RNA sequencing of mouse hepatic response to compounds with predicted lifespan-extending effect
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA545143 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9137550.fastq.gz | Fastqsanger.gz | |||
| SRR9137560.fastq.gz | Fastqsanger.gz | |||
| SRR9137551.fastq.gz | Fastqsanger.gz | |||
| SRR9137561.fastq.gz | Fastqsanger.gz | |||
| SRR9137552.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:This dataset consists of hepatic gene expression profiles of mice subjected to 4 compounds predicted by Connectivity Map (CMap) using gene signatures identified for known lifespan-extending interventions: ascorbyl-palmitate, KU-0063794, AZD8055 and rilmenidine. Corresponding age-, sex- and strain-matched littermate controls are also presented. Using this data, we confirmed the association between longevity signatures and gene expression response to the predicted compounds in vivo, using the same mouse model as for the identification of gene signatures associated with lifespan extension. This pilot project demonstrated the applicability of such approach for the discovery of new interventions with a desirable effect on gene expression and provided appealing candidates for further longevity studies.
2019-07-25 | GSE131868 | GEO
Project description:RNA sequencing of mouse hepatic response to lifespan-extending interventions
| PRJNA544682 | ENA
Project description:This dataset consists of hepatic gene expression profiles of mice subjected to 8 different lifespan-extending interventions, together with the corresponding age-, sex- and strain-matched littermate controls: caloric restriction (CR), methionine restriction (MR), growth hormone receptor knockout (GHRKO), Snell dwarf mice (Pit1 -/-), rapamycin, acarbose, 17-alpha-estradiol (17aE2) and Protandim. Both sexes and different age groups are presented within dataset. Using this data, we identified general and specific gene expression patterns associated with lifespan extension. We detected a feminization effect associated with growth hormone regulation and diminution of sex-related differences in response to many interventions at transcriptome and metabolome levels. Combining the dataset with publicly available resources, we found that many interventions exhibited similar transcriptome changes, whereas some, including rapamycin, showed distinct patterns. We identified common hepatic signatures of lifespan extension, e.g. upregulation of oxidative phosphorylation and NRF2-regulated enzymes, and found that many perturbed pathways are shared across tissues. Moreover, the response of genes related to glucose metabolism and immune function represented both qualitative and quantitative associations with longevity. Finally, we used the detected longevity signatures to identify new candidates for lifespan extension and built GENtervention, a tool that visualizes associations of gene expression responses with lifespan extension.
2019-07-25 | GSE131754 | GEO
Project description:Aging manifests as progressive deterioration in cellular and systemic homeostasis, requiring systems-level perspectives to understand the gradual molecular dysregulation of underlying biological processes. Here, we collected data for the analysis of systems-level changes in the molecular regulation of biological processes under multiple lifespan-extending interventions in mice. High-resolution shotgun LC-MS/MS data were collected from liver samples obtained from multiple mouse cohorts treated with different lifespan-extending drugs, and analyzed using reverse phase liquid chromatography on Orbitrap mass spectrometers.
2023-07-25 | PXD035255 | Pride
Project description:Lithocholic acid significantly extends the lifespan in Drosophila melanogaster by targeting multiple lifespan-extending pathways
| PRJNA433535 | ENA
Project description:Induction of proteasomal activity in mammalian cells by lifespan-extending tRNA synthetase inhibitors
| PRJNA899861 | ENA
Project description:One of the most important issues in the study of aging is to discover compounds with longevity-promoting activity and to unravel their underlying mechanisms. Queen honey bees are continuously fed royal jelly (RJ), and they live more than 10 times longer than hive workers, derived from the same diploid genome, which are fed it only for a short period of time during their larval stages. Therefore, RJ is likely to contain longevity-promoting agents for queens. RJ has been reported to possess diverse pharmacological properties. Furthermore, protease-treated RJ (pRJ) has additional beneficial activities. How RJ and pRJ exert these effects and which components in them play a critical role is largely unknown. The evolutionally conserved mechanisms that control lifespan have been indicated. The nematode Caenorhabditis elegans has been widely used for study of aging and longevity, due to its relatively short lifespan and well-established genetic pathways. The purpose of the present study was to elucidate whether RJ and its related substances contain the life span-extending activity in C. elegans and to obtain some insight into the active agents and their mechanisms. We found that both RJ and pRJ extended the lifespan of C. elegans. The life span-extending activity of pRJ was enriched by ODS column chromatography (pRJ-Fraction 5). pRJ-Fr. 5 extended the life span partly by acting through the FOXO transcription factor DAF-16, the activation of which is known to promote longevity in C. elegans by reducing insulin/IGF-1 signaling (IIS). pRJ-Fr. 5 induced changes in the expression of 3 genes encoding insulin-like peptides. Moreover, pRJ-Fr. 5 and reduced IIS shared some common features in terms of their effect on gene expression, such as up-regulation of dod-3 and down-regulation of dod-19, dao-4 and fkb-4. The dod-19 is a previously identified life span determinant in C. elegans, and the fkb-4 encodes a homologue of the mammalian FK506-binding protein. 10-Hydroxy-2-decenoic acid (10-HDA), which was present in high concentration in pRJ-Fr. 5, increased the lifespan independently of DAF-16 activity.These results demonstrate that RJ and its related substances extended the life span in C. elegans, suggesting that RJ may contain longevity-promoting factors common to diverse species across phyla. pRJ-Fr. 5 had higher life span-extending activity than either RJ or pRJ and extended the life span in part through the IIS-DAF-16 pathway. We provide the first evidence that 10-HDA, a defined natural product in RJ, extended organismal lifespan. It is noteworthy that 10-HDA performed its lifespan-extending function through a mechanism totally different from the IIS-DAF-16 pathway. Further search and characterization of the lifespan-extending agents in RJ and pRJ may broaden our understanding of the gene network of longevity regulation in diverse species and provide the possibility for nutraceutical interventions in the aging process. C. elegans N2 hermaphrodites were untreated or treated with pRJ-Fr. 5 (25mg/ml) for 24 h starting at the larval 4 (L4) stage.
2011-07-21 | E-GEOD-26094 | biostudies-arrayexpress
Project description:One of the most important issues in the study of aging is to discover compounds with longevity-promoting activity and to unravel their underlying mechanisms. Queen honey bees are continuously fed royal jelly (RJ), and they live more than 10 times longer than hive workers, derived from the same diploid genome, which are fed it only for a short period of time during their larval stages. Therefore, RJ is likely to contain longevity-promoting agents for queens. RJ has been reported to possess diverse pharmacological properties. Furthermore, protease-treated RJ (pRJ) has additional beneficial activities. How RJ and pRJ exert these effects and which components in them play a critical role is largely unknown. The evolutionally conserved mechanisms that control lifespan have been indicated. The nematode Caenorhabditis elegans has been widely used for study of aging and longevity, due to its relatively short lifespan and well-established genetic pathways. The purpose of the present study was to elucidate whether RJ and its related substances contain the life span-extending activity in C. elegans and to obtain some insight into the active agents and their mechanisms. We found that both RJ and pRJ extended the lifespan of C. elegans. The life span-extending activity of pRJ was enriched by ODS column chromatography (pRJ-Fraction 5). pRJ-Fr. 5 extended the life span partly by acting through the FOXO transcription factor DAF-16, the activation of which is known to promote longevity in C. elegans by reducing insulin/IGF-1 signaling (IIS). pRJ-Fr. 5 induced changes in the expression of 3 genes encoding insulin-like peptides. Moreover, pRJ-Fr. 5 and reduced IIS shared some common features in terms of their effect on gene expression, such as up-regulation of dod-3 and down-regulation of dod-19, dao-4 and fkb-4. The dod-19 is a previously identified life span determinant in C. elegans, and the fkb-4 encodes a homologue of the mammalian FK506-binding protein. 10-Hydroxy-2-decenoic acid (10-HDA), which was present in high concentration in pRJ-Fr. 5, increased the lifespan independently of DAF-16 activity.These results demonstrate that RJ and its related substances extended the life span in C. elegans, suggesting that RJ may contain longevity-promoting factors common to diverse species across phyla. pRJ-Fr. 5 had higher life span-extending activity than either RJ or pRJ and extended the life span in part through the IIS-DAF-16 pathway. We provide the first evidence that 10-HDA, a defined natural product in RJ, extended organismal lifespan. It is noteworthy that 10-HDA performed its lifespan-extending function through a mechanism totally different from the IIS-DAF-16 pathway. Further search and characterization of the lifespan-extending agents in RJ and pRJ may broaden our understanding of the gene network of longevity regulation in diverse species and provide the possibility for nutraceutical interventions in the aging process.
2011-07-22 | GSE26094 | GEO
Project description:Increasing age is a risk factor for many diseases; therefore developing pharmacological interventions that slow down ageing and consequently postpone the onset of many age-related diseases is highly desirable. In this work we analyse data from the DrugAge database, which contains chemical compounds and their effect on the lifespan of model organisms. Predictive models were built using the machine learning method random forests to predict whether or not a chemical compound will increase Caenorhabditis elegans' lifespan, using as features Gene Ontology (GO) terms annotated for proteins targeted by the compounds and chemical descriptors calculated from each compound's chemical structure. The model with the best predictive accuracy used both biological and chemical features, achieving a prediction accuracy of 80%. The top 20 most important GO terms include those related to mitochondrial processes, to enzymatic and immunological processes, and terms related to metabolic and transport processes. We applied our best model to predict compounds which are more likely to increase C. elegans' lifespan in the DGIdb database, where the effect of the compounds on an organism's lifespan is unknown. The top hit compounds can be broadly divided into four groups: compounds affecting mitochondria, compounds for cancer treatment, anti-inflammatories, and compounds for gonadotropin-releasing hormone therapies.
| S-EPMC5559171 | biostudies-literature
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