Cited by 186Genetics, Aging, and Longevity in Model OrganismsMetabolism, Diabetes, and CancerMitochondrial Function and Pathology

Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal

Open access
Burkewitz, Kristopher, Morantte, Ianessa, Weir, Heather J.M., Yeo, Robin, Zhang, Yue, Huynh, Frank K., Ilkayeva, Olga R., Hirschey, Matthew D. +2 more·2015·Cell

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.cell.2015.02.004

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Knockdown of CRTC-1 in C. elegans extends lifespan.

    “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

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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.
Venue
Cell
Publisher
Elsevier BV
Published
2015-02
Volume
160
Issue
5
Pages
842-855
ISSN
0092-8674 (ISSN-L)
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review