ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
20S proteasome activation promotes life span extension and resistance to proteotoxicity in Caenorhabditis elegans.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed.
- Coordinated control of proteasome subunit gene expression promotes stress resistance, proteostasis, and longevity.GeroScience · 2026Article
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- FOXO family and neurodegenerative diseases: Mechanisms of action and therapeutic potential.Redox biology · 2026Review
- Composition and activity of the proteasome in human iPSC-derived neuronal model of early-stage sporadic Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Translational Insights into Exercise-Induced Protective Adaptations in 5XFAD Mice and Middle-Aged Amateur Sportsmen.Antioxidants (Basel, Switzerland) · 2026Article
- Hyperactive 20Science advances · 2025Article
- Recent Advancements in 20S Proteasome Enhancement: Degradation of Undruggable Targets.ACS medicinal chemistry letters · 2025Review
- Changing landscape of hematopoietic and mesenchymal cells and their interactions during aging and in age-related skeletal pathologies.Mechanisms of ageing and development · 2025Review
- Unraveling Molecular Targets for Neurodegenerative Diseases ThroughInternational journal of molecular sciences · 2025Review
- Article
- The DYT6 dystonia causative protein THAP1 is responsible for proteasome activity via PSMB5 transcriptional regulation.Nature communications · 2025Article
- β-Amyloid impairs Proteasome structure and function. Proteasome activation mitigates amyloid induced toxicity and cognitive deficits.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms and regulation of substrate degradation by the 26S proteasome.Nature reviews. Molecular cell biology · 2025Review
- Altered Proteasome Composition in Aging Brains, Genetic Proteasome Augmentation Mitigates Age-Related Cognitive Declines, and Acute Proteasome Agonist Treatment Rescues Age-Related Cognitive Deficits in Mice.bioRxiv : the preprint server for biology · 2024Article
- Primed for Interactions: Investigating the Primed Substrate Channel of the Proteasome for Improved Molecular Engagement.Molecules (Basel, Switzerland) · 2024Review
- Floxuridine supports UPS independent of germline signaling and proteostasis regulators via involvement of detoxification in C. elegans.PLoS genetics · 2024Article
- Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement.ACS chemical neuroscience · 2024Review
- Proteasome Activators and Ageing: Restoring Proteostasis Using Small Molecules.Sub-cellular biochemistry · 2024Review
- The proteasome as a drug target for treatment of parasitic diseases.Advances in parasitology · 2024Review
- A novel endoplasmic reticulum adaptation is critical for the long-lived Caenorhabditis elegans rpn-10 proteasomal mutant.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein homeostasis (proteostasis) is one of the nodal points that need to be preserved to retain physiologic cellular/organismal balance. The ubiquitin-proteasome system (UPS) is responsible for the removal of both normal and damaged proteins, with the proteasome being the downstream effector. The proteasome is the major cellular protease with progressive impairment of function during aging and senescence. Despite the documented age-retarding properties of proteasome activation in various cellular models, simultaneous enhancement of the 20S core proteasome content, assembly, and function have never been reported in any multicellular organism. Consequently, the possible effects of the core proteasome modulation on organismal life span are elusive. In this study, we have achieved activation of the 20S proteasome at organismal level. We demonstrate enhancement of proteasome levels, assembly, and activity in the nematode Caenorhabditis elegans, resulting in life span extension and increased resistance to stress. We also provide evidence that the observed life span extension is dependent on the transcriptional activity of Dauer formation abnormal/Forkhead box class O (DAF-16/FOXO), skinhead-1 (SKN-1), and heat shock factor-1 (HSF-1) factors through regulation of downstream longevity genes. We further show that the reported beneficial effects are not ubiquitous but they are dependent on the genetic context. Finally, we provide evidence that proteasome core activation might be a potential strategy to minimize protein homeostasis deficiencies underlying aggregation-related diseases, such as Alzheimer's disease (AD) or Huntington's disease (HD). In summary, this is the first report demonstrating that 20S core proteasome up-regulation in terms of both content and activity is feasible in a multicellular eukaryotic organism and that in turn this modulation promotes extension of organismal health span and life span.
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