ArticleProceedings of the National Academy of Sciences of the United States of America2014
Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
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Who cites it
133 citing papers in PubMed, 192 citations in OpenAlex.
- Intervening on Calorie Intake or Eating Timing in Older Adults: Lessons Learned in the Healthy Aging and Late-Life Outcomes Randomized Controlled Pilot Trial.Clinical interventions in aging · 2025Trial
- Elevated mitochondrial superoxide promotes longevity through a mitochondria-to-nucleus kinase signaling pathway.Redox biology · 2026Article
- The Extended Lifespan ofCurrent issues in molecular biology · 2026Article
- Article
- Multiple Molecular Pathways to Longevity: Opposing Gene Expression Programs Define Distinct Aging Strategies.bioRxiv : the preprint server for biology · 2026Article
- MAK-2 Kinase Is Required for Extended Longevity and Enhanced Stress Resistance Resulting From Mild Impairment of Mitochondrial Function in isp-1 Mutants.Aging cell · 2026Article
- Review
- Mild Mitochondrial Impairment Activates Overlapping Longevity Pathways Converging on the Flavin-Containing Monooxygenase FMO-2.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial superoxide regulates nuclear envelope integrity and ageing via redox-mediated lipid metabolism.Nature metabolism · 2026Article
- Multilayered regulation of longevity in Caenorhabditis elegans.Molecules and cells · 2026Review
- Article
- Mild mitochondrial impairment activates overlapping longevity pathways converging on the flavin-containing monooxygenase FMO-2.Frontiers in aging · 2026Article
- HIF-1α-mediated feedback prevents TOR signalling from depleting oxygen supply and triggering stress during normal development.Nature communications · 2025Article
- Iron-deplete diet enhances Caenorhabditis elegans lifespan via oxidative stress response pathways.The EMBO journal · 2025Article
- Iron-deplete diet enhancesbioRxiv : the preprint server for biology · 2025Article
- Ferritinophagy Loss Drives Mitochondrial Iron Import and Colorectal Tumorigenesis.Research square · 2025Article
- Stress responses and dynamic equilibrium: Key determinants of aging in thebioRxiv : the preprint server for biology · 2025Article
- Forward genetics ineLife · 2025Article
- Exploring the regulatory roles of AtGLR3.4 receptors in mitochondrial stress and ROS management in Arabidopsis.Plant cell reports · 2025Article
- Dysfunctional tetraspanin 7 (TSP-7) in Caenorhabditis elegans promotes; increases in average life- & health-span, stress-induced survival and motility.FEBS open bio · 2025Article
73 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Mild inhibition of mitochondrial respiration extends the lifespan of many species. In Caenorhabditis elegans, reactive oxygen species (ROS) promote longevity by activating hypoxia-inducible factor 1 (HIF-1) in response to reduced mitochondrial respiration. However, the physiological role and mechanism of ROS-induced longevity are poorly understood. Here, we show that a modest increase in ROS increases the immunity and lifespan of C. elegans through feedback regulation by HIF-1 and AMP-activated protein kinase (AMPK). We found that activation of AMPK as well as HIF-1 mediates the longevity response to ROS. We further showed that AMPK reduces internal levels of ROS, whereas HIF-1 amplifies the levels of internal ROS under conditions that increase ROS. Moreover, mitochondrial ROS increase resistance to various pathogenic bacteria, suggesting a possible association between immunity and long lifespan. Thus, AMPK and HIF-1 may control immunity and longevity tightly by acting as feedback regulators of ROS.
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Registered trials
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.