Fig. 3: LIN-39 promotes longevity under reduced IIS from the nervous system and exclusively during later larval development.

a Kaplan–Meier survival estimates with 95% confidence intervals for daf-2(e1370) mutant C. elegans with functional RNAi in either the whole body or the indicated tissues, grown on the indicated RNAi bacteria. (n = 83 (whole body; control RNAi), 151 (whole body; lin-39 RNAi), 125 (hypodermis; control RNAi), 124 (hypodermis; lin-39 RNAi), 291 (intestine; control RNAi), 264 (intestine; lin-39 RNAi), 94 (muscle; control RNAi), 69 (muscle; lin-39 RNAi), 174 (neurons; control RNAi), 142 (neurons; lin-39 RNAi); for results from a second independent biological replicate experiment, see Supplementary Table S11). b Kaplan–Meier survival estimates with 95% confidence intervals for daf-2(e1370); sid-1(pk3321) mutant C. elegans, in which sid-1 was reconstituted only in the nervous system, resulting in neuron-specific RNAi. Animals were grown on the indicated RNAi bacteria either throughout life, exclusively during development (and then shifted to dcr-1 RNAi during adulthood to inactivate the RNAi), or exclusively during adulthood (after having been grown on HT115 bacteria during development). (n = 118 (throughout life; control RNAi), 248 (throughout life; lin-39 RNAi), 215 (only development; control RNAi), 233 (only development; lin-39 RNAi), 121 (only adulthood; control RNAi), 134 (only adulthood; lin-39 RNAi); for independent replication of these findings, see Fig. 3c and Supplementary Table S12). c Same experimental setup as under (b), but more knockdown-windows were tested. Results are displayed as an UpSet plot showing the changes in median lifespan induced by neuron-specific lin-39 knockdown. For conditions tested in multiple experiments, percentages were averaged. These included development (3 independent experiments), adulthood (2 independent experiments), and throughout life (2 independent experiments). The actual survival curves are shown in (b) and Supplementary Fig. S4b. (for n, see Supplementary Table S12; the experiment in conjunction with Fig. 3b provides internal biological replication of the key findings due to overlapping or matching knockdown windows). Boxes state changes in median lifespan and the associated p-values (based on two-sided log-rank tests) for the indicated comparisons. Source data are provided as a Source Data file.