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Lack of methionine sulfoxide reductase A in mice increases sensitivity to oxidative stress but does not diminish life span

Adam B. Salmon^*,1, Viviana I. Pérez^*,,1, Alex Bokov^*,, Amanda Jernigan^*, Geumsoo Kim, Hang Zhao, Rodney L. Levine and Arlan Richardson^*,,||,2

^* The Sam and Ann Barshop Institute for Longevity and Aging Studies,

Department of Cellular and Structural Biology, and

Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA;

Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA; and

^|| The Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas, USA

² Correspondence: Department of Cellular and Structural Biology, The Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 15355 Lambda Dr., San Antonio, TX 78245-3207, USA. E-mail: richardsona{at}uthscsa.edu

Methionine sulfoxide reductase A (MsrA) repairs oxidized methionine residues within proteins and may also function as a general antioxidant. Previous reports have suggested that modulation of MsrA in mice and mammalian cell culture can affect the accumulation of oxidized proteins and may regulate resistance to oxidative stress. Thus, under the oxidative stress theory of aging, these results would predict that MsrA regulates the aging process in mammals. We show here that MsrA^–/– mice are more susceptible to oxidative stress induced by paraquat. Skin-derived fibroblasts do not express MsrA, but fibroblasts cultured from MsrA^–/– mice were, nevertheless, also more susceptible to killing by various oxidative stresses. In contrast to previous reports, we find no evidence for neuromuscular dysfunction in MsrA^–/– mice in either young adult or in older animals. Most important, we found no difference between MsrA^–/– and control mice in either their median or maximum life span. Thus, our results show that MsrA regulates sensitivity to oxidative stress in mice but has no effect on aging, as determined by life span.—Salmon, A. B., Pérez, V. I., Bokov, A., Jernigan, A., Kim, G., Zhao, H., Levine, R. L., Richardson, A. Lack of methionine sulfoxide reductase A in mice increases sensitivity to oxidative stress but does not diminish life span.

Key Words: longevity • free radical • stress resistance • aging • antioxidant