The time course of microRNA transcriptomes during C. elegans ageing
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE136612 | GEO | 2019/09/03
REPOSITORIES: GEO
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Project description:Increased protein misfolding and aggregation are key hallmarks of ageing and many age-related diseases. As generating and maintaining a functional proteome (proteostasis) is crucial to every cellular process, this age-related decline in proteostasis is suggested to play a primary role in the breakdown of diverse cellular subsystems during ageing. Indeed, augmented proteostasis pathways are associated with extended lifespan across different species. With the ribosome as the earliest proteostasis checkpoint, decreased protein synthesis is also a conserved mechanism that extends lifespan. Yet, it remains unclear whether ageing impacts translation after initiation. Here, we use worms and yeast to investigate how ageing influences translation elongation. We show an age-dependent increase in ribosome pausing at diverse positions in coding sequences. This pausing is conserved in both worms and yeast, particularly at Arg and polybasic regions. We further show that such pausing is associated with the age-dependent aggregation of truncated nascent proteins involved in proteostasis pathways, notably aminoacyl tRNA synthetases. Moreover, we find that impairment in clearing truncated nascent proteins is associated with decreased lifespan. These data establish elongation kinetics and co-translational quality control as critical contributors of the age-related proteostasis collapse, which may precipitate the systemic decline observed during ageing.
2021-11-09 | GSE152850 | GEO
Project description:The plasticity of ageing suggests that longevity may be controlled epigenetically by specific alterations in chromatin state. The link between chromatin and ageing has mostly focused on histone deacetylation by the Sir2 family1, 2, but less is known about the role of other histone modifications in longevity. Histone methylation has a crucial role in development and in maintaining stem cell pluripotency in mammals3. Regulators of histone methylation have been associated with ageing in worms4, 5, 6, 7 and flies8, but characterization of their role and mechanism of action has been limited. Here we identify the ASH-2 trithorax complex9, which trimethylates histone H3 at lysine 4 (H3K4), as a regulator of lifespan in Caenorhabditis elegans in a directed RNA interference (RNAi) screen in fertile worms. Deficiencies in members of the ASH-2 complex—ASH-2 itself, WDR-5 and the H3K4 methyltransferase SET-2—extend worm lifespan. Conversely, the H3K4 demethylase RBR-2 is required for normal lifespan, consistent with the idea that an excess of H3K4 trimethylation—a mark associated with active chromatin—is detrimental for longevity. Lifespan extension induced by ASH-2 complex deficiency requires the presence of an intact adult germline and the continuous production of mature eggs. ASH-2 and RBR-2 act in the germline, at least in part, to regulate lifespan and to control a set of genes involved in lifespan determination. These results indicate that the longevity of the soma is regulated by an H3K4 methyltransferase/demethylase complex acting in the C. elegans germline. There are 23 samples in total. ASH-2 knock-down increases lifespan in a germline dependent manner. We examined ASH-2 regulated genes that are dependent on the presence of an intact germline using WT or glp-1(e2141ts) mutant worms which develop only 5-15 meiotic germ cells treated with either empty vector (EV) or ash-2 RNAi. We examined gene expression at the L3 stage (when we observe changes in H3K4me3) and at a mid life stage (day 8). The majority of ASH-2 controlled genes were regulated in a germline dependent manner. Samples were collected in triplicate for each condition (but Day 8 N2 (WT) E.V. #3 was excluded from all analysis due to quality issues).
2011-07-08 | E-GEOD-30505 | biostudies-arrayexpress
Project description:The nematode Caenorhabditis elegans was treated with extracts of the Traditional Chinese Medicine plants Cuscuta chinensis and Eucommia ulmoides from the L4 stage. In aged worms (on the 7th and 12th day of adulthood) different health parameters were determined. Besides the prolongation of lifespan, we found that C. chinensis improved the swimming behavior, pharyngeal pumping rate, stress resistance, mechanosensation and memory of aged C. elegans. Furthermore, the extract treatment reduced the autofluorescence, which is a known biomarker of ageing. Thus, we concluded that C. chinensis is an overall healthspan enhancer. In contrast, the E. ulmoides extract specifically enhanced the lifespan and stress resistance of aged C. elegans, but did not improve any other health aspect. To reveal the mechanism behind the healthspan enhancing effects of C. chinensis, the transcriptome of treated and untreated C. elegans on the 12th day of adulthood was analysed. For comparison purposes, E. ulmoides treated nematodes were included in the analysis.
2024-10-30 | GSE274478 | GEO
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:Background: We here show that inhibitors of mitochondrial complex I promote physical activity, stress resistance as well as lifespan of Caenorhabditis elegans despite normal food uptake, i.e. in the absence of DR. Dietary restriction (DR) extends lifespan and promotes metabolic health in evolutionary distinct species. The RNA-seq data comprises 4 age groups (1, 5, 10 and 20 days after L4) and 2 different conditions (rotenone and normal feeding (DMSO)) 22 samples: mRNA profiles of 1-day, 5-day and 10-day old worms as triplicates for each, rotenone and solvent control treatment; mRNA profiles of 20-day old worms as duplicates for each, rotenone and solvent control treatment
2013-04-16 | E-GEOD-46051 | biostudies-arrayexpress
Project description:Removal of the 5’ cap of mRNAs (decapping) is mainly catalyzed by a conserved holoenzyme, composed of the catalytic subunit DCP2 and its essential cofactor DCP1. Studies in C. elegans have shown that ageing is characterized by the accumulation of decapping factors in P-Bodies, and loss of DCAP-1/DCP1 or DCAP-2/DCP2 significantly shortens lifespan. However, the relationship between mRNA decapping and ageing remains elusive. Here we present a comparative microarray study that aims to uncover this link by identifying differentially expressed genes between wild type mid-aged worms (9 days old) and age-matched animals with reduced function of DCAP-1/DCP1.
2023-01-20 | GSE199807 | GEO
Project description:The time course of microRNA transcriptomes during C. elegans ageing
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Project description:The determination of molecular pathways that are affected with age and lead to increased disease susceptibility is crucial. The nematode has proven an ideal experimental model to study ageing due to significantly conserved genes governing ageing throughout species. Profiling of gene expression levels in ageing wt Caenorhabditis elegans, utilizing a robust Affymetrix microarray platform, resulted in the identification of age-dependent gene expression alterations that characterize the nematode's ageing process. We used Affymetrix microarrays to detail the global programme of gene expression underlying ageing and identified distinct classes of up- or down-regulated genes during this process.
2023-12-14 | GSE163253 | GEO
Project description:Metabolic diseases are strongly associated with endoplasmic reticulum (ER) stress. Upon ER stress, the unfolded protein response (UPR) is activated to limit cellular damage. However, escalating cellular UPR response weakens with age. Here, we show that 5-day-old Caenorhabditis elegans fed a bacteria diet with 2% glucose (high glucose diet, HGD-5) extend their lifespan while shortening the lifespan of 1-day-old (HGD-1) animals. We observed a metabolic shift in HGD-1 as glucose and fertility synergistically prolonged the lifespan of HGD-5, independently of DAF-16. Notably, we identified that UPR stress sensors ATF-6 and PEK-1 extended the longevity of HGD-5 worms, while the ire-1 ablation drastically increased HGD-1 lifespan. Based on these observations, we postulate that HGD activates the otherwise quiescent UPR in aged worms to overcome ageing-related stress and restore ER homeostasis. In contrast, young animals subjected to HGD provokes unresolved ER stress, conversely leading to a detrimental stress response.
2021-08-31 | GSE182981 | GEO
Project description:We presents a complete single-cell atlas of aging worms, encompassing both somatic and germ cell types. This atlas was built upon 241K nuclei across the worm lifespan at day 1, 6, 12, and 14 (100%, 99%, 61%, and 14% survival rates, respectively). The worms were aged under normal physiological conditions, without interfering with their reproductive processes.
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