Fig. 6. ATF-4 is essential for longevity from reduced mTORC1 activity.

a Inhibition of mTORC1 by either raga-1 or ragc-1 knockdown led to preferential translation of ATF-4. RNAi treatments were initiated at the L4 stage, with GFP intensity scored at day 3 of adulthood. b Inhibition of mTORC1 or mTORC2 by knockdown of ragc-1 or rict-1, respectively, leads to preferential translation of ATF-4. Similar effects were observed in WT and eif-2α(qd338) mutants. c Post-development knockdown of raga-1 or rict-1 extends lifespan in both WT and eif-2α(qd338) mutants. d Mutation in raga-1 increases lifespan in an atf-4-dependent manner. e Reducing mTORC1 signalling by adulthood specific raga-1 knockdown improves healthspan dependent upon atf-4, as assessed by pharyngeal pumping rate. Mean ± S.E.M. P values relative to WT of the corresponding day with One-way ANOVA with post hoc Dunnett’s multiple comparisons test. f Adult-specific knockdown raga-1 increases oxidative stress resistance (2 mM tert-butyl hydrogen peroxide (tBOOH)) in an atf-4-dependent manner. RNAi was started at the L4 stage, and stress resistance was measured at day 3 of adulthood with the lifespan machine (See Supplementary Data 10 for details). g Rapamycin treatment during adulthood extends lifespan independently of atf-4. h Adult-specific knockdown of the mTORC2 subunit rict-1 extends lifespan in an atf-4-dependent manner. i Adult-specific inactivation of both mTORC1 and mTORC2 increases lifespan independently of atf-4. For statistical details and additional trials in (a), (b), see Supplementary Data 9. For statistical details and additional lifespan trials in (c), (d), (g)-(i), see Supplementary Data 1.