Reactive oxygen species (ROS), including superoxide (O2−·), hydrogen peroxide (H2O2), and hydroxyl radical, is important cellular toxicants that generated as products or by‐products in cells. A series of antioxidant mechanisms maintain intracellular redox homeostasis. When they deficit, overproduction of ROS causes DNA mutations and protein dysfunction, which eventually leads to cell injury and aging. The thiomethyl group that exists on the surface exposed methionine (Met) residues has been recognized as a key endogenous antioxidant defense (Ruan et al., 2002; Davies, 2005; Wood et al., 2009; Kim, 2013), providing for efficient scavenging of oxidants. To maintain the effective content of Met (Ruan et al., 2002), methionine sulfoxide reductase A (MsrA) plays a central role. MsrA reduced the oxidate of Met (methionine sulfoxide, MetO) back to Met and increased resistance of organisms to oxidative stress (Weissbach et al., 2002; Koc et al., 2004). Interestingly, MsrA was previously reported as a regulator of lifespan to increase longevity in animals, including Drosophila, yeast, and mice (Ruan et al., 2002; Koc et al., 2004; Chung et al., 2010). Gene expression decreased for MsrA in senescent cells and aged animals (Gabbita et al., 1999; Oien et al., 2009), and this decline was associated with the accumulation of oxidized proteins during aging. 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). Thus, pharmacological enhancement of MsrA function seems to be reasonable therapeutic strategy against aging in clinics. Only very few approaches are available to enhance MsrA function, such as activators like fusaricidin (Cudic et al., 2016), substrates including L‐Met and S‐methyl‐L‐cysteine (Wassef et al., 2007; Wood et al., 2009), and upregulation of endogenous MsrA (Novoselov et al., 2010; Wu et al., 2013a).