Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal
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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. Strikingly, this pro-longevity metabolic state is regulated cell-nonautonomously by CRTC-1 in the nervous system. CRTC-1/CREB act antagonistically with the functional PPARα ortholog, NHR-49 to promote distinct peripheral metabolic programs. Neuronal CRTC-1 drives mitochondrial f
ORGANISM(S): Caenorhabditis elegans
SUBMITTER: Ana Grant
PROVIDER: E-GEOD-58931 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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