MsrA knockdown abolishes the cytoprotective effect and longevity benefits of DMS. PC12 cells were transfected with control shRNA (A) or MsrA shRNA (C). The transfected cells were pretreated with or without DMS (5 μm for 30 min) and then incubated with AA (100 μg mL−1 for 30 min). (B, D) The release of superoxide was determined by the MitoSOX red fluorescence. n = 6, Student's t‐test, ## P < 0.01 vs. control, **P < 0.01 vs. AA. The scale bar represents 50 μm. (E‐F) The H2O2 (250 μm, 12 h) was introduced into the culture medium after treatment with DMS (5 μm for 30 min). (E) The cell survival rates were measured with MTT test (n = 8, Student's t‐test, ## P < 0.01 vs. control, **P < 0.01 vs. H2O2). (F) MDA contents in cultured cells were measured (n = 8, Student's t‐test, ## P < 0.01 vs. control, **P < 0.01 vs. H2O2). (G) Lifespan analyses of control flies and dMsrA RNAi flies (n = 400, log‐rank post hoc Kaplan–Meier survival analysis, P > 0.05 vs. UAS‐GAL4). (H) Lifespan analyses of control worms (L4440) and F43E2.5 (msra‐1 RNAi) worms (n = 60, log‐rank post hoc Kaplan–Meier survival analysis, P > 0.05 vs. L4440). (I) Survival rates of worms (5‐day‐old adult) in each group were evaluated after 3 h in S‐basal buffer containing H2O2 (10 mm) in 20 °C (n = 60 from three independent tests, Student's t‐test, **P < 0.01 vs. control RNAi).