MsrA deficiency has been involved in the pathophysiology of aging‐related diseases (Yermolaieva et al., 2004; Pal et al., 2007; Oien et al., 2008; Prentice et al., 2008). Previous study has reported that msra‐1 absence decreases median survival of long‐lived daf‐2 worms (Minniti et al., 2009). In our study, lifespan in msra‐1 RNAi group was significantly shortened from 22.5 ± 0.8 day to 17.8 ± 0.6 day, indicating that MsrA plays a critical role in lifespan of worms (Fig. 5H). In flies, reducing MsrA activity exhibited little effect on the lifespan. It seems that the role of MsrA in lifespan is conditionally important in response to certain stresses. As a catalytic antioxidant, under MsrA deficiency, the organism may be vulnerable to stress and other compensatory mechanisms may be activated to alleviate its effect on lifespan. Enhancement of MsrA system may be beneficial for lifespan by reducing accumulated oxidative damage, as previous reports have revealed that upregulation of MsrA system increases longevity in animals, including Drosophila and yeast (Ruan et al., 2002; Koc et al., 2004; Chung et al., 2010). Only very few approaches are available to enhance MsrA function, such as activators like fusaricidin (Cudic et al., 2016), supplement of its substrates (Wassef et al., 2007; Wood et al., 2009), and upregulation of endogenous MsrA (Novoselov et al., 2010; Wu et al., 2013a).One remarkable finding of the present study is that food supplement of DMS extended the lifespan of C. elegans and Drosophila via an MsrA‐dependent manner and improves the life condition under oxidative stress. These results support the connection between our observed effects on longevity and antioxidant‐mediated cytoprotective mechanisms. However, other multiple mechanisms may be involved in the effect of DMS on the ROS profile, such as alterations in metabolism and gene expression. Considering the low‐molecular weight, endogenous origin, and easy preparation, it is possible that supplement of DMS‐rich and methyl sulfide‐rich foods including beer, cheese, and marine products may serve as a potential nutritional strategy to enhance MsrA function and prevent aging.