Inactivation of daf-2/IGF-1 like signaling pathway extend lifespan in SMA worm models. Inactivation of daf-2/IGF-1 like signaling pathway extend lifespan.

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Inactivation of daf-2/IGF-1 like signaling pathway extend lifespan in SMA worm models. Inactivation of daf-2/IGF-1 like signaling pathway extend lifespan in SMA worm models. A, Lifespan analysis of N2, smn-1(ok355), and smn-1(ok355);daf-2(e1370) mutant animals at 20°C. Smn-1(ok355);daf-2(e1370) homozygotes live significantly 30% longer than smn-1(ok355) mutant animals (p < 0.0001, Log-rank test; for additional details, see Extended Data Fig. 1-1). B, Lifespan analysis of N2, smn-1(rt248), and smn-1(rt248);daf-2(e1370) at 20°C. Smn-1(rt248);daf-2(e1370) homozygotes live significantly 40% longer than smn-1(ok355) mutant animals (p < 0.0001, Log-rank test). C, Quantitative analysis of smn-1 mRNA in wild-type N2, smn-1(ok355), and smn-1(ok355);daf-2(e1370) mutant animals at various developmental time points. qPCR (n = 3/timepoint/strain) measuring smn-1 mRNA abundance normalized to tba-1 in indicated strains is shown in the y-axis. Levels of smn-1 mRNA in N2 animals gradually decrease from day 2 (D2) to day 10 (D10) after hatch. Levels of smn-1 mRNA in both smn-1(ok355) and smn-1(ok355);daf-2(e1370) mutant animals were barely detectable (<1.0% of smn-1 mRNA in N2). The bar graph represents mean ± SEM from three independent experiments. Chia-Yen Wu et al. eNeuro 2018;5:ENEURO.0289-18.2018 ©2018 by Society for Neuroscience