Caenorhabditis elegans
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA337916 | ENA |
REPOSITORIES: ENA
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Project description:Aging is a major international concern and brings with it formidable socioeconomical and healthcare challenges. An attainable approach to improve general health in humans is using small molecules. Tomatidine, a natural compound abundant in unripe tomatoes, inhibits aging-related skeletal muscle atrophy in mice. Here we show that tomatidine extends lifespan and healthspan in the aging animal model C. elegans, which shares many major longevity pathways with those of mammals. Tomatidine improves behaviors related to healthspan, including increased pharyngeal pumping and swimming movement, and also reduces deterioration of muscle cells in worms. Microarray, imaging, and behavioral analysis reveal that tomatidine maintains mitochondrial homeostasis through mitochondrial biogenesis and PINK-1/DCT-1-dependent mitophagy. Mechanistically, tomatidine induces mitochondrial hormesis by mildly inducing ROS production, which in turn activates the cellular antioxidant response SKN-1/Nrf2 pathway, followed by increased mitophagy in worms, primary rat neurons, and human cells. Our data suggest that tomatidine may delay some physiological aspects of aging, and points to new approaches for pharmacological interventions towards diseases of aging.
2017-08-21 | GSE85237 | GEO
Project description:Mitochondrial damage and mitophagy deregulation are hallmark features of aging and age-related pathologies. Urolithin A (UA), a potent mitophagy inducer, is known to confer neuroprotection, maintain muscle integrity, and extend healthspan and lifespan across diverse species. However, the molecular mechanisms underlying UA-mediated mitophagy remain largely unknown. Here, we demonstrate that UA treatment modulates cytosolic calcium levels, which are essential for initiating robust mitophagy in both neurons and muscles. Transcriptomic and proteomic analyses reveal that UA facilitates the reorganization of interorganellar communication between the endoplasmic reticulum (ER), lysosomes, and mitochondria, a process that is highly dependent on calcium signaling. Our findings suggest that calcium is released from the ER, subsequently enhancing lysosomal activity and facilitating mitochondrial entry, ultimately leading to mitochondrial fission and the successful execution of mitophagy. Notably, calcium chelation abolishes UA-induced mitophagy, leading to impaired muscle function and diminished lifespan extension, underscoring the indispensable role of calcium dynamics.We further found that UA-induced calcium elevation triggers mitochondrial biogenesis through the activation of UNC-43/CaMKII and SKN-1/Nrf2, mechanisms critical for healthspan and lifespan extension. In human cells, UA supplementation not only induces mitophagy but also enhances mitochondrial metabolism and prevents stress-induced senescence in a calcium-dependent manner. Ultimately, our findings uncover the mechanistic insights of UA-mediated geroprotection and underscore the central role of calcium dynamics in orchestrating the crosstalk between different cellular compartments, thereby sustaining energy homeostasis and overall organismal physiology.
2025-10-15 | PXD056571 | Pride
Project description:Mitochondrial dysfunction and mitophagy deregulation are hallmark features of aging and age-related pathologies. Urolithin A (UA), a potent mitophagy inducer, is known to confer neuroprotection, maintain muscle integrity, and extend healthspan and lifespan across diverse species. Nonetheless, the molecular mechanisms underlying UA-mediated mitophagy remain largely unknown. Here, we demonstrate that UA treatment modulates cytosolic calcium levels, which are essential for initiating robust mitophagy in both neurons and muscles. Transcriptomic and proteomic analyses reveal that UA facilitates the reorganization of inter-organellar communication between endoplasmic reticulum (ER), lysosomes and mitochondria; processes that are highly dependent on calcium signaling. Our findings suggest that UA induces calcium release from the ER and enhances lysosomal activity, while downstream uptake of released calcium from mitochondria, ultimately leads to mitochondrial fission and the successful execution of mitophagy. Consistently, calcium chelation abolishes UA-induced mitophagy, leading to impaired muscle function and diminishes lifespan extension, underscoring the critical role of calcium dynamics. We further found that UA-induced calcium elevation triggers mitochondrial biogenesis through the activation of UNC-43/CaMKII and SKN-1/Nrf2; these pathways are also critical for healthspan and lifespan extension. In human cells, UA supplementation not only induces mitophagy but also enhances mitochondrial metabolism and prevents stress-induced senescence in a calcium-dependent manner. Ultimately, our findings uncover the mechanistic insights of UA-mediated geroprotection and underscore the central role of calcium dynamics in orchestrating the crosstalk and functional wiring of different cellular compartments, thereby sustaining energy homeostasis and overall organismal physiology.
2026-01-12 | GSE279559 | GEO
Project description:The role of ellagic acid (EA), a natural antioxidant, in regulating anti-aging and its underlying mechanisms remains unclear. In this study, we investigated the anti-aging effects and molecular mechanisms of EA in Caenorhabditis elegans (C. elegans). Our results demonstrate that EA extends the lifespan of C. elegans, enhances motility, reduces lipofuscin accumulation, and improves overall healthspan. Additionally, EA reduces reactive oxygen species (ROS) accumulation in C. elegans under conditions of heat and oxidative stress. The insulin/IGF-1 signaling (IIS) pathway, a key regulator of longevity and stress resistance in C. elegans, was found to mediate EA's effects. EA treatment did not extend the lifespan of mutants defective in daf-2, daf-16, hsf-1, hlh-30, and skn-1, confirming that EA’s lifespan-extending effect operates through the IIS pathway. Furthermore, EA treatment increased the expression of stress response genes downstream of the IIS pathway. Based on RNA sequencing data, we further explored the molecular mechanisms and potential regulatory roles of EA in anti-aging.
2025-05-10 | GSE295741 | GEO
Project description:Pimozide is a potent inhibitor of dopamine-like D2-like receptors (D2R) and has been approved by the FDA and widely used in clinical treatment. Although various monoamine antipsychotic drugs have shown potential as anti-aging agents, the role of pimozide in aging remains unclear. We found that pimozide can extend the lifespan of C. elegans, as well as its healthy lifespan, manifested by increased activity, reduced accumulation of lipofuscin, and enhanced stress resistance. RNA-seq results showed that pimozide significantly upregulated the expression of collagen genes and induced an increase in collagen protein synthesis. Moreover, pimozide extends the lifespan of nematodes through the skn-1 pathway, while in skn-1(EU-1), the lifespan-extending effect of pimozide is eliminated. In summary, these findings indicate that pimozide can promote the health and lifespan of C. elegans through the skn-1-collagen pathway.
2026-08-19 | GSE338120 | GEO
Project description:Reactive Oxygen Species increase gradually with aging and Steadily diminish the cell's ability to maintain homeostasis. Nuclear Factor-like 2 and its C elegans ortholog, SKN-1 are transcription factors that play a pivotal role in oxidative stress response, cellular homeostasis and lifespan. But like other defence systems, Nrf2-mediated stress response is compromised in aging and neurodegenerative diseases. In this study we provide evidence that this FDA-approved drug is a bona fide activator of Nrf2/SKN-1 pathway.
2016-12-21 | MSV000080435 | MassIVE
Project description:D-Glucosamine (2-amino-2-deoxy-D-glucose, C.A.S.# 3416-24-8) (GlcN) is a freely available and commonly used dietary supplement possibly promoting cartilage health in humans which also acts as an inhibitor of glycolysis. We here find that GlcN extends C. elegans lifespan by impairing glucose metabolism to activate AMP-activated protein kinase (AMPK/AAK2) leading to increased mitochondrial biogenesis. Consistent with the concept of mitohormesis, this promotes increased formation of mitochondrial reactive oxygen species (ROS) and p38/PMK-1-mediated stress signaling culminating in increased expression of the nematodal amino acid-transporter 1 (aat-1) gene. Ameliorating mitochondrial ROS formation as well as impairment of aat-1-expression abolishes GlcN-mediated lifespan extension in a NRF2/SKN-1-dependent fashion. Notably and unlike other calorie restriction mimetics (CRM) like 2-deoxy-D-glucose (2DG, DOG), GlcN extends lifespan of aging C57BL/6 mice (log-rank: p=0.002; cox regression: p=0.01) similarly paralleled by an induction of mitochondrial biogenesis, increased expression of several murine amino acid transporters, as well as increased amino-acid catabolism. Taken together, GlcN mimics a ketogenic diet to extend healthspan in evolutionary distinct species. 24 samples: 12 mRNA profiles of C.elegans: 6 without GlcN and 6 with GlcN supplementaion; 12 mRNA profiles of M.musculus: 6 without GlcN and 6 with GlcN supplementaion
2014-03-07 | E-GEOD-54853 | biostudies-arrayexpress
Project description:Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that generates free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. Mammalian NF-E2-related factor 2 (Nrf2) and its C. elegans ortholog SKN-1, mediate protective responses to oxidative stress by promoting target gene expression via antioxidant response elements (ARE). Genetic analyses showed that skn-1 mediates plumbagin’s lifespan-extending effect in C. elegans. Further screening of a series of plumbagin analogs identified three additional naphthoquinones that could induce SKN-1 targets in C. elegans. Naphthazarin showed skn-1-dependent lifespan extension, over an extended dose range compared to plumbagin, while the other naphthoquinones, oxoline and menadione, had differing effects on C. elegans survival and failed to activate ARE reporter expression in cultured mammalian cells. Our findings reveal the potential for low doses of naturally occurring naphthoquinones to extend lifespan by engaging a specific adaptive cellular stress response pathway.
2012-03-21 | GSE28301 | GEO
Project description:Mitis group streptococci are opportunistic pathogens residing in the oral cavity, where they produce hydrogen peroxide (H2O2), a key virulence factor contributing to their pathogenesis. We previously demonstrated that these bacteria kill the nematode Caenorhabditis elegans through H2O2 production. Metformin, a widely used biguanide drug for managing blood glucose levels, has shown promising effects on aging by extending lifespan in worms and mice, and has also demonstrated potential cancer treatment. Additionally, pretreatment with metformin enhances the survival of worms and triggers an immune response via the p38 MAPK pathway against various pathogenic bacteria. Based on these observations, we investigated metformin's potential as a therapeutic agent against mitis group streptococcal infections and its underlying mechanisms in the current study. Pretreatment of worms with metformin provided significant dose-dependent protection from streptococcal-derived H2O2. This protective effect was attributed to the activation of the oxidative stress response transcription factor SKN-1/NRF2. Further analysis revealed that the p38 MAPK pathway and the transcription mediator complex protein MDT-15 are essential for the activation of SKN-1 by metformin. Interestingly, SKN-1 activity, mediated by MDT-15, was found to be independent of the p38 MAPK pathway. Our findings establish that metformin-mediated protection against mitis group streptococcal infections relies on the coordinated action of SKN-1, the p38 MAPK pathway, and MDT-15. These insights suggest that metformin could be a valuable therapeutic agent in combating these infections. Future research should focus on further elucidating the molecular mechanisms involved and exploring the potential clinical applications of metformin in treating these bacterial infections.
2026-08-07 | PXD071991 | Pride
Project description:The C. elegans lifespan in the presence of Bacillus licheniformis caused induction of a large number of genes associated with anti-aging activiy including beta-oxidation Inaddition, these results indicate the B. licheniformis enhances the lifespan of Caenorhabditis elegans through serotonin signaling
2015-11-05 | GSE63056 | GEO