Enhanced survival benefits in SMA worm models are mediated by the daf-2/daf-16 pathway. A, Knock-down daf-16 by RNAi feeding shortens lifespan of smn-1(ok355) mutant animals by 12.5% when compared to EV (p < 0.001, Log-rank test). B, smn-1(ok355);daf-2(e1370) mutant animals live three more days than smn-1(ok355) mutant animals, and this beneficial effect is suppressed by feeding RNAi targeting daf-16 (p < 0.001, Log-rank test). C, smn-1(rt248);daf-2(e1370) mutant animals live 15 d, and this beneficial effect is suppressed by feeding RNAi that targets all isoforms of daf-16 (p < 0.001, Log-rank test). Feeding RNAi that targets daf16a or daf16f isoforms also suppress the longevity of smn-1(rt248);daf-2(e1370) mutant animals although the effect is less robust than the pan daf-16 RNAi effect (p < 0.001, Log-rank test). D, Overexpression of daf-16 using TJ356 (daf-16::gfp) strain prolongs lifespan of smn-1(ok355) mutant animals by 43.8% when compared to smn-1(ok355) mutant animals (p < 0.001, Log-rank test).