RNA-seq profiling of C.elegans treated with bromhexine and genipin
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE329138 | GEO | 2026/07/31
REPOSITORIES: GEO
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Project description:Pharmacological interventions directly modulating ageing would extend human healthspan, resulting in dramatic medical and economic benefits. Such interventions should be efficacious in adults and ideally repurpose drugs known to be safe. Here we show that dramatic lifespan extension can be achieved by targeting multiple, evolutionarily conserved ageing pathways using drugs already used in humans. Using this approach in C. elegans, we were able to slow ageing, improve healthspan and minimize trade-offs. We show that daf-2, daf-7 and sbp-1 (mammalian SREBP-1c) interact upstream of changes in lipid metabolism, resulting in increased monounsaturated fatty acid content and lifespan extension. For one combination, we observed evolutionary conservation in fruit flies. To the best of our knowledge, this is the largest lifespan effect ever reported for any adult-onset drug treatment in C. elegans. Drug repurposing approaches, by leveraging drugs already approved for humans, could lead to rapid translation of experimental results to clinical applications.
2018-12-17 | GSE108263 | GEO
Project description:Transcriptome-based drug screening is emerging as a powerful tool to identify geroprotective compounds to intervene in age-related disease. We hypothesized that, by mimicking the transcriptional signature of the highly conserved longevity intervention of FOXO3 (daf-16 in worms) overexpression, we could identify and repurpose compounds with similar downstream effects to increase longevity. Our in silico screen, utilizing the LINCS transcriptome database of genetic and compound interventions, identified several FDA-approved compounds that activate FOXO downstream targets in mammalian cells. These included the neuromuscular blocker atracurium, which also robustly extends both lifespan and healthspan in C. elegans. This longevity is dependent on both daf-16 signaling and inhibition of the neuromuscular acetylcholine receptor. Other neuromuscular blockers tubocurarine and pancuronium caused similar healthspan benefits. Together, these data demonstrate the capacity to mimic genetic lifespan interventions with drugs, and in doing so, reveal that the neuromuscular acetylcholine receptor regulates the highly conserved FOXO/DAF-16 longevity pathway.
2021-07-06 | GSE149944 | GEO
Project description:Hydrogen sulfide (H2S) is formed naturally from L-cysteine in a variety of mammalian and non-mammalian cells. To date, numerous biological effects have been ascribed to H2S including control of cardiovascular, immune and nervous function. Over or under production of H2S has been observed in several disease states including hypertension and inflammation. In addition, it has been stipulated that H2S may affect the ageing process. The model nematode Caenorhabditis elegans is ideally suited for assessing drug effects on lifespan since it is relatively short-lived, can be easily exposed to drugs and its genome is fully sequenced and widely annotated.
2013-07-30 | GSE16975 | GEO
Project description:Hydrogen sulfide (H2S) is formed naturally from L-cysteine in a variety of mammalian and non-mammalian cells. To date, numerous biological effects have been ascribed to H2S including control of cardiovascular, immune and nervous function. Over or under production of H2S has been observed in several disease states including hypertension and inflammation. In addition, it has been stipulated that H2S may affect the ageing process. The model nematode Caenorhabditis elegans is ideally suited for assessing drug effects on lifespan since it is relatively short-lived, can be easily exposed to drugs and its genome is fully sequenced and widely annotated. The global transcriptome of control nematodes (raised using standardized laboratory conditions) was compared to nematodes exposed to 100 uM GYY4137 (morpholin-4-ium 4 methoxyphenyl(morpholino) phosphinodithioate), a slow releasing H2S donor drug.
2013-07-30 | E-GEOD-16975 | biostudies-arrayexpress
Project description:Various anti-aging interventions exhibit potential in extending lifespan, yet most of these interventions are inefficacy or even have deleterious effects on healthspan. Ginkgolide B (GB) is a Ginkgo biloba-derived small molecule that reduces aging-related morbidities; however, the effects of GB on healthspan and longevity remain elusive. Here, we report that continuous oral GB administration in mice starting at 20 months extended their lifespan by 20% and reduced tumour incidence. Besides, GB administration significantly improved healthspan evidenced by enhancement in muscle quality, physical performance, grip strength, metabolism, frailty index, systemic inflammation, and senescence. Moreover, GB administration ameliorated aging-related pathologies without any apparent adverse effects. Single-nucleus RNA sequencing (snRNA-seq) revealed that GB improved aging-associated abnormal cell-type composition, intracellular signalling pathways, and cell-cell communication in skeletal muscles. GB also reduced the levels of aging-induced novel Runx1+ type 2B myonuclei, which are associated with apoptotic burden and aging-related signatures. Runx1 derived senescence, as shown by gain- and loss-of-function assays. Together, a new function of GB in extending the healthspan in aging is identified, which contributes to lifespan extension. The senomorphic effects of GB on the multifactorial aging process may provide new prospects for achieving healthy aging and longevity extension.
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Project description:Geroscience aims to target the aging process to extend healthspan. However, even isogenic individuals show heterogeneity in natural aging rate and responsiveness to pro-longevity interventions, limiting translational potential. Using in vivo mini gene reporters in isogenic C. elegans, we show that alternative splicing of mRNAs related to lipid metabolism in young animals is coupled to subsequent life expectancy. Further, activity of RNA splicing factors REPO-1 and SFA-1 early in life modulates effectiveness of specific longevity interventions via POD-2/ACC1 and regulation of lipid utilization. In addition, early inhibition of REPO-1 renders animals refractory to late onset suppression of the TORC1 pathway. Together these data suggest that activity of RNA splicing factors and the metabolic landscape early in life can modulate responsiveness to longevity interventions and may explain variance in efficacy between individuals.
2025-11-07 | GSE292723 | GEO
Project description:Geroscience aims to target the aging process to extend healthspan. However, even isogenic individuals show heterogeneity in natural aging rate and responsiveness to pro-longevity interventions, limiting translational potential. Using in vivo mini gene reporters in isogenic C. elegans, we show that alternative splicing of mRNAs related to lipid metabolism in young animals is coupled to subsequent life expectancy. Further, activity of RNA splicing factors REPO-1 and SFA-1 early in life modulates effectiveness of specific longevity interventions via POD-2/ACC1 and regulation of lipid utilization. In addition, early inhibition of REPO-1 renders animals refractory to late onset suppression of the TORC1 pathway. Together these data suggest that activity of RNA splicing factors and the metabolic landscape early in life can modulate responsiveness to longevity interventions and may explain variance in efficacy between individuals.
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Project description:Identifying strategies to mitigate age-related physiological decline remains a central challenge. Transcriptional regulation is essential to organismal healthspan and a frequent therapeutic target in ageing research. The Integrator complex is a highly conserved regulator of transcriptional quality control and RNA processing, yet its role in ageing within an intact organism remains unknown. Using adult-specific RNAi in Caenorhabditis elegans, we find that depletion of most Integrator subunits extends lifespan and healthspan. Mechanistically, loss of the catalytic subunit INTS11 disrupts 3′ end formation of small nuclear and spliced-leader RNAs, impairing trans-splicing and promoting outron retention on a subset of transcripts enriched for spliceosomal, nucleocytoplasmic import and mitochondrial functions. These RNA-processing defects engage endogenous siRNA pathways, which are required for the longevity and healthspan benefits of INTS11 depletion, consistent with a role in buffering the cytoplasmic burden of misprocessed splicing and import factors. In parallel, outron retention compromises nuclear-encoded mitochondrial gene expression and induces a hormetic decline in mitochondrial function. Together, our findings identify Integrator as an upstream regulator of a coupled RNA-processing–small RNA–mitochondrial axis that shapes the pace of ageing.
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Project description:Identifying strategies to mitigate age-related physiological decline remains a central challenge. Transcriptional regulation is essential to organismal healthspan and a frequent therapeutic target in ageing research. The Integrator complex is a highly conserved regulator of transcriptional quality control and RNA processing, yet its role in ageing within an intact organism remains unknown. Using adult-specific RNAi in Caenorhabditis elegans, we find that depletion of most Integrator subunits extends lifespan and healthspan. Mechanistically, loss of the catalytic subunit INTS11 disrupts 3′ end formation of small nuclear and spliced-leader RNAs, impairing trans-splicing and promoting outron retention on a subset of transcripts enriched for spliceosomal, nucleocytoplasmic import and mitochondrial functions. These RNA-processing defects engage endogenous siRNA pathways, which are required for the longevity and healthspan benefits of INTS11 depletion, consistent with a role in buffering the cytoplasmic burden of misprocessed splicing and import factors. In parallel, outron retention compromises nuclear-encoded mitochondrial gene expression and induces a hormetic decline in mitochondrial function. Together, our findings identify Integrator as an upstream regulator of a coupled RNA-processing–small RNA–mitochondrial axis that shapes the pace of ageing.
2026-04-27 | GSE325597 | GEO
Project description:Identifying strategies to mitigate age-related physiological decline remains a central challenge. Transcriptional regulation is essential to organismal healthspan and a frequent therapeutic target in ageing research. The Integrator complex is a highly conserved regulator of transcriptional quality control and RNA processing, yet its role in ageing within an intact organism remains unknown. Using adult-specific RNAi in Caenorhabditis elegans, we find that depletion of most Integrator subunits extends lifespan and healthspan. Mechanistically, loss of the catalytic subunit INTS11 disrupts 3′ end formation of small nuclear and spliced-leader RNAs, impairing trans-splicing and promoting outron retention on a subset of transcripts enriched for spliceosomal, nucleocytoplasmic import and mitochondrial functions. These RNA-processing defects engage endogenous siRNA pathways, which are required for the longevity and healthspan benefits of INTS11 depletion, consistent with a role in buffering the cytoplasmic burden of misprocessed splicing and import factors. In parallel, outron retention compromises nuclear-encoded mitochondrial gene expression and induces a hormetic decline in mitochondrial function. Together, our findings identify Integrator as an upstream regulator of a coupled RNA-processing–small RNA–mitochondrial axis that shapes the pace of ageing.
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