Figure 7. Neuronal CRTC-1 Regulates Longevity and Mitochondrial Function Cell Nonautonomously through Catecholamine Signaling(A) Normalized read counts for enzymes involved in synthesis of biogenic amines from the RNA-Seq analysis (see also Table S2).(B) qRT-PCR validating AMPK/CRTC-1 regulation of
tbh-1 transcript levels (Mean ± SEM of mRNA levels extracted from 2-4 samples of 50-100 animals; * denotes p < 0.05 by t test).(C) The biosynthetic pathway of octopamine.(D) Fluorescence imaging of a worm co-expressing CRTC-1::tdTOMATO from the native
crtc-1 promoter (top left) and GFP driven by the
tbh-1 promoter reveals CRTC-1 expression in octopaminergic RIC neurons.(E and F) Fluorescence imaging (top) and binary representations (bottom) of the mitochondrial network in muscle cells of animals vehicle-treated (water) or grown on media with 5 mM octopamine (F).(G) Classifying worms by their mitochondrial morphology reveals a 45% decline in the fraction of worms with tubular mitochondria treated with octopamine versuscontrol (p < 0.001 by t test; mean ± SD of n = 3 samples of 11-19 worms).(H-M) Survival curves demonstrating that neuron-specific activation of CRTC-1S76A,S179A suppresses both AMPK- (H) and calcineurin-mediated (K) lifespan extension. However, neuronal CRTC-1S76A,S179A has no effect on AMPK or calcineurin-mediated longevity in animals lacking functional
tdc-1 (I, L) or
tbh-1 (J, M).Genetic backgrounds are noted next to the origin. See Table S1 for lifespan statistics.