FREE RADICAL GENERATION AND ANTIOXIDANT RESPONSE DURING AGING
Aging has been proposed to be a result of continuous reactions of cell components with oxygen free radicals throughout the life span. This Free Radical Theory of Aging has received increasing support in the past decade, and mounting evidence now relates some fundamental physiological, biochemical and pathological alterations in the body with free radical generation during the aging process.
Our effort in studying the relationship between free radical chemistry and aging is three-fold. First, we intend to assess the level of free radical generation in aged tissues using reliable and convenient method, and to delineate age-related oxidative changes in various tissues and organs, such as lipid peroxidation, cellular redox status, mitochondrial dysfunction, and specific enzyme systems. Second, we are interested in the response, regulation and adaptation of the cellular enzymatic and nonenzymatic antioxidants during aging. For example, we have investigated the role of glutathione in protecting age-related oxidative stress in the heart and skeletal muscle. A major focus at present is the gene regulation and cell signaling of antioxidant enzymes in aging muscle. Third, because cellular and whole-body nutritional status has an important impact on the antioxidant systems, we are conducting research using dietary intervention and supplementation of phytochemicals such as oats and ginseng, hoping to provide insights into nutritional strategies in the aging population.
As an exercise physiologist, I am particularly interested in the impact of acute and chronic exercise on the relationship between free radical generation and aging. Preliminary evidence suggests that exercise responses in senescent organs and tissues are quite different from those of the young ones. We need yet to develop strategies that are suitable for the aged population to participate in exercise programs, in order to avoid detrimental effects of free radical production whereas the benefits of exercise can be maximized.
My research program is located in the Biodynamics Laboratory, a facility dedicated to studying the physiological, biochemical and molecular aspects of physical exercise. With the state-of-the-art equipment and collaborations across the campus, we take a multidisciplinary approach to integrate research related to aging, nutrition, exercise and health.
Representative Publications Dickman, J.R., Koenig, R.T., & Ji, L.L. (In Press)American ginseng supplementation induces a mild oxidative stress in elderly women. Am. J. Clin. Nutr.
Ji, L.L. (In Press)Oxidative stress. In F.C. Mooren & J.S. Skinner (Eds.), Encyclopedia of exercise medicine in health and disease. Heidelberg, Germany: Springer Publishers. Available in September, 2010.
Jiang, N., Zhang, G., Bo, H., Qu, J., Ma, Cao., D, Wen, L., Liu, S., Ji, L.L., & Zhang, Y. (In Press)Upregulation of uncoupling protein-3 in skeletal muscle during exercise: A potential antioxidant function. Free Rad. Biol. Med.
Ji, L.L., Koenig, R., & Wise, M. (2008). Oat antioxidant. In Y. Mine (Ed.), Nutrigenomics and proteomics in health and disease. New York: CRC-Taylor & Francis. (in press).
Ji, L.L. (2008). Modulation of skeletal muscle antioxidant defense by exercise: Role of redox signaling. Free Rad. Biol. Med., 44, 142-152.
Ji, L.L., Diffee, G., & Schrage, W. (2008). Challenges in exercise physiology research and education. Quest, 60, 13-18.
Bo, H., Jiang, N., Ma, G., Qu, J., Zhang, G., Cao, D., Wen, L., Liu, S., Ji, L.L., & Zhang, Y. (2008). Regulation of mitochondrial uncoupling respiration during exercise in rat heart: Role of ROS and uncoupling protein-2. Free Rad. Biol. Med, 44, 1373–1381.
Ding, H., Liu, X., Liu, D., Wen, L., Liu, S., Ji, L.L., & Zhang, Y. (2008). Acute exercise induces skeletal muscle mitochondrial biogenesis in rat: H2O2 is involved in contractile activity-induced PGC-1α transcriptional up-regulation. Chin. J. Sports Med., 27, 136-143.
Ji, L.L., Radak, Z., & Goto, S. (2008). Exercise and hormesis: How the cell copes with oxidative stress. Am. J. Pharmacol. Toxicology, 3(1), 41-55.
Ji, L.L. (2007). Antioxidant signaling in skeletal muscle: a brief review. Exp. Gerontol., 42(7), 582-93.
Ji, L.L. (2007). Physical activity: A strong stimulant for hormesis during aging. In E. Le Bourg & S. Rattan (Eds.), Mild stress and healthy aging: Applying hormesis (pp. 97-114). SPI Publishing.
Ji, L.L., Gomez-Cabrera, M,-C., & Vina, J. (2006). Exercise and hormesis: Activation of cellular signaling pathways. Ann. N.Y. Acad. Sci., 1067, 425-435.
Gomez-Cabrera, M.-C., Domenech, C.E., Ji, L.L., & Vina, J. (2006). Exercise as an antioxidant: It up-regulates important enzymes for cell adaptation to exercise. Sci. Sports., 21, 85-89.
Ji, L.L. (2006). Oxidative stress and antioxidant defenses: Effects of aging and exercise In H.M. Allesio & A.E. Hagerman (Eds.), Oxidative stress, exercise and aging (pp. 85-109). London: Imperial College Press.
Lee, C.-H., Wettasinghe, M., Bolling, B.W., Ji, L.L., & Parkin, K. (2005). Betalains as markers for highly-enriched phase II enzyme-inducing components from red beetroot (Beta vulgaris L.) extracts. Nutr. Cancer, 53, 91-103.
Sakurai, T., Hollander, J., Brickson, S., Izawa, T., Ohno, H., Ji, L.L., & Best, T.M. (2005). Changes in nitric oxide and inducible nitric oxide synthase following stretch-induced injury to the tibialis anterio muscle of rabbit. Japan J. Physiol., 55, 101-107.
Gomez-Cabrera, M.-C., Borras, C., Santangelo, G., Pallardó, F.V., Sastre, J., Ji, L.L., Vina, J. (2005). Decreasing xanthine oxidase mediated oxidative stress prevents useful cellular adatptations to exercise in rats. J. Physiol., 567, 113-120.
Ji, L.L. (2004). Free radicals and heart ischemia-reperfusion injury. In Z. Radak (Ed.), Exercise and diseases (pp. 110-132). Champaign, IL: Human Kinetics Publisher.
Ji, L.L. (2004). Aging, exercise and phytochemicals: Promises and pitfalls. Ann. N.Y. Acad. Sci., 1019, 453-461.
Ji, L.L., Gomez-Cabrera, M.-C., Steinhafel, N., & Vina, J. (2004). Acute exercise activates nuclear factor (NF) kB signaling pathway in rat skeletal muscle. FASEB J., 18, 1499-1506.
Gopalakrishnan, A., Ji, L.L., & Cirelli, C. (2004). Effect of sleep deprivation on markers of oxidative stress and cellular damage. Sleep, 27, 27-35.
Tonkonogi, M., Walsh, B., Ji, L.L., Hammarqvist, O., Wernerman, J., & Sahlin, K. (2003). Reduced oxidative power but unchanged antioxidant capacity in skeletal muscle from aged humans. Pflug. Arch. (Eur. J. Physiol.), 446, 261-26.
Brickson, S., Ji, L.L., Schell, K., St. Pierre-Schneider, B., & Best, T.M. (2003). M1/70 attenuates blood-borne neutrophil oxidants, activation, and
myofiber damage following stretch injury. J. Appl. Physiol., 95, 969-76.
Ji, L.L., Lay, D., Chung, E., Fu, Y., & Peterson, D.M. (2003). Effects of avenanthramides on oxidant and antioxidant status in exercised rats. Nutr. Res., 23, 1579-1590.
Fu, Y., & Ji, L.L. (2003). Chronic ginseng consumption attenuates age-associated oxidative stress in rats. J. Nutr., 133, 3603-3609.
Okawara, T., Haga, S., Ha, S., Oh-Ishi, S., Toshinai. K., Kizaki, T., Ji, L.L., Suziki, K., & Ohno, H. (2003). Effects of endurance training on three superoxide dismutase
isoenzymes in human plasma. Free Rad. Res., 37, 713-719.
Ji, L.L. (2002). Exercise-induced modulation of antioxidant defense. Ann. N.Y. Acad. Sci., 959, 82-92.
Brickson, S., Corr, D.T., Hollander, J., Ji, L.L., & Best, T.M. (2001). Oxidant formation and immune response upregulation following muscle stretch injury in rabbit skeletal muscle. Med. Sci. Sport Exer., 33(12), 2010-2015.
Ramires, P., & Ji, L.L. (2001). Glutathione supplementation and training increases myocardial resistance to ischemia-reperfusion in vivo. Am. J. Physiol., 281, H679-H688.
Leichtweis, S., & Ji, L.L. (2001). Aging does not intensify ischemia-reperfusion injury in an intact heart: protection by glutathione. Mech. Age. Dev., 122, 503-518.
Hollander, J., Fiebig, R., Ookawara, T., Ohno, H., & Ji, L.L. (2001). Superoxide dismutate gene expression is activated by a single bout of exercise. Pflug. Arch. (Eur. J. Physiol.), 442, 426-434.
Hollander, H., Bejma, J., Ookawara, T., Ohno, H., & Ji, L.L. (2000). Superoxide dismutate gene expression: fiber specific effects of aging. Mech. Age. Dev., 116, 33-45.
Ji, L.L. (2000). Exercise at old age: Does it increase or alleviate oxidative stress? Ann. N.Y. Acad. Sci., 923, 236-247.
Ji, L.L., & Gore, M. (1998). Exercise. In B.P. Yu (Ed.), Methods in aging research (pp. 321-339). Boca Raton, FL: CRC Press.
Ji, L.L., Leeuwenburgh, C., Leichtweis, S., Fiebig, R., Hollander, J., Gore, M. & Bejma, J. (1998). Oxidative stress and aging: Role of exercise and its influences on antioxidant systems. Ann. N.Y. Acad. Sci., 845, 102-117.