a, RNAi for crtc-1 or tax-6 has no effect in a tax-6 (ok2065) mutant background (log rank, P = 0.28 and P = 0.73, respectively). b, Mutations to the conserved AMPK target sites serines 76 and 179 together are sufficient to retain CRTC-1::RFP in the nucleus (×10). Insets are magnification of intestinal region. c, CRTC-1(S76A,S179A) is refractory to both tax-6 RNAi and AAK-2 overexpressor (o/e) in C. elegans intestinal cells (×40). White dashed lines and arrows indicate nuclei. d, RNAi of tax-6 extends the lifespan of C. elegans expressing wild-type CRTC-1::RFP (log rank, P < 0.0001), but has no effect on the S76A, S179A double mutant (log rank, P = 0.57). There is no significant difference between the lifespans of CRTC-1::RFP and CRTC-1(S76A,S179A) fed empty vector (log rank, P = 0.48). d, AAK-2 (aa 1–321) overexpression increases wild-type lifespan (log rank, P < 0.0001) but has no effect on worms expressing CRTC-1 (S6A, S179A) (log rank, P = 0.65).