Similar Datasets
Project description:Circadian clocks may mediate lifespan extension by caloric or dietary restriction (DR). We find that the core clock transcription factor Clock is crucial for a robust longevity and fecundity response to DR in Drosophila. To identify clock-controlled mediators, we performed RNA-sequencing from abdominal fat bodies across the 24 h day after just 5 days under control or DR diets. In contrast to more chronic DR regimens, we did not detect significant changes in the rhythmic expression of core clock genes. Yet we discovered that DR induced de novo rhythmicity or increased expression of rhythmic clock output genes. Network analysis revealed that DR increased network connectivity in one module comprised of genes encoding proteasome subunits. Adult, fat body specific RNAi knockdown demonstrated that proteasome subunits contribute to DR-mediated lifespan extension. Thus, clock control of output links DR-mediated changes in rhythmic transcription to lifespan extension. Funding: DARPA D12AP00023
2026-03-10 | GSE145509 | GEO
Project description:Dietary restriction (DR) is a robust environmental intervention that slows aging in various species. Changes in fat content have been associated with DR, but whether they play a causal role in mediating various responses to DR remains unknown. We demonstrate that upon DR, Drosophila melanogaster shift their metabolism towards increasing both fatty acid synthesis and breakdown. Inhibition of acetyl CoA carboxylase (ACC), a critical enzyme in fatty acid synthesis, or fatty acid oxidation genes specifically in the muscle tissue inhibited the lifespan extension observed upon DR, suggesting a critical role for intra-myocellular fatty acid metabolism. DR enhances spontaneous activity of flies which was found to be dependent on the enhanced fatty acid metabolism. Furthermore, this increase in activity upon DR was found to partially mediate the lifespan extension upon DR. Over-expression of adipokinetic hormone (dAKH) in whole flies, which increases fat metabolism, led to an increase in spontaneous activity and lifespan in a nutrient dependent manner. Together these results suggest that in Drosophila melanogaster enhanced fat metabolism in the muscle is a key metabolic adaptation in response to DR.
2012-06-15 | GSE37537 | GEO
Project description:Dietary restriction (DR) is the best-characterized intervention for slowing aging, and reduced signaling through the target of rapamycin (TOR) kinase is believed to be one of the key mechanisms by which DR extends life span in organisms from yeast to mammals. Here we describe a role for nuclear sequestration of tRNA in yeast replicative life span (RLS) extension from DR. DR causes the nuclear tRNA exporter Los1 to become depleted from the nucleus by a mechanism that requires the DNA damage response factor Rad53, and deletion of LOS1 or overexpression of RAD53 is sufficient to extend RLS. We further report that activation of the nitrogen responsive transcription factor Gln3 is the primary mechanism by which DR extends RLS. Gln3 is activated by both branches of the DR response and is required for life span extension. Overexpression of Gln3 extends RLS by approximately 50%.
2015-02-03 | GSE37241 | GEO
Project description:Dietary restriction (DR) is a robust environmental intervention that slows aging in various species. Changes in fat content have been associated with DR, but whether they play a causal role in mediating various responses to DR remains unknown. We demonstrate that upon DR, Drosophila melanogaster shift their metabolism towards increasing both fatty acid synthesis and breakdown. Inhibition of acetyl CoA carboxylase (ACC), a critical enzyme in fatty acid synthesis, or fatty acid oxidation genes specifically in the muscle tissue inhibited the lifespan extension observed upon DR, suggesting a critical role for intra-myocellular fatty acid metabolism. DR enhances spontaneous activity of flies which was found to be dependent on the enhanced fatty acid metabolism. Furthermore, this increase in activity upon DR was found to partially mediate the lifespan extension upon DR. Over-expression of adipokinetic hormone (dAKH) in whole flies, which increases fat metabolism, led to an increase in spontaneous activity and lifespan in a nutrient dependent manner. Together these results suggest that in Drosophila melanogaster enhanced fat metabolism in the muscle is a key metabolic adaptation in response to DR. 24 experimental samples were analyzed using Nimblegen oligo microarrays. Wild type samples (AL without RU486) were used as the Cy3 reference/control for all experimetal comparisons.
2012-06-14 | E-GEOD-37537 | biostudies-arrayexpress
Project description:Dietary restriction (DR) is the best-characterized intervention for slowing aging, and reduced signaling through the target of rapamycin (TOR) kinase is believed to be one of the key mechanisms by which DR extends life span in organisms from yeast to mammals. Here we describe a role for nuclear sequestration of tRNA in yeast replicative life span (RLS) extension from DR. DR causes the nuclear tRNA exporter Los1 to become depleted from the nucleus by a mechanism that requires the DNA damage response factor Rad53, and deletion of LOS1 or overexpression of RAD53 is sufficient to extend RLS. We further report that activation of the nitrogen responsive transcription factor Gln3 is the primary mechanism by which DR extends RLS. Gln3 is activated by both branches of the DR response and is required for life span extension. Overexpression of Gln3 extends RLS by approximately 50%. In order to identify potential factors acting to modulate longevity downstream of Los1, we used microarray analysis to compare the gene expression profiles of wild type and LOS1 knockout cells under non-restricted conditions cultured overnight prior to RNA isolation.
2015-02-03 | E-GEOD-37241 | biostudies-arrayexpress
Project description:Dietary restriction (DR) has been shown to increase lifespan in organisms ranging from yeast to mammals. This suggests that the underlying mechanisms may be evolutionarily conserved. Indeed, upstream signalling pathways, such as TOR, are strongly linked to DR-induced longevity in various organisms. However, the downstream effector proteins that ultimately mediate lifespan extension are less clear. To shed light on this, we used a proteomic approach on budding yeast. Our reasoning was that analysis of proteome-wide changes in response to DR might enable the identification of proteins that mediate its physiological effects, including lifespan extension. Of over 2500 proteins we identified by liquid chromatography-mass spectrometry, 183 were significantly altered in expression by at least 3-fold in response to DR. Most of these proteins were mitochondrial and/or had clear links to respiration and metabolism. Indeed, direct analysis of oxygen consumption confirmed that mitochondrial respiration was increased several-fold in response to DR. In addition, several key proteins involved in mating, including Ste2 and Ste6, were downregulated by DR. Consistent with this, shmoo formation in response to α-factor pheromone was reduced by DR, thus confirming the inhibitory effect of DR on yeast mating. Finally, we found that Hsp26, a member of the conserved small heat shock protein (sHSP) family, was upregulated by DR and that overexpression of Hsp26 extends yeast replicative lifespan. As overexpression of sHSPs in C. elegans and Drosophila has previously been shown to extend lifespan, our data on yeast Hsp26 suggest that sHSPs may be universally conserved effectors of longevity.
2022-02-17 | PXD025004 | Pride
Project description:Expression data from four different lifespan-extending conditions: dietary restriction in two different genetic backgrounds (canton-s and a yw, w1118 combination), sir2 overexpression and p53 knockdown (+/-). Comparison of significantly over and under-expressed genes reveals a signature for dietary restriction and lifespan extension. Abstract A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular genetic life span extending interventions related to DR, increased dSir2 and decreased Dmp53 activity. We find twenty-one genes shared among the three related life span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah. We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway.
2011-01-20 | GSE26726 | GEO