ArticleAging cell2016
Mitochondrial metabolites extend lifespan.
Article in Aging cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 54 citations in OpenAlex.
- Transcriptome analyses describe the consequences of persistent HIF-1 over-activation in Caenorhabditis elegans.PloS one · 2024Article
- Modifications of Blood Molecular Components after Treatment with Low Ozone Concentrations.International journal of molecular sciences · 2023Article
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- Amyotrophic lateral sclerosis alters the metabolic aging profile in patient derived fibroblasts.Neurobiology of aging · 2021Article
- Tolerance to NADH/NADiScience · 2021Article
- Targeting metabolic pathways for extension of lifespan and healthspan across multiple species.Ageing research reviews · 2020Review
- Composition of Caenorhabditis elegans extracellular vesicles suggests roles in metabolism, immunity, and aging.GeroScience · 2020Article
- Genetic and metabolomic architecture of variation in diet restriction-mediated lifespan extension in Drosophila.PLoS genetics · 2020Article
- Review
- Automated lifespan determination across Caenorhabditis strains and species reveals assay-specific effects of chemical interventions.GeroScience · 2019Article
- Lactate and pyruvate promote oxidative stress resistance through hormetic ROS signaling.Cell death & disease · 2019Article
- Article
- Mechanisms Through Which Some Mitochondria-Generated Metabolites Act as Second Messengers That Are Essential Contributors to the Aging Process in Eukaryotes Across Phyla.Frontiers in physiology · 2019Review
- Emerging topics in C. elegans aging research: Transcriptional regulation, stress response and epigenetics.Mechanisms of ageing and development · 2019Review
- BRCA1 and BARD1 mediate apoptotic resistance but not longevity upon mitochondrial stress inEMBO reports · 2018Article
- Small-Scale Colorimetric Assays of Intracellular Lactate and Pyruvate in the Nematode Caenorhabditis elegans.Journal of visualized experiments : JoVE · 2018Article
- Genetic inhibition of an ATP synthase subunit extends lifespan in C. elegans.Scientific reports · 2018Article
- Axonal Mitochondria Modulate Neuropeptide Secretion Through the Hypoxic Stress Response inGenetics · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Disruption of mitochondrial respiration in the nematode Caenorhabditis elegans can extend lifespan. We previously showed that long-lived respiratory mutants generate elevated amounts of α-ketoacids. These compounds are structurally related to α-ketoglutarate, suggesting they may be biologically relevant. Here, we show that provision of several such metabolites to wild-type worms is sufficient to extend their life. At least one mode of action is through stabilization of hypoxia-inducible factor-1 (HIF-1). We also find that an α-ketoglutarate mimetic, 2,4-pyridinedicarboxylic acid (2,4-PDA), is alone sufficient to increase the lifespan of wild-type worms and this effect is blocked by removal of HIF-1. HIF-1 is constitutively active in isp-1(qm150) Mit mutants, and accordingly, 2,4-PDA does not further increase their lifespan. Incubation of mouse 3T3-L1 fibroblasts with life-prolonging α-ketoacids also results in HIF-1α stabilization. We propose that metabolites that build up following mitochondrial respiratory dysfunction form a novel mode of cell signaling that acts to regulate lifespan.
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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.