Polyamine metabolite spermidine rejuvenates the oocyte quality by enhancing mitophagy during female reproductive aging
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ABSTRACT:
PROVIDER: PRJNA999685 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25454142_1.fastq.gz | Fastqsanger.gz | |||
| SRR25454142_2.fastq.gz | Fastqsanger.gz | |||
| SRR25454143_1.fastq.gz | Fastqsanger.gz | |||
| SRR25454143_2.fastq.gz | Fastqsanger.gz | |||
| SRR25454144_1.fastq.gz | Fastqsanger.gz |
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Project description:Advanced age is a primary risk factor for female infertility due to reduced ovarian reserve and declining oocyte quality. However, as an important contributing factor, the role of metabolic regulation during reproductive aging is poorly understood. Here, we applied untargeted metabolomics to identify spermidine as a critical metabolite in ovaries to protect oocytes against aging. In particular, we found that spermidine level was reduced in aged ovaries and supplementation of spermidine promoted follicle development, oocyte maturation, early embryonic development and female fertility of aged mice. By micro-transcriptomic analysis, we further discovered that recovery of oocyte quality by spermidine was mediated by enhancement of mitophagy activity and mitochondrial function in aged mice, and this action mechanism was conserved in porcine oocytes under oxidative stress. Altogether, our findings demonstrate that spermidine supplementation is a potentially effective strategy to ameliorate oocyte quality and reproductive outcome of women at an advanced age.
2023-11-10 | GSE239551 | GEO
Project description:Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends lifespan, while it exerts cardioprotective effects through reduction of cardiac hypertrophy and preservation of diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy, mitochondrial respiration and mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine failed to promote cardioprotection in mice lacking the autophagy-related gene Atg5 in cardiomyocytes. In Dahl salt-sensitive rats fed high-salt diet, a model for hypertension-induced congestive heart failure, spermidine reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. Finally, high dietary spermidine intake correlated with reduced blood pressure and a lower incidence of cardiovascular disease in humans. Our results suggest a novel and generic strategy against cardiovascular disease.
2016-11-13 | GSE86882 | GEO
Project description:Polyamines are aliphatic polycations that have emerged as important determinants of cell growth and viability in rapidly proliferating cells, including in the pathogenic protozoan parasite Leishmania donovani. In L. donovani, the polyamine spermidine is synthesized by the successive conversion of ornithine into putrescine (catalyzed by ornithine decarboxylase or ODC) and putrescine into spermidine (catalyzed by spermidine synthase or SPDSYN). Deletion of either ODC (del-odc) or SPDSYN (del-spdsyn) from the L. donovani genome renders these parasites auxotrophic for polyamines and these mutants are impaired in their ability to survive both in culture and within the mammalian host without the addition of exogenous polyamine supplementation. Significantly, del-odc parasites immediately cease proliferation after putrescine is removed from the culture media and perish within two weeks, while spermidine starved del-spdsyn mutants, which retain intracellular putrescine pools, show a slow-growth phenotype, and persist for several weeks in culture. To elucidate the key differences within the proteome of putrescine-starved del-odc cells and spermidine-starved del-spdsyn parasites, a shotgun quantitative proteomics approach was undertaken using TMT labeling and LC-MS/MS analysis. Briefly, three biological replicates each for mid-log phase del-odc and del-spdsyn promastigotes grown in the presence of exogenous putrescine (for del-odc) or spermidine (for del-spdsyn) supplementation were washed to remove the exogenous polyamine supplementation and incubated in polyamine-free media. At 24 and 48 h, cells from each biological replicate were isolated and prepared for tandem mass tag (TMT) labeling and downstream LC-MS/MS analyses. Peptides were identified using a database generated from the reference genome of L. donovani BPK282A1 strain. Changes in relative protein abundance for the polyamine-starved del-odc and del-spdsyn cell lines at 24 and 48 h were calculated by comparing aggregate total reporter ion intensities for each protein to that of the corresponding polyamine-supplemented 0-h timepoint.
2022-08-29 | PXD036349 | Pride
Project description:To compare the effects of spermidine, key polyamine, on the gene expression profile of organ cultured human hair follicles Vehicle treated Vs. 0.5 µM spermidine treatment. Two control samples, two spermidine treated samples
2011-04-16 | E-GEOD-28650 | biostudies-arrayexpress
Project description:Administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extends the lifespan of various model organisms including yeast, flies and worms. In ageing yeast, spermidine treatment triggeres epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), leading to induction of autophagy and thereby suppressing oxidative stress and necrosis. In order to further characterize the effects by spermidine supplementation of aging yeast cultures and to understand how global histone deacetylation affects gene transcription during aging, Affymetrix-based microarray analyses of three day old as well as ten day old cultures with and without administration of spermidine was performed.
2012-01-04 | E-MTAB-912 | biostudies-arrayexpress
Project description:The naturally occurring polyamines putrescine, spermidine or spermine are ubiquitous in all cells. Although polyamines have prominent regulatory roles in cell division and growth, precise molecular and cellular functions are not well established in vivo. In this work we have performed a microarray experiment in a polyamine mutant (delta-spe3 delta-fms1) strain to investigate the responsiveness of yeast genes to supplementation with spermidine and spermine. Expression analysis identified genes responsive to the addition of either excess spermidine (10-5 M) or spermine (10-5 M) compared to a control culture containing 10-8 M spermidine. 247 genes were up-regulated >2-fold, and 11 genes were up-regulated more than 10-fold after spermidine addition. Functional categorization of the genes showed induction of transport related genes, and genes involved in methionine, arginine, lysine, NAD and biotin biosynthesis. 268 genes were down-regulated more than 2-fold, and 6 genes were down-regulated more than 8-fold after spermidine addition. A majority of the down-regulated genes are involved in nucleic acid metabolism and various stress responses. In contrast, only few genes (18) were significantly responsive to spermine. Thus, results from global gene expression profiling demonstrate a more major role for spermidine in modulating gene expression in yeast than spermine.
2009-08-20 | GSE15269 | GEO
Project description:Polyamines are absolutely required for cell growth and proliferation. While polyamine depletion results in reversible cell cycle arrest, the actual mechanism of growth inhibition is still obscure. This experiment aimed at determining the cellular processes elicited by re-addition of polyamines to polyamine-depleted (growth arrested) cells. In order to reveal the general transcriptional responses to polyamine re-addition, NIH3T3 mouse fibroblasts were first treated with 1mM L-Difluoromethylornithine (DFMO) for 96 hours and then growth stimulated by spermidine. Cells were collected at 0, 30, 60, 120, 240, 360, 480 and 600 min upon addition of spermidine to polyamine-depleted (growth arrested) cells. Total RNA was isolated, reverse-transcribed, fragmented, labeled and hybridized to Affymetrix MoGene 1.0 ST DNA array.
2012-09-11 | E-GEOD-36664 | biostudies-arrayexpress
Project description:To compare the effects of spermidine, key polyamine, on the gene expression profile of organ cultured human hair follicles
2011-04-16 | GSE28650 | GEO
Project description:Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health 1. The natural polyamine spermidine has been linked to autophagy regulation, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders 2. Here, we report that spermidine levels increase upon acute fasting in yeast, flies, mice and healthy humans. Genetic or pharmacological blockade of endogenous spermidine synthesis reduced fasting-induced autophagy in yeast, worms and human cells. Furthermore, perturbing the polyamine pathway in vivo abrogated the lifespan-extending, cardioprotective and antiarthritic effects of intermittent fasting. Mechanistically, spermidine mediated these effects via hypusination of the autophagy regulator eIF5A. In sum, the polyamine-hypusination axis thus emerges as a bona fide and phylogenetically conserved metabolic control hub for longevity and autophagy induction.
2024-04-30 | PXD035909 | Pride
Project description:Study is aimed to understand translation regulation of mRNA in low and high polyamines in S. cerevisiae. mRNA seq and Ribosome profiling were performed in yeast cells, in duplicates, under low (0 spermidine) and high (10 µM) spermidine. Translation efficiency was calculated (low vs high SPD) and GO analysis reveals 23 transporters as the only class undergo TE downregulation in high SPD condition. Further, we investigated role of these 23 transporters in polyamine transport and identified HOL1 as the high affinity polyamine transporter. This study further show that HOL1 is under polyamine control of translation regulation through conserved fungal uORF MLLLPS*.
2021-08-09 | GSE171392 | GEO