ArticleMolecular metabolism2013
Neuronal ROS signaling rather than AMPK/sirtuin-mediated energy sensing links dietary restriction to lifespan extension.
Article in Molecular metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 151 citations in OpenAlex.
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- Cycloastragenol Improves Fatty Acid Metabolism Through NHR-49/FAT-7 Suppression and Potent AAK-2 Activation inInternational journal of molecular sciences · 2026Article
- Multilayered regulation of longevity in Caenorhabditis elegans.Molecules and cells · 2026Review
- The heat shock factor Cbr-HSF-1 is necessary for lifespan maintenance inmicroPublication biology · 2026Article
- From Worms to Tumors: Conserved Strategies of Cellular Arrest and Survival Governing Dormancy.Cancer research · 2025Review
- Genome-Wide Temporal Gene Expression Reveals a Post-Reproductive Shift in the Nematode Caenorhabditis briggsae.Genome biology and evolution · 2025Article
- DEAD-box RNA helicase DDX-23 mediates dietary restriction induced health span in Caenorhabditis elegans.GeroScience · 2025Article
- Fmo induction as a tool to screen for pro-longevity drugs.GeroScience · 2024Article
- Multi-Omics Integrative Analysis to Reveal the Impacts ofInternational journal of molecular sciences · 2024Article
- Mitophagy-promoting agents and their ability to promote healthy-aging.Biochemical Society transactions · 2023Article
- All-optical spatiotemporal mapping of ROS dynamics across mitochondrial microdomains in situ.Nature communications · 2023Article
- Changes in the Mitochondria in the Aging Process-Can α-Tocopherol Affect Them?International journal of molecular sciences · 2023Review
- Astaxanthin promotes mitochondrial biogenesis and antioxidant capacity in chronic high-intensity interval training.European journal of nutrition · 2023Article
- Dioscin integrates regulation of monosaturated fatty acid metabolism to extend the life span through XBP-1/SBP-1 dependent manner.iScience · 2023Article
- Usnic Acid extends healthspan and improves the neurodegeneration diseases via mTOR/PHA-4 signaling pathway iniScience · 2022Article
- Mitochondrial succinate dehydrogenase function is essential for sperm motility and male fertility.iScience · 2022Article
- Stimulation of RAS-dependent ROS signaling extends longevity by modulating a developmental program of global gene expression.Science advances · 2022Article
- Mitochondrial dysfunction, aging, and the mitochondrial unfolded protein response in Caenorhabditis elegans.Genetics · 2022Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dietary restriction (DR) extends lifespan and promotes metabolic health in evolutionary distinct species. DR is widely believed to promote longevity by causing an energy deficit leading to increased mitochondrial respiration. 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. However, complex I inhibition does not further extend lifespan in dietarily restricted nematodes, indicating that impaired complex I activity mimics DR. Promotion of longevity due to complex I inhibition occurs independently of known energy sensors, including DAF-16/FoxO, as well as AAK-2/AMPK and SIR-2.1/sirtuins, or both. Consistent with the concept of mitohormesis, complex I inhibition transiently increases mitochondrial formation of reactive oxygen species (ROS) that activate PMK-1/p38 MAP kinase and SKN-1/NRF-2. Interference with this retrograde redox signal as well as ablation of two redox-sensitive neurons in the head of the worm similarly prevents extension of lifespan. These findings unexpectedly indicate that DR extends organismal lifespan through transient neuronal ROS signaling rather than sensing of energy depletion, providing unexpected pharmacological options to promote exercise capacity and healthspan despite unaltered eating habits.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.