ArticleNature2011
Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 232 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
232 citing papers in PubMed, 383 citations in OpenAlex.
- Direct Pharmacological Activation of AMPK Extends Lifespan in Yeast, Worms and Flies.Aging cell · 2026Article
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- Ribonuclease DIS3 delays aging and senescence by generating tRNA halves.Nature communications · 2026Article
- Pharmacologic AMPK Activation Extends Lifespan inbioRxiv : the preprint server for biology · 2026Article
- Fatty acid regulation of feeding inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- CREB suppresses PGRP-SC2 to drive age-related immune senescence and gut dysbiosis in Drosophila.Cell death discovery · 2026Article
- AKG-TET axis is central to senescence plasticity.iScience · 2026Article
- Article
- AMPK modulates a DEAH box RNA-helicase to attenuate TOR signaling and establish developmental quiescence in Caenorhabditis elegans.PLoS biology · 2025Article
- The protein phosphatase 6 subunit SAPS3 modulates lifespan by regulating metabolism.Science advances · 2025Article
- Lysosomes signal through the epigenome to regulate longevity across generations.Science (New York, N.Y.) · 2025Article
- Article
- Peripheral Blood Exosomal miR-184-3p in Methamphetamine Use Disorder: Biomarker Potential and CRTC1-Mediated Neuroadaptation.Current issues in molecular biology · 2025Article
- Article
- Chromatin and epigenetics in aging biology.Genetics · 2025Review
- Aging-Induced Episodic-Like Memory Impairment Could be Alleviated by Melatonin Treatment via Preserving Blood-Brain Barrier Integrity and Upregulating CRTC1.CNS neuroscience & therapeutics · 2025Article
- Longevity, enhanced memory, and altered density of dendritic spines in hippocampal CA3 and dentate gyrus after hemizygous deletion of Pde2a in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- The Impact of Rosemary and Ginger Extracts on Aging and Healthspan in Drosophila.Aging and disease · 2025Article
- Oral Transfer of Anti-Aging Substances: Key Chemical Found in Reproductive Caste of Termites.International journal of molecular sciences · 2025Article
- Serine metabolism in aging and age-related diseases.GeroScience · 2025Review
172 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Activating AMPK or inactivating calcineurin slows ageing in Caenorhabditis elegans and both have been implicated as therapeutic targets for age-related pathology in mammals. However, the direct targets that mediate their effects on longevity remain unclear. In mammals, CREB-regulated transcriptional coactivators (CRTCs) are a family of cofactors involved in diverse physiological processes including energy homeostasis, cancer and endoplasmic reticulum stress. Here we show that both AMPK and calcineurin modulate longevity exclusively through post-translational modification of CRTC-1, the sole C. elegans CRTC. We demonstrate that CRTC-1 is a direct AMPK target, and interacts with the CREB homologue-1 (CRH-1) transcription factor in vivo. The pro-longevity effects of activating AMPK or deactivating calcineurin decrease CRTC-1 and CRH-1 activity and induce transcriptional responses similar to those of CRH-1 null worms. Downregulation of crtc-1 increases lifespan in a crh-1-dependent manner and directly reducing crh-1 expression increases longevity, substantiating a role for CRTCs and CREB in ageing. Together, these findings indicate a novel role for CRTCs and CREB in determining lifespan downstream of AMPK and calcineurin, and illustrate the molecular mechanisms by which an evolutionarily conserved pathway responds to low energy to increase longevity.
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What OpenQuestion holds
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.