF and SREBP lipid signaling
| PRJNA423001 | ENA
Project description:Pharmacological interventions directly modulating ageing would extend human healthspan, resulting in dramatic medical and economic benefits. Such interventions should be efficacious in adults and ideally repurpose drugs known to be safe. Here we show that dramatic lifespan extension can be achieved by targeting multiple, evolutionarily conserved ageing pathways using drugs already used in humans. Using this approach in C. elegans, we were able to slow ageing, improve healthspan and minimize trade-offs. We show that daf-2, daf-7 and sbp-1 (mammalian SREBP-1c) interact upstream of changes in lipid metabolism, resulting in increased monounsaturated fatty acid content and lifespan extension. For one combination, we observed evolutionary conservation in fruit flies. To the best of our knowledge, this is the largest lifespan effect ever reported for any adult-onset drug treatment in C. elegans. Drug repurposing approaches, by leveraging drugs already approved for humans, could lead to rapid translation of experimental results to clinical applications.
2018-12-17 | GSE108263 | GEO
Project description:This study explored the role of the growth hormone (GH) / insulin-like growth factor 1 (IGF-1) axis on the life-long caloric restriction (CR)-associated remodeling of white adipose tissue (WAT). Adipocyte size and gene expression profiles, using high-density oligonucleotide microarrays, were analyzed in WAT of six- to seven-month old wild Wistar rats fed ad libitum (AL) or subjected to a 30% caloric restriction (CR), and heterozygous transgenic dwarf rats bearing an anti-sense GH transgene fed ad libitum (Tg). While not significant in Tg rats, adipocyte size was significantly reduced in CR rats compared with AL rats. The microarray data based on the principal component analysis demonstrated that the gene expression profile of CR rats markedly differed from the AL rats, while Tg hardly differed, suggesting that CR-associated WAT remodeling was predominantly regulated in a GH/IGF-1-independent manner. The gene cluster with the largest change induced by CR included several genes involved in lipid biosynthesis and inflammation. Moreover, many of the genes transcriptionally regulated by sterol regulatory element binding proteins (SREBPs) were found in the cluster related to lipid biosynthesis. Real-time reverse transcription polymerase chain reaction analysis confirmed that the expression of SREBP-1 and its down-stream targets was particularly up-regulated in CR rats compared with SREBP-2 and its down-stream targets. Our findings suggest that SREBP-1 is a major transcription factor in CR-associated remodeling of WAT, and might be one of the key regulators of the anti-aging and pro-longevity effects of CR. The three groups: GH antisense, caloric restriction, and the control were compared by using PCA.
2012-09-27 | E-GEOD-30668 | biostudies-arrayexpress
Project description:Dietary intervention constitutes a feasible approach for modulating metabolism and improving healthspan and lifespan. Methionine restriction (MR) delays the appearance of age-related diseases and increases longevity in normal mice. However, the effect of MR on premature aging remains to be elucidated. Here, we describe that MR extends lifespan in two different mouse models of Hutchinson-Gilford progeria syndrome (HGPS) by reversing the transcriptome alterations in inflammation and DNA-damage response genes present in this condition. Further, MR improves the lipid profile and alters the levels of bile acids, both in wild-type and in progeroid mice. Notably, treatment with the bile acid cholic acid improves healthspan and lifespan in vivo. These results suggest the existence of a metabolic pathway involved in the longevity extension achieved by MR and support the possibility of dietary interventions for treating progeria.
2018-08-27 | GSE117188 | GEO
Project description:Sterol regulatory element binding proteins (SREBPs) are key transcriptional regulators of lipid metabolism. To define functional differences between the three mammalian SREBPs we are using genome-wide ChIP-seq with isoform-specific antibodies and chromatin from select tissues of mice challenged with different dietary conditions that enrich for specific SREBPs. We show hepatic SREBP-2 binds preferentially to two different gene-proximal motifs. Gene ontology analyses suggests SREBP-2 targets lipid metabolic processes as expected but apoptosis and autophagy gene categories were also enriched. We show SREBP-2 directly activates autophagy genes during cell sterol depletion, conditions known to induce both autophagy and nuclear SREBP-2 levels. Additionally, SREBP-2 knockdown during nutrient depletion decreased autophagosome formation and lipid droplet association of the autophagosome targeting protein LC3. Thus, the lipid droplet could be viewed as a third source of cellular cholesterol, which along with sterol synthesis and uptake, is also regulated by SREBP-2. Examination of hepatic SREBP-2 binding using ChIP-Seq. One ChIP-Seq dataset and one IgG control.
2011-03-22 | E-GEOD-28082 | biostudies-arrayexpress
Project description:This study explored the role of the growth hormone (GH) / insulin-like growth factor 1 (IGF-1) axis on the life-long caloric restriction (CR)-associated remodeling of white adipose tissue (WAT). Adipocyte size and gene expression profiles, using high-density oligonucleotide microarrays, were analyzed in WAT of six- to seven-month old wild Wistar rats fed ad libitum (AL) or subjected to a 30% caloric restriction (CR), and heterozygous transgenic dwarf rats bearing an anti-sense GH transgene fed ad libitum (Tg). While not significant in Tg rats, adipocyte size was significantly reduced in CR rats compared with AL rats. The microarray data based on the principal component analysis demonstrated that the gene expression profile of CR rats markedly differed from the AL rats, while Tg hardly differed, suggesting that CR-associated WAT remodeling was predominantly regulated in a GH/IGF-1-independent manner. The gene cluster with the largest change induced by CR included several genes involved in lipid biosynthesis and inflammation. Moreover, many of the genes transcriptionally regulated by sterol regulatory element binding proteins (SREBPs) were found in the cluster related to lipid biosynthesis. Real-time reverse transcription polymerase chain reaction analysis confirmed that the expression of SREBP-1 and its down-stream targets was particularly up-regulated in CR rats compared with SREBP-2 and its down-stream targets. Our findings suggest that SREBP-1 is a major transcription factor in CR-associated remodeling of WAT, and might be one of the key regulators of the anti-aging and pro-longevity effects of CR.
2012-09-27 | GSE30668 | GEO
Project description:There is accumulating evidence that interfering with the basic aging mechanisms can enhance healthy longevity. Many cellular processes contribute to aging and are referred to as “hallmarks of aging”; by presumption, interventional/therapeutic strategies targeting on multiple ageing hallmarks could be more effective to delay ageing than targeting on one hallmark. While the health-promoting qualities of marine oils have been extensively studied, the underlying molecular mechanisms are not fully understood. Lipid extracts from Antarctic krill are rich in long-chain omega-3 fatty acids (eicosapentaenoic acid/EPA and docosahexaenoic acid/DHA), choline, and astaxanthin. Here, we investigated whether krill oil promotes healthy aging in the small roundworm C. elegans. We show that krill oil rewires distinct gene expression programs that contribute to attenuate several aging hallmarks, including oxidative stress, proteotoxic stress, senescence, genomic instability, and mitochondrial dysfunction. In a C. elegans model of Parkinson´s disease, krill oil protects dopaminergic neurons from aging-related degeneration, decreases alpha synuclein aggregation, and improves dopamine-dependent behavior and cognition. Mechanistically, krill oil increases neuronal resilience through temporal transcriptome rewiring to promote anti-oxidative stress and inflammation via healthspan regulating transcription factors such as SNK-1. However, also krill oil promotes DA neuron survival through regulation of synaptic transmission and neuronal functions via PBO-2 and RIM-1. Collectively, krill oil rewires global gene expression programs and promotes healthy aging via abrogating multiple ageing hallmarks, shedding light on further pre-clinical and clinical explorations.
2022-11-30 | GSE207152 | GEO
Project description:Caloric restriction (CR) slows the ageing process in many orgamisms, including mice. Liver is an important metabolic organ with active RNA expression. CR reprogrammes hepatic metabolism as well as hepatic transcriptome. We sought to study CR-induced transcriptomic changes in mouse liver to investigate the anti-ageing mechanisms of CR.
2018-01-18 | GSE93747 | GEO
Project description:The key lipid metabolism transcription factor sterol regulatory element-binding protein (SREBP)-1a integrates gene regulatory effects of hormones, cytokines, nutrition and metabolites as lipids, glucose or cholesterol via stimuli specific phosphorylation by different MAPK cascades. We have formerly reported the systemic impact of phosphorylation in transgenic mouse models with liver-specific overexpression of the N-terminal transcriptional active domain of SREBP-1a (alb-SREBP-1a) or a MAPK kinase phosphorylation sites deficient variant (alb-SREBP-1a∆P; (S63A, S117A, T426V)), respectively. Here we investigated the molecular basis of the systemic observation in holistic hepatic gene expression analyses and lipid degrading organelles involved in the pathogenesis of metabolic syndrome, i.e. peroxisomes, by 2D-DIGE and mass spectrometry analyses. Although alb-SREBP-1a mice develop a severe phenotype with visceral adipositas and hepatic lipid accumulation featuring a fatty liver, the hepatic differential gene expression and alterations in peroxisomal protein patterns compared to control mice were surprisingly relative low. In contrast, phosphorylation site deficient alb-SREBP-1a∆P mice, protected from hepatic lipid accumulation phenotype, showed gross alteration in hepatic gene expression and peroxisomal proteome. Further knowledge based analyzes revealed that overexpression of SREBP-1a favored mainly acceleration in lipid metabolism and indicated a regular insulin signaling, whereas disruption of SREBP-1a phosphorylation resulted in massive alteration of cellular processes including signs for loss of lipid metabolic targets. These results could be the link to a disturbed lipid metabolism that overall resembles a state of insulin resistance.
2018-03-30 | GSE110569 | GEO
Project description:The determination of molecular pathways that are affected with age and lead to increased disease susceptibility is crucial. The nematode has proven an ideal experimental model to study ageing due to significantly conserved genes governing ageing throughout species. Profiling of gene expression levels in ageing wt Caenorhabditis elegans, utilizing a robust Affymetrix microarray platform, resulted in the identification of age-dependent gene expression alterations that characterize the nematode's ageing process. We used Affymetrix microarrays to detail the global programme of gene expression underlying ageing and identified distinct classes of up- or down-regulated genes during this process.
2023-12-14 | GSE163253 | GEO