RNA sequencing of mouse hepatic response to lifespan-extending interventions
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA544682 | ENA |
REPOSITORIES: ENA
Similar Datasets
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: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: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:RNA sequencing of mouse hepatic response to compounds with predicted lifespan-extending effect
| PRJNA545143 | ENA
Project description:Lithocholic acid significantly extends the lifespan in Drosophila melanogaster by targeting multiple lifespan-extending pathways
| PRJNA433535 | 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:This dataset consists of kidney gene expression profiles of young UM-HET3 mice subjected to rilmenidine for 1 month. Corresponding age-, sex- and strain-matched littermate controls are also presented. Using this data, we assessed association between gene expression response to rilmenidine in kidney and established signatures of lifespan-extending interventions and aging. This dataset complements corresponding liver data stored at GSE131868.
2022-09-30 | GSE206982 | GEO
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: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:Dietary, genetic and pharmacological interventions can extend health- and lifespan in diverse model organisms whilst delaying the onset of age-related pathologies. In the context of the brain, several of these interventions have shown to improve molecular, structural and cognitive hallmarks of brain aging. However, there is limited quantitative knowledge on where in the brain these interventions are most active and to what degree their molecular mechanisms overlap. Here we performed region-resolved RNA-seq of the brain of aged mice either subjected to acute dietary restriction (aDR), injection of young mouse plasma (YMP), as well as their corresponding controls (ad libitium feeding and PBS injection, respectively). This encompasses 229 samples dissected from 15 regions. We reveal that each rejuvenation intervention impacts gene expression in a region-dependent manner, varying in timing, magnitude and biological function.
2023-04-17 | GSE227689 | GEO