Figure 3. mrps-5 RNAi prevents aging-associated functional decline and alters mitochondrial function.

a, Knockdown of mrpl-1, mrpl-2 or mrpl-37 increased lifespan by 57%, 54%, or 41%, respectively. b, When RNAi of mrps-5 was performed during the larval stages only, lifespan increased by 48%, while RNAi started from the L4 stage had no effect. p≤0.001 is for larval-only versus either vector control or adult-only. c, mrps-5 or cco-1 RNAi prevented age-related changes in muscle morphology as evidenced by a p_myo-3MYO-3::GFP reporter worm highlighting myosin heavy chain. d, mrp RNAi in C. elegans decreased respiration. Respiration/worm is shown here, but respiration was similarly decreased when corrected for protein. FCCP was added at the indicated time. Values are mean±SEM (n=10), *** p≤0.001. e–g, mrps-5 RNAi decreased ATP levels (e, n=3), citrate synthase activity (f, n=3), and altered the ratio between nDNA (ATP5A) versus mtDNA-encoded (MTCO1) OXPHOS proteins, similar to cco-1, but not mev-1 (g, n=4). * p≤0.05. h, mrps-5 RNAi resulted in fragmented mitochondria, as visualized using the p_myo-3::mito::GFP reporter, which expresses mitochondria-targeted GFP driven by the muscle-specific myo-3 promoter. i, mrps-5 RNAi increased mean lifespan by 40%. j-m, mrps-5 RNAi extends lifespan of daf-16(mu86) (j), sir-2.1(ok434) (k), aak-2(ok524) (l), mev-1(kn1) (m) mutants by 37%, 40%, 69%, 112%. n, Knockdown of cco-1 does not extend lifespan of mrps-5 RNAi worms. See Supplementary Table 2 and Fig. 4.