Extended Data Fig. 2: Survival data of animals from the lifespan, tissue collection and phenotyping cohorts.

Survival curves of a–c female and d–f male mice of the a, d lifespan, b, e tissue collection and c, f phenotyping cohort. The corresponding pooled data are presented in Fig. 2. (Sample size lifespan cohort: control ♂ n = 52, ♀ n = 52, rapamycin ♂ n = 52, ♀ n = 51, trametinib ♂ n = 52, ♀ n = 51, combined ♂ n = 51, ♀ n = 51; tissue collection cohort: control ♂ n = 53, ♀ n = 33, rapamycin ♂ n = 53, ♀ n = 32, trametinib ♂ n = 54, ♀ n = 32, combined ♂ n = 54, ♀ n = 32; phenotyping cohort n = 15 for all treatments). Trametinib significantly extended lifespan in male mice and the combined treatment significantly increased lifespan compared to the individual drug treatments in both males and females when only survival of the lifespan cohort was analyzed. In the female lifespan cohort, trametinib showed a similar trend but the effect on lifespan was not significant, due to the limited power of the smaller sample size (females lifespan cohort: control vs rapa p < 0,0001, control vs tram p < 0.0697, control vs rapa/tram p < 0,0001, rapa vs tram p = 0.0005, rapa vs rapa/tram p = 0.0004, tram vs rapa/tram p < 0.0001; males lifespan cohort: control vs rapa p < 0,0001, control vs tram p = 0,0020, control vs rapa/tram p < 0,0001, rapa vs tram p = 0.1799, rapa vs rapa/tram p = 0.0283, tram vs rapa/tram p = 0.0006, log rank test). Survival curves for control and rapamycin treated mice of the lifespan cohort were previously published22. Within the different cohorts all treatments were run in parallel.