The balance of free radicals and antioxidants plays a critical role in life. Reactive oxygen and nitrogen intermediates are generated from normal cellular processes as well as in certain pathological states, which could fulfill essential biological functions but also elicit serious threat to health. Numerous diseases are now identified to be related to oxidative stress caused by insufficient antioxidant defense. A central paradigm of my research is to study how this delicate balance could be affected by rigorous physical activity, during aging and in some diseases. There is strong evidence that moderate levels of exercise combined with proper nutrition are essential for health and longevity. I have been fortunate to be able to conduct research in this exciting field of biological science during the past 25 years. Moving my laboratory to the University of Minnesota opens new opportunities and I am looking forward to working together with graduate and undergraduate students and collaborating with faculty and researchers across campus.
Exercise and Nutrition Are Medicine
Strenuous exercise is associated with increased oxygen consumption and free radical production. Tissues actively involved in exercise, such as skeletal muscle, liver and heart, are exposed to an increased oxidative challenge. Yet, serious damages to these tissue due to exercise are rare because organisms are capable of adapting to elevated levels of free radicals by increasing antioxidant defense. In fact, some reactive oxygen and nitrogen species (such as hydrogen peroxide and nitric oxide) can serve as signaling molecules to active the adaptive processes. Nutrition serves a critical role in this paradigm as deficiency of essential antioxidant nutrients renders the body to high risks of oxidative damage, whereas supplementation of certain antioxidants offer increased protection. However, overload of exogenous antioxidants could backfire by offsetting natural adaptive response and removing exercise benefits. Selective supplementation of a broad spectrum of phytochemicals has proven to be a smart way to enhance antioxidant protection while avoiding depletion of “good” reactive species.
Free Radicals, Antioxidants and Aging
There is strong evidence that aging is caused by free radical reaction with the cellular components of human body throughout the life. Increased free radical generation and subsequent modification of the macromolecules underlie many age-related degenerated problems such as sarcopenia, Alzheimer diseases, cardiopulmonary disorders and cancer. One of my strong interests is to seek physiological and nutritional strategies that could enhance antioxidant defense and prevent age-related health deterioration. We use both animal and human subjects to study mechanisms causing these problems and to explore strategies to benefit older people. We emphasize regular physical activity that has been shown to enhance antioxidant defense and maintenance of proper nutritional intake throughout the life span.
Kang, C., D. Yeo, L. L. Ji. Muscle Immobilization Activates Mitochondrial Autophagy and Disrupt Mitochondrial Dynamics. Acta Physiol. (2016. doi:10.1111/apha. 12690)
Powers, S. P., Z. Radak, L. L. Ji. Exercise-induced oxidative stress: A look backward and a look to the future. J. Physiol (London). (2016, http://dx.doi.org: 10.1113/JP270646)
Ji, L. L., C. Kang and Y. Zhang. Exercise-induced hormesis and skeletal muscle health. Free Rad. Biol. Med. 98:113-122, 2016. (2016, http://dx.doi.org / 10.1016/j.freeradbiomed.2016.02.025)
Kang, C. and L. L. Ji. PGC-1α Over-expression via local transfection attenuates mitophagy pathway in muscle disuse atrophy. Free Rad. Biol. Med. 93:32-40, 2016.
Li, H., W. Miao, J. Ma, Z. Xu, H. Bo, L. L. Ji, Y. Zhang. Mitochondrial stress triggers inflammatory response of myocardium via NLRP3 inflammasome activation during acute exercise. Oxid. Med. Cell. Longev. (Volume 2016, Article ID 1987149, http://dx.doi.org / 10.1155/2016/1987149)
Koenig, R, J. Dickman, C. Kang, and L. L. Ji. Avenathranmide Supplementation Attenuate Eccentric Exercise-induced Inflammation and Oxidative Stress in Young Women. Eur. J. Appl. Physiol. 116: 67-76, 2016.
Kang, C., C.A. Goodman, T. A. Hornberger, L. L. Ji. PGC-1α Over-expression by in vivo Transfection Attenuates Mitochondrial Deterioration of Skeletal Muscle Caused by Immobilization. FASEB J. 29:4092-2015.
Ji, L.L and C. Kang. Role of PGC-1α in the Etiology of Sarcopenia. Gerontol. 61: 139-148, 2015.
Song C, Zhang JW, Bo H, Ji LL, Zhang Y. The effect of concentric exercise on anti-inflammation of interleukin-6 in skeletal muscle. Chin. J. Sports Med. 34(4):329-333, 2015.
Bo, H., W. Kang, H. Li, X. Wang, L. L. Ji, Y. Zhang. Exercise-induced neuroprotection of hippocampus in APP/PS1 transgenic mice via upregulation of mitochondrial 8-oxoguanine DNA glycosylase, Oxid. Med. Cell. Longev. (dx.doi:10.1155/2014/834502 Epub 2014)
Bo H, Jiang N, Zhang ZY, Ji LL, Zhang Y. Exercise and Health: From evaluation of health promoting effect exercise to exploration of exercise minetics. Progr. Physiol. Sci.. 45(4):251-256, 2014.
Koenig, R., J. R. Dickman, C. Kang, T. Zhang, Y-F. Chu, L. L. J. Avenanthramide Supplementation Attenuates Exercise-induced Inflammation in Postmenopausal Women. Nutrition J. 13:21-31, 2014.
Ji, L. L. and Y. Zhang. Antioxidant and anti-inflammatory effects of exercise: role of redox signaling. Free Rad. Res. 48:3-11, 2014.
Jiang N, Bo H, Song C, Guo J, Zhao F, Feng H, Ding H, Ji LL, Zhang Y. Increased vulnerability with aging to MPTP: the mechanisms underlying mitochondrial dynamics. Neurol. Res. 2013, (DOI 10.1179/1743132813Y.0000000296 ner3319.3d)
Kang, C. and L. L. Ji. Muscle immobilization and remobilization downregulates PGC-1 signaling and the mitochondrial biogenesis pathway. J. Appl. Physiol. 115: 1618-1625, 2013.
Kang, C., E. Chung, and L. L. Ji. Exercise training stimulates PGC-1 and mitochondrial biogenic pathway in skeletal muscle of aged rats. Exp. Gerontol. 48: 1343-1350, 2013.
Bo H, Jiang N, Ji LL, Zhang Y. Mitochondrial Redox Metabolism in Aging: Effect of Exercise Interventions. J. Sport Health Sci. 2:67-74, 2013.
Ji, L. L. Healthy aging: Cellular insights. J. Sport Health Sci. 2:65-66, 2013.
Kang C, L. L. Ji. Role of PGC-1a in muscle function and aging: Review. J. Sport Health Sci. 2:81-86, 2013.
Feng, H., C. Kang, J. R. Dickman, R. Koenig, Awoyinka, Y. Zhang and L. L. Ji. Training-induced mitochondrial adaptation: role of peroxisome proliferator-activated receptor ? coactivator-1a, nuclear factor-?B and ß-blockade. Exp. Physiol. 98:784-95, 2013.
Sakurai T, O. Kashimura, Y. Kano, H. Ohno, T.Izawa, L. L. Ji, T. M. Best. Role of nitric oxide in muscle regeneration following eccentric muscle contractions in rat skeletal muscle. J. Physiol. Sci. 63:263-270, 2013.
J. Zhao, Y. Tian, J. Cao, L. Jin, L. L. Ji. Mechanism of endurance training-induced erythrocyte deformability in rats involves erythropoiesis. Clin. Hemorheol. Microcirc. 53: 257-66, 2013.
Bao H, Wang X, Chen QY, Ji LL, Zhang Y. Endurance Exercise Affects the Mitochondrial ROS Generation during Aged Muscle Satellite Cells Differentiation. Chin. J. Sport Med. 31:475-482, 2012.
Kang, C and L. L. Ji. Role of PGC-1a Signaling in Skeletal Muscle Health and Disease. Ann. N.Y. Acad. Sci. 1271:110-7, 2012.
Bolling, B. W., L. L. Ji, C-H. Lee, and K. L. Parkin. Dietary supplementation of ferulic acid and 1 ferulic acid ethyl ester induces quinone reductase and glutathione-S-transferase in rats. Food Chem. 124: 1-6, 2011.
Liu T, Zhang M, Xu D, Liu SS, Ji LL, Zhang Y. Exercise training enhances mitochondrial biogenesis and cardiac remodeling in rats with heart failure induced by myocardial infarction. Chin. J. Sports Med. 30: 260-2662, 2011.
Finley, J.W., Kong, A.N., Hintze, K.J., Jeffery, E.H., Ji, Li L., Lei, X.G. Antioxidants in the food supply: The current state of the science and the need for the food industry to update its message to the public. J. Agr. Food Chem. 59:6837-46, 2011.
Koenig, R., J. Dickman and L. L. Ji. Avenanthramides are Bioavailable and Accumulate in Hepatic, Cardiac, and Skeletal Muscle Tissue following Oral Gavage in Rats. J. Agr. Food Chem. 59:6438-43, 2011.
Han YM, Liu ZQ, Chang YX, Liu SS, Ji LL, Zhang Y. Effect of Aerobic Endurance Training on Mitochondrial Biogenesis of Skeletal Muscle in Aging Rats. Chin. J. Sports Med. 29: 425-429, 2010.
Bo H, Y. Zhang, L.L. Ji. Redefining the Role of Mitochondria in Exercise: a Dynamic Remodeling. Ann. N. Y. Aca. Sci. 1201: 121-128, 2010.
Liao P, J. P. Zhou, L. L. Ji. and Y. Zhang, Lengthening Contraction Induced Inflammatory Responses in Rat Skeletal Muscle: Role of Tumor Necrosis Factor-a. Am. J. Physiol.(Reg. Integr. Comp. Physiol.) 298: R599-607, 2010.
Ji L. L. , J. R. Dickman, C. Kang, and R. Koenig. Exercise-induced Hormesis may help healthy aging. Dose-Response 28: 73-79, 2010.
Ding H,, N. Jiang, H. Liu, X. Liu, D. Liu, F. Zhao, L. Wen, S. Liu , L. L. Ji, Yong, Zhang. Dynamic Response of mitochondrial fusion and fission protein gene expression to exercise in rat dkeletal muscle. Biochim. Biophys. Acta 1800: 250-256, 2010.
Ji L. L. and Zhang, Y. Antioxidant signaling in skeletal muscle. In Muscle Plasticity-Advances in Biochemical and Physiological Research. (Editor. J. Magalhaes and Antonio Ascensão). Research Signpost, p. 95-120, 2009.
Dickman, J. R., R.T. Koenig, and L. L. Ji. American ginseng supplementation induces a mild oxidative stress in elderly women. J. Am. Coll. Nutr. 28:219-228, 2009.
Kang C., K. M. O’Moore, J. R. Dickman and L. L. Ji. Exercise activation of muscle peroxisome proliferator-activated receptor-? coactivator-1a signaling is redox sensitive. Free Rad. Biol. Med. 47: 1394-1400, 2009.
Ji L. L. M-C. Gomez-Cabrera, and J. Vina. Role of Antioxidants in Muscle Health and Pathology. Infectious Disorders Special Issue. Infect. Disord. Drug Targets 9(4):428-444, 2009.
Jiang, N.; Zhang, G.; Bo, H.; Qu, J.; Ma, Cao.; D, Wen, L.; Liu, S.; Ji, L.L.; Zhang, Y. Upregulation of uncoupling protein-3 in skeletal muscle during exercise: a potential antioxidant function. Free Rad Biol Med 46:138-145, 2009
Ji L. L. and R. Koenig. Oat antioxidant. In Nutrigenomics and Proteomics in Health and Disease. (Ed. Y. Mine). CRC-Taylor & Francis, New York. P. 239-249, 2008.
Ji L. L. Z. Radak, and S. Goto. Exercise and hormesis: How the Cell Copes with Oxidative Stress. Am. J. Pharmacol. Toxicol. 3 (1): 41-55, 2008.
Bo H., N. Jiang, G. Ma, J. Qu, G. Zhang, D. Cao, L. Wen, S. Liu, L. L. Ji, and Y. Zhang. Regulation of mitochondrial uncoupling respiration during exercise in rat heart: role of ROS and uncoupling protein-2. Free Rad. Biol. Med. 44: 1373–1381, 2008.
Ji L. L. Modulation of skeletal muscle antioxidant defense by exercise: role of redox signaling. Free Rad. Biol. Med. 44: 142-152, 2008.
Ji L. L. Physical Activity: A Strong Stimulant for Hormesis during Aging. In Mild Stress and Healthy Aging: Applying Hormesis. Ed. Eric. Le Bourg and Suresh Rattan. SPI Publishing, p. 97-114, 2007.
Ji L. L., M.C. Gomez-Cabrera and J. Vina. Role of nuclear factor ?B and mitogen-activated protein kinase signaling in exercise-induced antioxidant enzyme adaptation. Appl. Physiol. Nutr. Metabol. 5:930-935, 2007.
Larraín, R. E., M. P. Richards, D. M. Schaefer, L. L. Ji, and J. D. Reed. Growth performance and muscle oxidation in rats fed increasing amounts of high-tannin sorghum. J. Animal Sci. 85:3276-3284, 2007.
L. L. Antioxidant signaling in skeletal muscle: a brief review. Exp. Gerontol. 42: 582-593, 2007.
L. L. Oxidative Stress and Antioxidant defenses: effects of aging and exercise. In: Oxidative stress, Exercise and Aging. (Ed. H. M. Allesio and A. E. Hagerman). Imperial College Press, London. P. 85-109, 2006.
L. L., M-C. Gomez-Cabrera and J. Vina. Exercise and hormesis: Activation of cellular signaling pathways. Ann. N. Y. Acad. Sci. 1067:425-435, 2006.
, C-H., M. Wettasinghe, B. W. Bolling, L. L. Ji and K. Parkin. Betalains as markers for highly-enriched phase II enzyme-inducing components from red beetroot (Beta vulgaris L.) extracts. Nutr. Cancer 53:91-103, 2005.
urai T, J. Hollander, S. Brickson, T. Izawa, H. Ohno, L. L. Ji, and T. M. Best. 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, 2005
ez-Cabrera, M-C, C. Borras, G. Santangelo, F.V. Pallardó , J. Sastre, L. L. Ji and J. Vina. Decreasing xanthine oxidase mediated oxidative stress prevents useful cellular adatptations to exercise in rats. J. Physiol. (London) 567:113-120, 2005.
L. L., M-C. Gomez-Cabrera, N. Steinhafel, and J. Vina. Acute Exercise Activates Nuclear Factor (NF) kB Signaling Pathway in Rat Skeletal Muscle. FASEB J. 18:1499-1506, 2004.
L. L. and D. Perterson. Aging, Exercise and Phytochemicals: Promises and Pitfalls. Ann. N.Y. Acad. Sci. 1019: 453-461, 2004.
L. L. Free radicals and heart ischemia-reperfusion injury. In: Exercise and Diseases (Ed. Z. Radak) Human Kinetics Publisher, Champaign, IL. p. 110-132, 2004.
alakrishnan, A. L. L. Ji and C. Cirelli. Effect of sleep deprivation on markers of oxidative stress and cellular damage. Sleep 27: 27-35, 2004
ez-Cabrera, M. C., F.Sanchis-Gomar, V. E. Martinez-Bello, S. Ibanez-Sania, A. L. Nascimento, L. L. Ji and J. Vina. Exercise as a model to study oxidative stress. In Oxidative Stress in Basic Research and Clinical Practice-Experimental Models (Eds. Samar Basu and Lars Wiklund). Human Press/Springer Science, Uppsala, Sweden (in press)
L. Li. Metabolic and antioxidant adaptation to exercise: role of redox signaling. In: Nutrition, Exercise, Epigenetics: Aging Interventions (B. P. Yu, Ed.) Springer International Publishing, Switzerland, 2015. DOI 10.1007/978-3-319-14830-4_6)
L. L. Oxidative Stress Response Pathways: Role of Redox Signaling. In: Hormesis in Human Health and Disease (S. Rattan and E. LeBourg, Eds.). CRC Press, p. 282-304, 2014.
L. L. Antioxidant Signaling: Role of Mitochondria. In Systems Biology of Free Radicals and Anti-Oxidants (Ed. Laher I). Springer-Verlag, Germany 195:1-22, 2013.