Age dependent gene and transposon expression in male wildtype (wDAH) and FOXO deletion (wDAH ∆94) fly strains.
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE205416 | GEO | 2022/08/01
REPOSITORIES: GEO
Similar Datasets
Project description:FOXO transcription factors control numerous pathways involving metabolism, stress response, and longevity. Although direct targets of FOXO have been reported in various long-lived mutants and under stress conditions, no studies have investigated how normal aging impacts the cellular activity of FOXO. In this study, we compared genome wide dFOXO-bound sites in young and aged wild-type flies kept under normal feeding conditions to evaluate the dynamics of FOXO gene targeting during aging. Our results provide a new insight into FOXO chromatin targeting under a normal aging model and highlight the diverse regulatory mechanisms for FOXO transcriptional activity that are currently less understood.
2019-04-25 | GSE121102 | GEO
Project description:We performed RNA-seq for WT and foxo mutant flies, by combining with Dr. Baihua's foxo chip-seq data, we found 101 foxo-repressed and 300 foxo-activated genes. By analyzing expression change of these genes during age, we found foxo-repressed genes became activated, while foxo-activated genes became repressed, suggesting foxo signaling declines with age.
2018-11-14 | GSE122470 | GEO
Project description:Skeletal muscle senescence influences whole organism aging, yet little is known on the relay of pro-longevity signals from muscles to other tissues. We performed an RNAi screen in Drosophila for muscle-released cytokines ('myokines') regulating lifespan and identified Myoglianin, the homolog of human Myostatin. Myoglianin is induced in skeletal muscles by the transcription factor Mnt and together they constitute an inter-organ signaling module that regulates lifespan, age-related muscle dysfunction, and protein synthesis across aging tissues. Both Mnt and Myoglianin activate already in young age the protective decline in protein synthesis that is typical of old age, while knock-down of Myoglianin impairs this process. Mechanistically, Mnt decreases the expression of nucleolar components in muscles while also decreasing nucleolar size in distant tissues via Myostatin/p38 MAPK signaling. Our results highlight a myokine-dependent inter-organ longevity pathway that coordinates nucleolar function and protein synthesis across aging tissues. Affymetrix microarrays were used to evaluate genome-wide expression in skeletal muscles of flies with muscle-specific overexpression of FOXO or Mnt (Affymetrix Drosophila Genome 2.0 Array). This design allowed us to identify genes and pathways induced by overexpression of FOXO and/or Mnt, and enabled us to address the degree to which FOXO-induced pathways were independent of those induced by Mnt. Three independent biological replicates from each of three groups (control, UAS-Foxo and UAS-Mnt)
2014-07-02 | E-GEOD-39877 | biostudies-arrayexpress
Project description:FoxO transcription factors promote longevity across taxa. How they do so is poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms of the FoxO transcription factor DAF-16 extend life span in the context of reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed an integrative analysis of isoform-specific daf-16/FoxO mutants. In contrast to previous studies suggesting that DAF-16F plays a more prominent role in life span control than DAF-16A, isoform-specific daf-16/FoxO mutant phenotypes and whole transcriptome profiling revealed a predominant role for DAF-16A over DAF-16F in life span control, stress resistance, and target gene regulation. Integration of these data sets enabled the prioritization of a subset of 92 DAF-16/FoxO target genes for functional interrogation. Among 29 genes tested, two DAF-16A-specific target genes significantly influenced longevity. Our discovery of new longevity genes underscores the efficacy of our integrative strategy while providing a general framework for identifying specific downstream gene regulatory events that contribute substantially to transcription factor functions. As FoxO transcription factors have conserved functions in promoting longevity and may be dysregulated in aging-related diseases, these findings promise to illuminate fundamental principles underlying aging in animals. Whole-transcriptome profiling of daf-16/FoxO isoform-specific deletion mutants in the long-lived daf-2(e1370) background. Included are daf-16 wild-type, daf-16 null mutation, daf-16a/f mutation, two independent daf-16a mutations, and daf-16f mutation. N2 wild-type controls are also included.
2015-08-27 | E-GEOD-72426 | biostudies-arrayexpress
Project description:Molecular aging reflects the time-dependent accumulation of cellular damage and loss of essential cellular functions. FOXO transcription factors and their downstream targets play critical roles in the response to aging-associated cellular damage. Here, we identify and characterize a novel FOXO-regulated stress response gene, Oxidative Stress Responsive Serine-rich Protein 1 (OSER1), whose level of expression dramatically influences lifespan in Bombyx mori, Caenorhabditis elegans, and Drosophila. Overexpression of OSER1 also enhances resistance to oxidative stress, starvation, and heat shock, whereas depletion increases susceptibility to these stressors. In humans, common OSER1 genetic variants are associated with longevity. These data show that OSER1 modulates the oxidative stress response and suggest that OSER1 is a potent positive regulator of lifespan and healthspan in multiple species.
2024-07-25 | PXD036579 | Pride
Project description:Age dependent gene and transposon expression in male wildtype (wDAH) and FOXO deletion (wDAH ∆94) fly strains.
| PRJNA844987 | ENA
Project description:FoxO transcription factors promote longevity across taxa. How they do so is poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms of the FoxO transcription factor DAF-16 extend life span in the context of reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed an integrative analysis of isoform-specific daf-16/FoxO mutants. In contrast to previous studies suggesting that DAF-16F plays a more prominent role in life span control than DAF-16A, isoform-specific daf-16/FoxO mutant phenotypes and whole transcriptome profiling revealed a predominant role for DAF-16A over DAF-16F in life span control, stress resistance, and target gene regulation. Integration of these data sets enabled the prioritization of a subset of 92 DAF-16/FoxO target genes for functional interrogation. Among 29 genes tested, two DAF-16A-specific target genes significantly influenced longevity. Our discovery of new longevity genes underscores the efficacy of our integrative strategy while providing a general framework for identifying specific downstream gene regulatory events that contribute substantially to transcription factor functions. As FoxO transcription factors have conserved functions in promoting longevity and may be dysregulated in aging-related diseases, these findings promise to illuminate fundamental principles underlying aging in animals.
2015-08-27 | GSE72426 | GEO
Project description:Skeletal muscle senescence influences whole organism aging, yet little is known on the relay of pro-longevity signals from muscles to other tissues. We performed an RNAi screen in Drosophila for muscle-released cytokines (?myokines?) regulating lifespan and identified Myoglianin, the homolog of human Myostatin. Myoglianin is induced in skeletal muscles by the transcription factor Mnt and together they constitute an inter-organ signaling module that regulates lifespan, age-related muscle dysfunction, and protein synthesis across aging tissues. Both Mnt and Myoglianin activate already in young age the protective decline in protein synthesis that is typical of old age, while knock-down of Myoglianin impairs this process. Mechanistically, Mnt decreases the expression of nucleolar components in muscles while also decreasing nucleolar size in distant tissues via Myostatin/p38 MAPK signaling. Our results highlight a myokine-dependent inter-organ longevity pathway that coordinates nucleolar function and protein synthesis across aging tissues. Affymetrix microarrays were used to evaluate genome-wide expression in skeletal muscles of flies with muscle-specific overexpression of FOXO or Mnt (Affymetrix Drosophila Genome 2.0 Array). This design allowed us to identify genes and pathways induced by overexpression of FOXO and/or Mnt, and enabled us to address the degree to which FOXO-induced pathways were independent of those induced by Mnt.
2014-07-02 | GSE39877 | GEO
Project description:Purpose: REPTOR and FoxO are two transcription factors that regulate muscle metabolism. However, these transcription factors share around 40% of target genes. Furthermore, the thorax of adult flies is composed of several tissues including muscle and fat body, making it difficult to discover direct target genes of REPTOR and FoxO specifically in muscle tissue. This experimental approach allows the identification of REPTOR-specific and FoxO-specific target genes in muscle clusters Methods: snRNA-seq analysis of dissected adult fly thoraces, when an active allele of REPTOR or an active allele of FoxO are overexpressed using a muscle-specific driver (dMef2-Gal4) Results: Identification of the transcriptional signature of each tissue present in the thorax of adult flies when REPTOR or FoxO are overexpressed in muscle. Discovery of potential direct target genes of REPTOR and FoxO in muscle tissue, as well as metabolic pathways regulated by each transcription factor. Conclusions: REPTOR and FoxO modulate distinct gene signatures in muscle tissue to regulate metabolism in adult flies.
2023-06-01 | GSE227038 | GEO
Project description:Innate immunity is a highly reactive response aiming at clearing pathogens. Abnormal induction of innate immune genes can lead to deleterious consequences to the host. However, little is known about the intrinsic signaling pathway that prohibits constitutive activation of innate immunity. Here using fruit flies, we profile the microRNA targetomes in young and aged animals. We demonstrate FoxO, and miR-252 inhibit spontaneous induction of innate immunity by repressing Daw. We further determine the signaling cascade by which Daw causes the reduction of Atg8a-mediated selective autophagy on kenny protein, which in turn activates Relish protein and consequential upregulation of innate immune genes. Finally, while aging leads to a decline in FOXO signaling activity concomitant with a progressive induction of innate immune genes, transgenic increase of FoxO, miR-252, and Atg8a in wild-type Drosophila promotes longevity and mitigates the expression of age-onset innate immune genes. Together, we propose that FoxO and miR-252 define a pro-survival mechanism by inhibiting constitutive innate immunity.
2018-12-31 | GSE124504 | GEO