ArticleThe Journal of biological chemistry2016
Reciprocal Changes in Phosphoenolpyruvate Carboxykinase and Pyruvate Kinase with Age Are a Determinant of Aging in Caenorhabditis elegans.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Age-dependent physiological responses and longevity in three Drosophila species with contrasting lifespans exposed to low temperature and constant darkness.Biogerontology · 2026Article
- Persistent effects of early-life arsenic exposure inEnvironmental science. Processes & impacts · 2026Article
- Pyruvate kinase deficiency links metabolic perturbations to neurodegeneration and axonal protection.Molecular metabolism · 2025Article
- Article
- Molecular Mechanisms for Anti-aging of Low-Vacuum Cold Plasma Pretreatment in Caenorhabditis elegans.Applied biochemistry and biotechnology · 2022Article
- Evaluation of lifespan promoting effects of biofortified wheat in Drosophila melanogaster.Experimental gerontology · 2022Article
- Untargeted muscle tissue metabolites profiling in young, adult, and old rats supplemented with tocotrienol-rich fraction.Frontiers in molecular biosciences · 2022Article
- The Q system for conditional gene expression is leaky and lacks dynamic range inmicroPublication biology · 2022Article
- Restoration of energy homeostasis by SIRT6 extends healthy lifespan.Nature communications · 2021Article
- Targeting metabolic pathways for extension of lifespan and healthspan across multiple species.Ageing research reviews · 2020Review
- Article
- Gluconeogenesis and PEPCK are critical components of healthy aging and dietary restriction life extension.PLoS genetics · 2020Article
- Succinate Dehydrogenase-Regulated Phosphoenolpyruvate Carboxykinase Sustains Copulation Fitness in Aging C. elegans Males.iScience · 2020Article
- Article
- Gluconeogenesis in cancer cells - Repurposing of a starvation-induced metabolic pathway?Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Dynamic Acetylation of Phosphoenolpyruvate Carboxykinase Toggles Enzyme Activity between Gluconeogenic and Anaplerotic Reactions.Molecular cell · 2018Article
- Aging: T cell metabolism within tumors.Aging · 2016Article
- Reprogramming of energy metabolism as a driver of aging.Oncotarget · 2016Review
- Erythropoietin ameliorates hyperglycemia in type 1-like diabetic rats.Drug design, development and therapy · 2016Article
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
Aging involves progressive loss of cellular function and integrity, presumably caused by accumulated stochastic damage to cells. Alterations in energy metabolism contribute to aging, but how energy metabolism changes with age, how these changes affect aging, and whether they can be modified to modulate aging remain unclear. In locomotory muscle of post-fertile Caenorhabditis elegans, we identified a progressive decrease in cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), a longevity-associated metabolic enzyme, and a reciprocal increase in glycolytic pyruvate kinase (PK) that were necessary and sufficient to limit lifespan. Decline in PEPCK-C with age also led to loss of cellular function and integrity including muscle activity, and cellular senescence. Genetic and pharmacologic interventions of PEPCK-C, muscle activity, and AMPK signaling demonstrate that declines in PEPCK-C and muscle function with age interacted to limit reproductive life and lifespan via disrupted energy homeostasis. Quantifications of metabolic flux show that reciprocal changes in PEPCK-C and PK with age shunted energy metabolism toward glycolysis, reducing mitochondrial bioenergetics. Last, calorie restriction countered changes in PEPCK-C and PK with age to elicit anti-aging effects via TOR inhibition. Thus, a programmed metabolic event involving PEPCK-C and PK is a determinant of aging that can be modified to modulate aging.
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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.