The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Neuronal CRTC-1 Governs Systemic Mitochondrial Metabolism and Lifespan via a Catecholamine Signal
Open accessAbstract
Low energy states delay aging in multiple species, yet mechanisms coordinating energetics and longevity across tissues remain poorly defined. The conserved energy sensor AMP-activated protein kinase (AMPK) and its corresponding phosphatase calcineurin modulate longevity via the CREB regulated transcriptional coactivator (CRTC)-1 in C. elegans. We show that CRTC-1 specifically uncouples AMPK/calcineurin-mediated effects on lifespan from pleiotropic side effects by reprogramming mitochondrial and metabolic function. This pro-longevity metabolic state is regulated cell nonautonomously by CRTC-1 in the nervous system. Neuronal CRTC-1/CREB regulates peripheral metabolism antagonistically with the functional PPARα ortholog, NHR-49, drives mitochondrial fragmentation in distal tissues, and suppresses the effects of AMPK on systemic mitochondrial metabolism and longevity via a cell-nonautonomous catecholamine signal. These results demonstrate that while both local and distal mechanisms combine to modulate aging, distal regulation overrides local contribution. Targeting central perception of energetic state is therefore a potential strategy to promote healthy aging.
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“knockdown of CRTC-1 in C. elegans extends lifespan (Burkewitz et al., 2015).”
From The Aging Epigenome (2016) · cites this paper as Burkewitz et al., 2015
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Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668
REVIGO summarizes and visualizes long lists of gene ontology terms
Supek, F., Bošnjak, M., Škunca, N., & Šmuc, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021800 · Cited by 6,264
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602
Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., et al. (2011) · Science · doi:10.1126/science.1196371 · Cited by 2,600
Self-citationAMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus
Minokoshi, Y., Alquier, T., Furukawa, N., Kim, Y.-B., Lee, A., Xue, B., Mu, J., Foufelle, F., Ferré, P., Birnbaum, M. J., et al. (2004) · Nature · doi:10.1038/nature02440 · Cited by 1,637
Metformin improves healthspan and lifespan in mice
Martin-Montalvo, A., Mercken, E. M., Mitchell, S. J., Palacios, H. H., Mote, P. L., Scheibye-Knudsen, M., Gomes, A. P., Ward, T. M., Minor, R. K., Blouin, M.-J., et al. (2013) · Nature Communications · doi:10.1038/ncomms3192 · Cited by 1,445
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Bao, H., Cao, J., Chen, M., Min, C., Chen, W., Chen, X., Chen, Y., Chen, Y., Chen, Y., Chen, Z., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2305-0 · Cited by 402
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Self-citationLiu, Y. J., McIntyre, R. L., Janssens, G. E., & Houtkooper, R. H. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111212 · Cited by 347
Metadata
- Authors
- Burkewitz, K., Morantte, I., Weir, H. J. M., Yeo, R., Zhang, Y., Huynh, F. K., Ilkayeva, O. R., Hirschey, M. D., Grant, A. R., & Mair, W. B.
- Affiliations
- Harvard University (US)
- Duke University (US)
- University of Michigan (US)
- Corresponding author
- Mair, William B.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 160
- Issue
- 5
- Pages
- 842-855
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4392909
- OpenAlex
- W2064550415
- Cited by
- 186
- References
- 47
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 14 · 2023: 14 · 2022: 24 · 2021: 19 · 2020: 23 · 2019: 17 · 2018: 15 · 2017: 21 · 2016: 20 · 2015: 6
- FWCI
- 8.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Diabetes Association
- Ellison Medical Foundation
- National Institutes of Health
- National Institute on Aging (R01AG045351, R01AG044346, F32AG044944)
- National Cancer Institute (U54CA155626)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- lifespan, aging, mitochondrial metabolism, AMPK, calcineurin, CREB, catecholamine signaling, neuronal regulation, PPARα, NHR-49, mitochondrial fragmentation, Caenorhabditis elegans, energy sensing
- MeSH terms
- Animals, Catecholamines, Longevity, Mitochondria, Neurons, Signal Transduction, Trans-Activators, Caenorhabditis elegans, Cyclic AMP Response Element-Binding Protein, Receptors, Cytoplasmic and Nuclear, Caenorhabditis elegans Proteins, AMP-Activated Protein Kinases
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