Dietary Restriction Impacts Peripheral Circadian Clock Output Important for Longevity in Drosophila
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ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE145509 | GEO | 2026/03/10
REPOSITORIES: GEO
Similar Datasets
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 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) 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:Dietary restriction (DR) is a well-established method for extending lifespan across various species, including C. elegans. Among the different DR regimens, axenic dietary restriction (ADR), in which worms are grown in a nutrient-rich sterile liquid medium, yields the most powerful lifespan extension. However, the molecular mechanisms underlying this longevity phenotype remain largely unexplored. Through a pilot screen of candidate genes, we identified the proprotein convertase BLI-4 as a crucial factor in neurons for modulating lifespan under ADR conditions. BLI-4's role appears to be specific to ADR, as it does not significantly impact longevity under other DR regimens.
2025-07-21 | PXD053074 | Pride
Project description:The mammalian circadian clock relies on the master genes CLOCK (CLK) and BMAL1 and drives rhythmic gene expression to regulate biological functions under circadian control. We recently uncovered a surprising disconnect between the rhythmic binding of CLK:BMAL1 on DNA and the transcription of its target genes, suggesting that they are regulated by as yet uncharacterized mechanisms. Here we show that rhythmic CLK:BMAL1 DNA binding promotes rhythmic chromatin opening. The underlying mechanisms include CLK:BMAL1 binding to nucleosomes and rhythmic chromatin modifications, including the incorporation of the histone variant H2A.Z. This rhythmic chromatin remodeling mediates the rhythmic binding of other transcription factors adjacent to CLK:BMAL1, suggesting that the activity and the tissue-specific expression of these other transcription factors contribute to the genome-wide CLK:BMAL1 heterogeneous transcriptional output. These data therefore indicate that the clock regulation of transcription relies on the rhythmic regulation of chromatin accessibility and suggest that the concept of pioneer function extends to acute gene regulation, well beyond the current confines of developmental/cell specification. H2A.Z ChIP-Seq signal in the mouse liver over 6 time points of the 24h light:dark cycle, in wild-type and Bmal1-/- mice. Libraries containing a mononucleosome insert were sequenced using Ilumina HiSeq2000.
2014-01-06 | E-GEOD-47143 | biostudies-arrayexpress
Project description:The mammalian circadian clock relies on the master genes CLOCK (CLK) and BMAL1 and drives rhythmic gene expression to regulate biological functions under circadian control. We recently uncovered a surprising disconnect between the rhythmic binding of CLK:BMAL1 on DNA and the transcription of its target genes, suggesting that they are regulated by as yet uncharacterized mechanisms. Here we show that rhythmic CLK:BMAL1 DNA binding promotes rhythmic chromatin opening. The underlying mechanisms include CLK:BMAL1 binding to nucleosomes and rhythmic chromatin modifications, including the incorporation of the histone variant H2A.Z. This rhythmic chromatin remodeling mediates the rhythmic binding of other transcription factors adjacent to CLK:BMAL1, suggesting that the activity and the tissue-specific expression of these other transcription factors contribute to the genome-wide CLK:BMAL1 heterogeneous transcriptional output. These data therefore indicate that the clock regulation of transcription relies on the rhythmic regulation of chromatin accessibility and suggest that the concept of pioneer function extends to acute gene regulation, well beyond the current confines of developmental/cell specification. Mouse liver nucleosome profile assayed by MNase-Seq over 6 time points of the 24h light:dark cycle (4 wild-type and 4 Bmal1-/- mice per time point). Illumina libraries containing a mononucleosome insert were sequenced using Ilumina HiSeq2000.
2014-01-06 | E-GEOD-47142 | biostudies-arrayexpress
Project description:The mammalian circadian clock relies on the master genes CLOCK (CLK) and BMAL1 and drives rhythmic gene expression to regulate biological functions under circadian control. We recently uncovered a surprising disconnect between the rhythmic binding of CLK:BMAL1 on DNA and the transcription of its target genes, suggesting that they are regulated by as yet uncharacterized mechanisms. Here we show that rhythmic CLK:BMAL1 DNA binding promotes rhythmic chromatin opening. The underlying mechanisms include CLK:BMAL1 binding to nucleosomes and rhythmic chromatin modifications, including the incorporation of the histone variant H2A.Z. This rhythmic chromatin remodeling mediates the rhythmic binding of other transcription factors adjacent to CLK:BMAL1, suggesting that the activity and the tissue-specific expression of these other transcription factors contribute to the genome-wide CLK:BMAL1 heterogeneous transcriptional output. These data therefore indicate that the clock regulation of transcription relies on the rhythmic regulation of chromatin accessibility and suggest that the concept of pioneer function extends to acute gene regulation, well beyond the current confines of developmental/cell specification. Mouse liver CLK ChIP-Seq signal on Mnase-digested or sonicated chromatin, at 2 different time point (ZT22 and ZT06) from the same mice. Libraries were sequenced using Ilumina HiSeq2000. For Mnase-digested chromatin, libraries contained a mononucleosome insert (e.g., ~147bp), whereas the insert was ~150-300bp for sonicated chromatin.
2014-01-06 | E-GEOD-47144 | biostudies-arrayexpress
Project description:Liver circadian clock and daily rhythmic transcriptome are highly responsive to metabolic cues generated from daily feeding activity. The mechanisms that mediate metabolic inputs to the whole rhythmic transcriptome are still under investigation. Here, we explored the role of O-GlcNAcylation, a nutrient-sensitive post-translational modification (PTM) that integrates circadian and metabolic signals, in the diurnal regulation of nuclear proteins. We found daily oscillation of overall nuclear protein O-GlcNAcylation in the liver of mice subjected to natural night time-restricted feeding (NRF). O-GlcNAcomic analysis revealed that 11.54% of 719 O-GlcNAcylated proteins are rhythmically O-GlcNAcylated. Proteins involved in gene expression were enriched, suggesting rhythmic O-GlcNAcylation may directly shape diurnal transcriptome. Furthermore, we showed that rhythmic O-GlcNAcylation could indirectly modulate diurnal transcriptome by interacting with phosphorylation. Specifically, several proteins harboring O-GlcNAcylation-phosphorylation interplay motif exhibit rhythmic O-GlcNAcylation and phosphorylation. For example, O-GlcNAcylation may occur at a phosphor-degron of a key circadian transcriptional activator, circadian locomotor output cycles kaput (CLOCK), regulating the stability and transcriptional output of CLOCK. Lastly, unnatural day time-restricted feeding (DRF) dampens O-GlcNAcylation rhythm, suggesting the disruption of diurnal transcriptome could be mediated by protein O-GlcNAcylation. In summary, our results provide mechanistic insights into metabolic regulation of diurnal transcriptome at PTM level and shed light on the deleterious effects of improper mealtimes.
2024-03-27 | MSV000094417 | MassIVE
Project description:The mammalian circadian clock relies on the master genes CLOCK (CLK) and BMAL1 and drives rhythmic gene expression to regulate biological functions under circadian control. We recently uncovered a surprising disconnect between the rhythmic binding of CLK:BMAL1 on DNA and the transcription of its target genes, suggesting that they are regulated by as yet uncharacterized mechanisms. Here we show that rhythmic CLK:BMAL1 DNA binding promotes rhythmic chromatin opening. The underlying mechanisms include CLK:BMAL1 binding to nucleosomes and rhythmic chromatin modifications, including the incorporation of the histone variant H2A.Z. This rhythmic chromatin remodeling mediates the rhythmic binding of other transcription factors adjacent to CLK:BMAL1, suggesting that the activity and the tissue-specific expression of these other transcription factors contribute to the genome-wide CLK:BMAL1 heterogeneous transcriptional output. These data therefore indicate that the clock regulation of transcription relies on the rhythmic regulation of chromatin accessibility and suggest that the concept of pioneer function extends to acute gene regulation, well beyond the current confines of developmental/cell specification.
2014-01-06 | GSE47144 | GEO
Project description:The mammalian circadian clock relies on the master genes CLOCK (CLK) and BMAL1 and drives rhythmic gene expression to regulate biological functions under circadian control. We recently uncovered a surprising disconnect between the rhythmic binding of CLK:BMAL1 on DNA and the transcription of its target genes, suggesting that they are regulated by as yet uncharacterized mechanisms. Here we show that rhythmic CLK:BMAL1 DNA binding promotes rhythmic chromatin opening. The underlying mechanisms include CLK:BMAL1 binding to nucleosomes and rhythmic chromatin modifications, including the incorporation of the histone variant H2A.Z. This rhythmic chromatin remodeling mediates the rhythmic binding of other transcription factors adjacent to CLK:BMAL1, suggesting that the activity and the tissue-specific expression of these other transcription factors contribute to the genome-wide CLK:BMAL1 heterogeneous transcriptional output. These data therefore indicate that the clock regulation of transcription relies on the rhythmic regulation of chromatin accessibility and suggest that the concept of pioneer function extends to acute gene regulation, well beyond the current confines of developmental/cell specification.
2014-01-06 | GSE47143 | GEO