To confirm that MsrA involved in the mechanism of DMS‐mediated longevity, the level of MsrA was downregulated by UAS‐GAL4 system (Fig. S7A). As shown in Fig. 5G, DMS failed to prolong the lifespan in MsrA RNAi group, indicating that the lifespan extension effect of DMS is dependent on MsrA activity. Then, we used feeding RNAi (F43E2.5 plasmid) to decrease the msra‐1 expression to 10 ± 5% of control group (L4440 plasmid) in C. elegans (Fig. S7B). In msra‐1 RNAi group, lifespan was significantly shortened from 22.5 ± 0.8 day to 17.8 ± 0.6 day, which suggested that MsrA plays a critical role. DMS (10 μm) could not extend lifespan in msra‐1 RNAi group (Fig. 5H). Thus, MsrA was required in the effect of DMS on worm longevity.