Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Rapamycin reduces Drosophila longevity under low nutrition.

ABSTRACT: Rapamycin treatment is considered a pharmacological intervention with the potential to mimic the longevity benefits of dietary manipulations. However, how rapamycin interacts with nutrition is not fully understood. Here we studied the effect of rapamycin on the longevity of Drosophila under a range of dietary conditions. In diets low in nutrients, rapamycin reduced longevity in a dosage-dependent manner. This dosage effect requires some nutrients as rapamycin has no impact on survival under starvation conditions. Under a balanced diet of yeast and sugar, rapamycin had no repeatable beneficial effect on organismal longevity. These results show that the effect of rapamycin on longevity is sensitive to the nutritional environment and it can reduce lifespan when nutrients are limited.

SUBMITTER: Villa-Cuesta E

PROVIDER: S-EPMC5458632 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Rapamycin reduces <i>Drosophila</i> longevity under low nutrition.

Villa-Cuesta Eugenia E Fan Frances F Rand David M DM

IOSR journal of pharmacy 20140801 8

Rapamycin treatment is considered a pharmacological intervention with the potential to mimic the longevity benefits of dietary manipulations. However, how rapamycin interacts with nutrition is not fully understood. Here we studied the effect of rapamycin on the longevity of Drosophila under a range of dietary conditions. In diets low in nutrients, rapamycin reduced longevity in a dosage-dependent manner. This dosage effect requires some nutrients as rapamycin has no impact on survival under star ...[more]

PMID: 28593179

Similar Datasets

Longevity, aging and rapamycin.

Project description:The federal drug administration (FDA)-approved compound rapamycin was the first pharmacological agent shown to extend maximal lifespan in both genders in a mammalian species. A major question then is whether the drug slows mammalian aging or if it has isolated effects on longevity by suppressing cancers, the main cause of death in many mouse strains. Here, we review what is currently known about the effects that pharmacological or genetic mammalian target of rapamycin (mTOR) inhibition have on mammalian aging and longevity. Currently available evidence seems to best fit a model, wherein rapamycin extends lifespan by suppressing cancers. In addition the drug has symptomatic effects on some aging traits, such as age-related cognitive impairments.

| S-EPMC4207939 | biostudies-literature

RPD3 histone deacetylase and nutrition have distinct but interacting effects on Drosophila longevity.

Project description:Single-gene mutations that extend longevity have revealed regulatory pathways related to aging and longevity. RPD3 is a conserved histone deacetylase (Class I HDAC). Previously we showed that Drosophila rpd3 mutations increase longevity. Here we tested the longevity effects of RPD3 on multiple nutrient levels. Dietary restriction (DR) has additive effects on RPD3-mediated longevity extension, but the effect may be modestly attenuated relative to controls. RPD3 and DR therefore appear to operate by distinct but interacting mechanisms. Since RPD3 regulates transcription, the mRNA levels for two proteins involved in nutrient signaling, 4E-BP and Tor, were examined in rpd3 mutant flies. 4E-BP mRNA was reduced under longevity-increasing conditions. Epistasis between RPD3 and 4E-BP with regard to longevity was then tested. Flies only heterozygous for a mutation in Thor, the 4E-BP gene, have modestly decreased life spans. Flies mutant for both rpd3 and Thor show a superposition of a large RPD3-mediated increase and a small Thor-mediated decrease in longevity at all food levels, consistent with each gene product having distinct effects on life span. However, DR-mediated extension was absent in males carrying both mutations and lessened in females. Our results support the view that multiple discrete but interacting mechanisms regulate longevity.

| S-EPMC4712336 | biostudies-literature

Rapamycin reduces neuronal mutant huntingtin aggregation and ameliorates locomotor performance in <i>Drosophila</i>.

Project description:Huntington's disease (HD) is a neurodegenerative disease characterized by movement and cognitive dysfunction. HD is caused by a CAG expansion in exon 1 of the HTT gene that leads to a polyglutamine (PQ) repeat in the huntingtin protein, which aggregates in the brain and periphery. Previously, we used Drosophila models to determine that Htt-PQ aggregation in the heart causes shortened lifespan and cardiac dysfunction that is ameliorated by promoting chaperonin function or reducing oxidative stress. Here, we further study the role of neuronal mutant huntingtin and how it affects peripheral function. We overexpressed normal (Htt-PQ25) or expanded mutant (Htt-PQ72) exon 1 of huntingtin in Drosophila neurons and found that mutant huntingtin caused age-dependent Htt-PQ aggregation in the brain and could cause a loss of synapsin. To determine if this neuronal dysfunction led to peripheral dysfunction, we performed a negative geotaxis assay to measure locomotor performance and found that neuronal mutant huntingtin caused an age-dependent decrease in locomotor performance. Next, we found that rapamycin reduced Htt-PQ aggregation in the brain. These results demonstrate the role of neuronal Htt-PQ in dysfunction in models of HD, suggest that brain-periphery crosstalk could be important to the pathogenesis of HD, and show that rapamycin reduces mutant huntingtin aggregation in the brain.

| S-EPMC10562706 | biostudies-literature

Visible light reduces C. elegans longevity.

Project description:The transparent nematode Caenorhabditis elegans can sense UV and blue-violet light to alter behavior. Because high-dose UV and blue-violet light are not a common feature outside of the laboratory setting, we asked what role, if any, could low-intensity visible light play in C. elegans physiology and longevity. Here, we show that C. elegans lifespan is inversely correlated to the time worms were exposed to visible light. While circadian control, lite-1 and tax-2 do not contribute to the lifespan reduction, we demonstrate that visible light creates photooxidative stress along with a general unfolded-protein response that decreases the lifespan. Finally, we find that long-lived mutants are more resistant to light stress, as well as wild-type worms supplemented pharmacologically with antioxidants. This study reveals that transparent nematodes are sensitive to visible light radiation and highlights the need to standardize methods for controlling the unrecognized biased effect of light during lifespan studies in laboratory conditions.

| S-EPMC5834526 | biostudies-literature

Cold hardening improves larval tick questing under low temperatures at the expense of longevity.

Project description:Questing in ticks is essential for locating a host, and this behavioral response can occur at regionally specific low temperatures for most tick species. Little is known about the dynamics between tick questing behavior and temperature in ticks, specifically how this may impact other aspects of tick biology. Here, we examine whether cold hardening increases questing in three larval tick species (Ixodes uriae, Dermacentor variabilis, and Amblyomma americanum) at low temperatures and whether cold hardening impacts longevity. Rapid cold hardening and prolonged cold acclimation benefitted ticks by decreasing the temperature of chill coma onset, and increased survival, activity, and questing in ticks at low temperatures. Oxygen consumption increased at low temperatures following acclimation in larvae, suggesting this process has a distinct metabolic expense. This increased metabolism associated with hardening led to a substantial reduction in larval longevity as nutrient reserves are limited and cannot be replenished until a host is located. These studies suggest that tick larvae, and likely other developmental stages, require a delicate balance between the need for questing at low temperatures and survival until the first blood meal.

| S-EPMC9936387 | biostudies-literature

Early-life exposure to low-dose oxidants can increase longevity via microbiome remodelling in Drosophila.

Project description:Environmental stresses experienced during development exert many long-term effects upon health and disease. For example, chemical oxidants or genetic perturbations that induce low levels of reactive oxygen species can extend lifespan in several species. In some cases, the beneficial effects of low-dose oxidants are attributed to adaptive protective mechanisms such as mitohormesis, which involve long-term increases in the expression of stress response genes. Here we show in Drosophila that transient exposure to low concentrations of oxidants during development leads to an extension of adult lifespan. Surprisingly, this depends upon oxidants acting in an antibiotic-like manner to selectively deplete the microbiome of Acetobacter proteobacteria. We demonstrate that the presence of Acetobacter species, such as A. aceti, in the indigenous microbiota increases age-related gut dysfunction and shortens lifespan. This study demonstrates that low-dose oxidant exposure during early life can extend lifespan via microbiome remodelling rather than mitohormesis.

| S-EPMC5841413 | biostudies-literature

Nectarine promotes longevity in Drosophila melanogaster.

Project description:Fruits containing high antioxidant capacities and other bioactivities are ideal for promoting longevity and health span. However, few fruits are known to improve the survival and health span in animals, let alone the underlying mechanisms. Here we investigate the effects of nectarine, a globally consumed fruit, on life span and health span in Drosophila melanogaster. Wild-type flies were fed standard, dietary restriction (DR), or high-fat diet supplemented with 0-4% nectarine extract. We measured life span, food intake, locomotor activity, fecundity, gene expression changes, and oxidative damage indicated by the level of 4-hydroxynonenal-protein adduct in these flies. We also measured life span, locomotor activity, and oxidative damage in sod1 mutant flies on the standard diet supplemented with 0-4% nectarine. Supplementation with 4% nectarine extended life span, increased fecundity, and decreased expression of some metabolic genes, including a key gluconeogenesis gene, PEPCK, and oxidative stress-response genes, including peroxiredoxins, in female wild-type flies fed the standard, DR, or high-fat diet. Nectarine reduced oxidative damage in wild-type females fed the high-fat diet. Moreover, nectarine improved the survival of and reduced oxidative damage in female sod1 mutant flies. Together, these findings suggest that nectarine promotes longevity and health span partly by modulating glucose metabolism and reducing oxidative damage.

| S-EPMC3090488 | biostudies-literature

Redox-proteomes of human NOS1-transduced versus MOCK SH-SY5Y neuroblastoma cells under full nutrition, serum-free starvation, and rapamycin treatment.

Project description:Upregulations of neuronal nitric oxide synthase (nNOS/NOS1) in the mouse brain upon aging and stress suggest a role of NO-dependent redox protein modifications for age-associated protein imbalances or dysfunctions. We generated a cell model, in which constitutive expression of nNOS in SH-SY5Y cells at a level comparable with mouse brain replicates the aging phenotype, that is, slowing of cell proliferation, cell enlargement, and expression of senescence markers. nNOS+ and MOCK cells were exposed to proteostasis stress by the treatment with rapamycin or serum-free starvation versus control conditions. To analyze NO-mediated S-nitrosylations (SNO) and other reversible protein modifications including disulfides and sulfoxides, we used complimentary proteomic approaches encompassing 2D-SNO-DIGE (differential gel electrophoresis), SNO-site identification (SNOSID), SNO Super-SILAC, SNO BIAM-Switch, and Redox-BIAM switch. The redox proteomes were analyzed using hybrid liquid chromatography/mass spectrometry (LC/MS). Full scan MS-data were acquired using Xcalibur, and raw mass spectra were analyzed using the proteomics software MaxQuant. The human reference proteome sets from uniprot were used as templates to identify peptides and proteins and quantify protein expression. The DiB data file contains MaxQuant output tables of the redox-modified proteins.The tables include peptide and protein identification, accession numbers, protein, and gene names, sequence coverage and quantification values of each sample. Differences in protein redox modifications in MOCK versus nNOS+ SH-SY5Y cells and interpretation of results are presented in (Valek et al., 2018).

| S-EPMC6230977 | biostudies-literature

Evolution of longevity improves immunity in Drosophila.

Project description:Much has been learned about the genetics of aging from studies in model organisms, but still little is known about naturally occurring alleles that contribute to variation in longevity. For example, analysis of mutants and transgenes has identified insulin signaling as a major regulator of longevity, yet whether standing variation in this pathway underlies microevolutionary changes in lifespan and correlated fitness traits remains largely unclear. Here, we have analyzed the genomes of a set of Drosophila melanogaster lines that have been maintained under direct selection for postponed reproduction and indirect selection for longevity, relative to unselected control lines, for over 35 years. We identified many candidate loci shaped by selection for longevity and late-life fertility, but - contrary to expectation - we did not find overrepresentation of canonical longevity genes. Instead, we found an enrichment of immunity genes, particularly in the Toll pathway, suggesting that evolutionary changes in immune function might underpin - in part - the evolution of late-life fertility and longevity. To test whether this genomic signature is causative, we performed functional experiments. In contrast to control flies, long-lived flies tended to downregulate the expression of antimicrobial peptides upon infection with age yet survived fungal, bacterial, and viral infections significantly better, consistent with alleviated immunosenescence. To examine whether genes of the Toll pathway directly affect longevity, we employed conditional knockdown using in vivo RNAi. In adults, RNAi against the Toll receptor extended lifespan, whereas silencing the pathway antagonist cactus--causing immune hyperactivation - dramatically shortened lifespan. Together, our results suggest that genetic changes in the age-dependent regulation of immune homeostasis might contribute to the evolution of longer life.

| S-EPMC6292704 | biostudies-literature

Deep proteome of human nNOS/NOS1-positive versus MOCK SH-SY5Y neuroblastoma cells under full nutrition, serum free starvation and rapamycin treatment.

Project description:Upregulations of neuronal nitric oxide synthase (nNOS/NOS1) in the mouse brain upon aging suggest a role in age-associated changes of protein homeostasis. We generated a cell model, in which constitutive expression of nNOS in SH-SY5Y cells at a level comparable to mouse brain replicates the aging phenotype i.e. slowing of cell proliferation, cell enlargement and expression of senescence markers. nNOS+ and MOCK cells were exposed to proteostasis stress by treatment with rapamycin or serum-free starvation. The proteomes were analyzed per SILAC or label-free using hybrid liquid chromatography/mass spectrometry (LC/MS). Full scan MS-data were acquired using Xcalibur, and raw mass spectra were analyzed using the proteomics software MaxQuant. The human reference proteome from uniprot was used as template to identify peptides and proteins and quantify protein expression. The DiB data file contains essential MaxQuant output tables and includes peptide and protein identification, accession numbers, protein and gene names, sequence coverage and quantification values of each sample. Differences in protein expression in MOCK versus nNOS+ SH-SY5Y cells and interpretation of results are presented in Valek et al. (2018). Raw mass spectra and MaxQuant output files have been deposited to the ProteomeXchange Consortium (Vizcaino et al., 2014) via the PRIDE partner repository with the dataset identifier PRIDE: PXD010538.

| S-EPMC6231036 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data