DSirt6 Regulates Lifespan in Drosophila
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA790977 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Sirt6 is a multifunctional enzyme that regulates diverse cellular processes such as metabolism, DNA repair, and aging. Overexpressing Sirt6 extends lifespan in mice, but the underlying cellular mechanisms are unclear. Drosophila melanogaster are an excellent model to study genetic regulation of lifespan; however, despite extensive study in mammals, very little is known about Sirt6 function in flies. Here, we characterized the Drosophila ortholog of Sirt6, dSirt6, and examined its role in regulating longevity. dSirt6 is a nuclear and chromatin-associated protein with NAD+-dependent histone deacetylase activity. dSirt6 overexpression in flies produces robust lifespan extension in both sexes, while reducing dSirt6 levels shortens lifespan. dSirt6 OE flies have normal food consumption and fertility, but increased resistance to oxidative stress and reduced protein synthesis rates. Transcriptomic analyses reveal that dSirt6 OE reduces expression of genes involved in ribosome biogenesis, including many dMyc target genes. dSirt6 OE partially rescues many effects of dMyc OE, including increased nuclear size, up-regulation of ribosome biogenesis genes, and lifespan shortening. Lastly, dMyc haploinsufficiency does not convey additional lifespan extension to dSirt6 OE flies, suggesting dSirt6 OE is upstream of dMyc in regulating lifespan. Our results provide new insight into the mechanisms by which Sirt6 overexpression leads to longer lifespan.
2021-12-23 | GSE191320 | GEO
Project description:An insulin-sensitive circular RNA that regulates lifespan in Drosophila
| PRJNA534114 | ENA
Project description:Aging is associated with extensive remodeling of the heart, including basement membrane (BM) components that surround cardiomyocytes. Remodeling is thought to impair cardiac mechanotransduction, but the contribution of specific BM components to age-related lateral communication between cardiomyocytes is unclear. Using a genetically tractable, rapidly aging model with sufficient cardiac genetic homology and morphology, e.g. Drosophila melanogaster, we observed differential regulation of BM collagens between laboratory strains, correlating with changes in muscle physiology leading to cardiac dysfunction. Therefore, we sought to understand the extent to which BM proteins modulate contractile function during aging. Cardiac-restricted knockdown of ECM genes Pericardin, Laminin A, and Viking in Drosophila prevented age-associated heart tube restriction and increased contractility, even under viscous load. Most notably, reduction of Laminin A expression correlated with an overall preservation of contractile velocity with age and extension of organismal lifespan. Global heterozygous knockdown confirmed these data, which provides new evidence of a direct link between BM homeostasis, contractility, and maintenance of lifespan.
2017-03-27 | PXD006120 | Pride
Project description:Primary bile acids are produced in the liver whereas secondary bile acids such as lithocholic acid (LCA) are generated by gut bacteria from primary bile acids that escape the ileal absorption. Besides their well-known function as detergents in lipid digestion, bile acids are important signaling molecules mediating effects on the host’s metabolism. As energy metabolism is closely linked to aging and longevity we supplemented fruit flies (Drosophila melanogaster) with 50 µmol/l LCA either for 30 days or throughout their lifetime. LCA supplementation resulted in a significant induction of the mean (+12 days), median (+10 days) and maximum lifespan (+ 11 days) in comparison to untreated control flies. This lifespan extension was accompanied by an induction of spargel (srl), the fly homolog of mammalian PPARG co-activator 1a(PGC1A. In srl mutant flies, LCA failed to induce longevity emphasizing the essential role of srl in the observed lifespan extension. In addition, the administration of antibiotics to wild type flies abrogated LCA-mediated effects on both lifespan and srl expression, suggesting a substantial contribution of the intestinal microbiota to the LCA-induced longevity. In the present study, we show that the secondary bile acid LCA significantly induced the mean, the median and the maximum survival in Drosophila melanogaster. Our data suggest that besides an up-regulation of the PGC1a-homolog srl unidentified alterations in the structure or metabolism of gut microbiota contribute to the longevity effect of LCA.
2018-08-03 | GSE110367 | GEO
Project description:Our data describes the first atlas of long-lived proteins in somatic and reproductive tissues of Drosophila during adult lifespan, and reveals a preferential ubiquitylation in the aging proteome.
2019-03-15 | PXD013101 | iProX
Project description:Drosophila Lnk is the single ancestral orthologue of a highly conserved family of structurally-related intracellular adaptor proteins, the SH2B proteins. As adaptors, they lack catalytic activity but contain several protein-protein interaction domains, thus playing a critical role in signal transduction from receptor tyrosine kinases to form protein networks. Physiological studies of SH2B function in mammals have produced conflicting data. However, a recent study in Drosophila has shown that Lnk is an important regulator of the insulin/insulin-like growth factor (IGF)-1 signaling (IIS) pathway during growth, functioning in parallel to the insulin receptor substrate, Chico. As this pathway also has an evolutionary conserved role in the determination of organism lifespan, we investigated whether Lnk is required for normal lifespan in Drosophila. Phenotypic analysis of mutants for Lnk revealed that loss of Lnk function results in increased lifespan and improved survival under conditions of oxidative stress and starvation. Starvation resistance was found to be associated with increased metabolic stores of carbohydrates and lipids indicative of impaired metabolism. Biochemical and genetic data suggest that Lnk functions in both the IIS and Ras/Mitogen activated protein Kinase (MapK) signaling pathways. Microarray studies support this model, showing transcriptional feedback onto genes in both pathways as well as indicating global changes in both lipid and carbohydrate metabolism. Finally, our data also suggest that Lnk itself may be a direct target of the IIS responsive transcription factor, dFoxo, and that dFoxo may repress Lnk expression. We therefore describe novel functions for a member of the SH2B protein family and provide the first evidence for potential mechanisms of SH2B regulation. Our findings suggest that IIS signaling in Drosophila may require the activity of a second intracellular adaptor, thereby yielding fundamental new insights into the functioning and role of the IIS pathway in ageing and metabolism.
2016-03-30 | E-MTAB-4612 | biostudies-arrayexpress
Project description:Atf-6 regulates lifespan through ER-mitochondrial calcium homeostasis
| PRJNA656523 | ENA
Project description:Lithocholic acid significantly extends the lifespan in Drosophila melanogaster by targeting multiple lifespan-extending pathways
| PRJNA433535 | ENA
Project description:The mitochondrial unfolded protein response (UPRmt) has been associated with long lifespan across metazoans. In Caenorhabditis elegans, mild developmental mitochondrial stress activates UPRmt reporters and extends lifespan. We show that similar developmental stress is necessary and sufficient to extend Drosophila lifespan, and identify Phosphoglycerate Mutase 5 (PGAM5) as a mediator of this response. Developmental mitochondrial stress leads to activation of FoxO, via Apoptosis Signal-regulating Kinase 1 (ASK1) and Jun-N-terminal Kinase (JNK). This activation persists into adulthood and induces a select set of chaperones, many of which have been implicated in lifespan extension in flies. Persistent FoxO activation can be reversed by a high- protein diet in adulthood, through mTORC1 and GCN-2 activity. Accordingly, the observed lifespan extension is prevented on a high-protein diet and in FoxO-null flies. The diet-sensitivity of this pathway has important implications for interventions that seek to engage the UPRmt to improve metabolic health and longevity.
2017-10-25 | GSE106105 | GEO
Project description:Manipulating the activity of transcription factor (TF) to regulate animal’s longevity is achieved in different species. However, deciphering the pro-longevity transcriptional programme triggered by the TFs activity is challenging. One obstacle is the multifunctional feature of TFs. The physiological functions of single TF could be diverse and tissues-dependent. The other is the gene regulatory network among the TFs, where multiple TFs can have synergetic or antagonistic impact on the same target genes. Here, we show Xbp1s overexpression in gut and fat body can extend lifespan in Drosophila. Importantly, Xbp1s activity triggers distinct transcriptional programmes in the two tissues, and Xbp1s induction in both tissues are beneficial for longevity. Furthermore, we reveal a pro-longevity gene regulatory network in the fat body, where Xbp1s and dFOXO impinge on the same target genes and induce identical transcriptional outcomes. dfoxo overexpression requires Xbp1 to extend lifespan. Lastly, inducing Xbp1u, the precursor of Xbp1s, can also extend lifespan without triggering massive transcriptome change.
2024-05-06 | GSE246232 | GEO