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Leeuwenburgh, Christiaan, PhD

Published: March 15th, 2012

Category: Faculty, IOA Executive Board

Profile Picture

Title

Professor and Chief, Division of Biology of Aging

Institute on Aging

Leader, Metabolism and Biomarkers Core

Leader, Research Career Development Core

Address

2004 Mowry Road, Gainesville, Fl 32611

PO Box 100107, Gainesville, FL 32610.

E-mail

cleeuwen@ufl.edu

Phone

352-273-5735

Fax

352-294-5836

Education

1986-1988, BS, Applied Physiology, University of Florida
1988-1990, MS, Applied Physiology, University of Florida
1990-1995, PhD, Biochemistry and Aging, University of Illinois
1993-1995, Fellow, Biochemistry and Aging, University of Wisconsin
1995-1998, Post-Doc, Internal Medicine, Washington University School of Medicine Instructor Geriatrics & Gerontology

Appointments

Primary Appointment:
Department of Aging and Geriatric Research, Division of Biology of Aging
Institute on Aging

Affiliations:
Joint Faculty, Department of Anatomy and Cell Biology College of Medicine

Accomplishments

Dr. Leeuwenburgh is the Director of UF's Biochemistry of Aging Laboratory.  He has served as a Division Chief of the Biology of Aging and as the Core leader of the Genomics and Biomarkers Core of the Institute on Aging since its inception.  He has provided pivotal contribution to the successful award of the highly prestigious Claude Pepper Older Americans Independence Center (OAIC) by the National Institutes of Health (NIH). Only a few such Pepper OAICs are awarded nationwide.
Leeuwenburgh has received numerous research awards and grants, and his research has been published in more than 150 publications and presented at almost 50 conferences.

Professional Interests

Christiaan Leeuwenburgh's research interests are aging and mitochondrial biology.  Aging is thought to result from increased formations of reactive oxygen species and free radicals, mainly produced by the mitochondria, which can result in oxidative stress.
Mitochondria are organelles within cells that, when damaged, can have devastating effects on the body. When the mitochondria fail and become dysfunctional, they produce increasing amounts of reactive oxygen species (some are free radicals) and cells and tissue can be damaged and die. Reactive oxygen species are highly reactive molecules that cause damage to plasma membranes, enzymes, and DNA. Free radicals, unstable and potentially damaging molecules generated by the body's normal chemical reactions, may contribute to mitochondrial dysfunction and cell death, thereby accelerating diseases such as cardiovascular disease, diabetes, cancer, and Parkinson's disease.
Free radicals are unstable molecules because they possess one or more unpaired highly reactive electrons.These molecules can steal electrons from other molecules, thereby altering the structure. The molecule that loses an electron becomes oxidized. Oxidation is thought to damage tissues, including neurons, myocytes, and muscle cells. Normally, free radical damage is kept under control by antioxidants, compounds that protect cells from this damage.

Dr. Leeuwenburgh's research focuses on finding interventions that prevent the mitochondria from becoming dysfunctional.  His focus is on genetic, pharmacological and natural (specific diet and exercise) interventions.  For example, restricting the amount of calories older animals consume (or periodic fasting) has shown that these animals live 30 to 40% longer than animals not on a restricted diet and they produce less free radicals.
Leeuwenburgh says, for humans, studies have shown that people who participate in life-long exercise will, on average, live two years longer than those who do not exercise. Plus, there is substantially less disease among those who exercise regularly.

Professional societies:
2003- American Aging Association (AGE) Scientific Board Member
2003- Gerontological Society of America (GSA)
1997-2008 The American Physiological Society (APS)
1995-2008 Society for Free Radical Biology and Medicine (SFRBM)
1995-2008 International Society for Free Radical Research (ISFRBM) Editorial board: Journal of Experimental Gerontology
2005-current Journal of the American Aging Association
2004-2006 Editor Roles: Editor Journal of Experimental Gerontology
2008-current (Musculoskeletal Systems and Exercise, Section Editor) Guest Editor Antioxidant and Redox Signaling (2005-2006) (Aging)

Curriculum Vitae

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Publications

Xu, J., Jia, Z., Knutson, M.D., and Leeuwenburgh, C. 2012. Impaired iron status in aging research. International journal of molecular sciences 13:2368-2386.

Xu, J., Hwang, J.C., Lees, H.A., Wohlgemuth, S.E., Knutson, M.D., Judge, A.R., Dupont-Versteegden, E.E., Marzetti, E., and Leeuwenburgh, C. 2012. Long-term perturbation of muscle iron homeostasis following hindlimb suspension in old rats is associated with high levels of oxidative stress and impaired recovery from atrophy. Experimental gerontology 47:100-108.

Wang, J.H., Behrns, K.E., Leeuwenburgh, C., and Kim, J.S. 2012. Critical role of autophage in ischemia/reperfusion injury to aged livers. Autophagy 8:140-141.

Sibille, K.T., Langaee, T., Burkley, B., Gong, Y., Glover, T.L., King, C., Riley, J.L., 3rd, Leeuwenburgh, C., Staud, R., Bradley, L.A., et al. 2012. Chronic pain, perceived stress, and cellular aging: an exploratory study. Molecular pain 8:12.

Picca, A., Fracasso, F., Pesce, V., Cantatore, P., Joseph, A.M., Leeuwenburgh, C., Gadaleta, M.N., and Lezza, A.M. 2012. Age- and calorie restriction-related changes in rat brain mitochondrial DNA and TFAM binding. Age.

Muller-Delp, J.M., Gurovich, A.N., Christou, D.D., and Leeuwenburgh, C. 2012. Redox balance in the aging microcirculation: new friends, new foes, and new clinical directions. Microcirculation 19:19-28.

Marzetti, E., Lees, H.A., Manini, T.M., Buford, T.W., Aranda, J.M., Jr., Calvani, R., Capuani, G., Marsiske, M., Lott, D.J., Vandenborne, K., et al. 2012. Skeletal muscle apoptotic signaling predicts thigh muscle volume and gait speed in community-dwelling older persons: an exploratory study. PloS one 7:e32829.

Marzetti, E., Calvani, R., Bernabei, R., and Leeuwenburgh, C. 2012. Apoptosis in skeletal myocytes: a potential target for interventions against sarcopenia and physical frailty – a mini-review. Gerontology 58:99-106.

Joseph, A.M., Adhihetty, P.J., Buford, T.W., Wohlgemuth, S.E., Lees, H.A., Nguyen, L.M., Aranda, J.M., Sandesara, B.D., Pahor, M., Manini, T.M., et al. 2012. The impact of aging on mitochondrial function and biogenesis pathways in skeletal muscle of sedentary high- and low-functioning elderly individuals. Aging cell.

Dutta, D., Calvani, R., Bernabei, R., Leeuwenburgh, C., and Marzetti, E. 2012. Contribution of impaired mitochondrial autophagy to cardiac aging: mechanisms and therapeutic opportunities. Circulation research 110:1125-1138.

Chmielewski, T.L., Trumble, T.N., Joseph, A.M., Shuster, J., Indelicato, P.A., Moser, M.W., Cicuttini, F.M., and Leeuwenburgh, C. 2012. Urinary CTX-II concentrations are elevated and associated with knee pain and function in subjects with ACL reconstruction. Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society.

Carter, C.S., Marzetti, E., Leeuwenburgh, C., Manini, T., Foster, T.C., Groban, L., Scarpace, P.J., and Morgan, D. 2012. Usefulness of preclinical models for assessing the efficacy of late-life interventions for sarcopenia. The journals of gerontology. Series A, Biological sciences and medical sciences 67:17-27.

Buford, T.W., Lott, D.J., Marzetti, E., Wohlgemuth, S.E., Vandenborne, K., Pahor, M., Leeuwenburgh, C., and Manini, T.M. 2012. Age-related differences in lower extremity tissue compartments and associations with physical function in older adults. Experimental gerontology 47:38-44.

Aris, J.P., Fishwick, L.K., Marraffini, M.L., Seo, A.Y., Leeuwenburgh, C., and Dunn, W.A., Jr. 2012. Amino Acid Homeostasis and Chronological Longevity in Saccharomyces cerevisiae. Sub-cellular biochemistry 57:161-186.

Wohlgemuth, S.E., Lees, H.A., Marzetti, E., Manini, T.M., Aranda, J.M., Daniels, M.J., Pahor, M., Perri, M.G., Leeuwenburgh, C., and Anton, S.D. 2011. An exploratory analysis of the effects of a weight loss plus exercise program on cellular quality control mechanisms in older overweight women. Rejuvenation research 14:315-324.

Wang, J.H., Ahn, I.S., Fischer, T.D., Byeon, J.I., Dunn, W.A., Jr., Behrns, K.E., Leeuwenburgh, C., and Kim, J.S. 2011. Autophagy suppresses age-dependent ischemia and reperfusion injury in livers of mice. Gastroenterology 141:2188-2199 e2186.

Nocera, J., Buford, T.W., Manini, T.M., Naugle, K., Leeuwenburgh, C., Pahor, M., Perri, M.G., and Anton, S.D. 2011. The impact of behavioral intervention on obesity mediated declines in mobility function: implications for longevity. Journal of aging research 2011:392510.

Manini, T.M., Vincent, K.R., Leeuwenburgh, C., Lees, H.A., Kavazis, A.N., Borst, S.E., and Clark, B.C. 2011. Myogenic and proteolytic mRNA expression following blood flow restricted exercise. Acta physiologica 201:255-263.

Leeuwenburgh, C., Pamplona, R., and Sanz, A. 2011. Mitochondria and aging. Journal of aging research 2011:782946.

Kim, J.M., Heo, H.S., Choi, Y.J., Ye, B.H., Mi Ha, Y., Seo, A.Y., Yu, B.P., Leeuwenburgh, C., Chung, H.Y., and Carter, C.S. 2011. Inhibition of NF-kappaB-induced inflammatory responses by angiotensin II antagonists in aged rat kidney. Experimental gerontology 46:542-548.

Gesing, A., Masternak, M.M., Wang, F., Joseph, A.M., Leeuwenburgh, C., Westbrook, R., Lewinski, A., Karbownik-Lewinska, M., and Bartke, A. 2011. Expression of key regulators of mitochondrial biogenesis in growth hormone receptor knockout (GHRKO) mice is enhanced but is not further improved by other potential life-extending interventions. The journals of gerontology. Series A, Biological sciences and medical sciences 66:1062-1076.

Anton, S.D., Shuster, J., and Leeuwenburgh, C. 2011. Investigations of botanicals on food intake, satiety, weight loss and oxidative stress: study protocol of a double-blind, placebo-controlled, crossover study. Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine 9:1190-1198.

Anton, S.D., Manini, T.M., Milsom, V.A., Dubyak, P., Cesari, M., Cheng, J., Daniels, M.J., Marsiske, M., Pahor, M., Leeuwenburgh, C., et al. 2011. Effects of a weight loss plus exercise program on physical function in overweight, older women: a randomized controlled trial. Clinical interventions in aging 6:141-149.

Xu, J., Seo, A.Y., Vorobyeva, D.A., Carter, C.S., Anton, S.D., Lezza, A.M., and Leeuwenburgh, C. 2010. Beneficial effects of a Q-ter based nutritional mixture on functional performance, mitochondrial function, and oxidative stress in rats. PloS one 5:e10572.

Xu, J., Marzetti, E., Seo, A.Y., Kim, J.S., Prolla, T.A., and Leeuwenburgh, C. 2010. The emerging role of iron dyshomeostasis in the mitochondrial decay of aging. Mechanisms of ageing and development 131:487-493.

Wohlgemuth, S.E., Seo, A.Y., Marzetti, E., Lees, H.A., and Leeuwenburgh, C. 2010. Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise. Experimental gerontology 45:138-148.

Someya, S., Yu, W., Hallows, W.C., Xu, J., Vann, J.M., Leeuwenburgh, C., Tanokura, M., Denu, J.M., and Prolla, T.A. 2010. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 143:802-812.

Seo, A.Y., Joseph, A.M., Dutta, D., Hwang, J.C., Aris, J.P., and Leeuwenburgh, C. 2010. New insights into the role of mitochondria in aging: mitochondrial dynamics and more. Journal of cell science 123:2533-2542.

Predmore, B.L., Alendy, M.J., Ahmed, K.I., Leeuwenburgh, C., and Julian, D. 2010. The hydrogen sulfide signaling system: changes during aging and the benefits of caloric restriction. Age 32:467-481.

Opalach, K., Rangaraju, S., Madorsky, I., Leeuwenburgh, C., and Notterpek, L. 2010. Lifelong calorie restriction alleviates age-related oxidative damage in peripheral nerves. Rejuvenation research 13:65-74.

Marzetti, E., Privitera, G., Simili, V., Wohlgemuth, S.E., Aulisa, L., Pahor, M., and Leeuwenburgh, C. 2010. Multiple pathways to the same end: mechanisms of myonuclear apoptosis in sarcopenia of aging. TheScientificWorldJournal 10:340-349.

Marzetti, E., Hwang, J.C., Lees, H.A., Wohlgemuth, S.E., Dupont-Versteegden, E.E., Carter, C.S., Bernabei, R., and Leeuwenburgh, C. 2010. Mitochondrial death effectors: relevance to sarcopenia and disuse muscle atrophy. Biochimica et biophysica acta 1800:235-244.

Joyner-Matos, J., Predmore, B.L., Stein, J.R., Leeuwenburgh, C., and Julian, D. 2010. Hydrogen sulfide induces oxidative damage to RNA and DNA in a sulfide-tolerant marine invertebrate. Physiological and biochemical zoology : PBZ 83:356-365.

Hong, S.E., Heo, H.S., Kim, D.H., Kim, M.S., Kim, C.H., Lee, J., Yoo, M.A., Yu, B.P., Leeuwenburgh, C., and Chung, H.Y. 2010. Revealing system-level correlations between aging and calorie restriction using a mouse transcriptome. Age 32:15-30.

Hiona, A., Sanz, A., Kujoth, G.C., Pamplona, R., Seo, A.Y., Hofer, T., Someya, S., Miyakawa, T., Nakayama, C., Samhan-Arias, A.K., et al. 2010. Mitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator mice. PloS one 5:e11468.

Giovannini, S., Onder, G., Leeuwenburgh, C., Carter, C., Marzetti, E., Russo, A., Capoluongo, E., Pahor, M., Bernabei, R., and Landi, F. 2010. Myeloperoxidase levels and mortality in frail community-living elderly individuals. The journals of gerontology. Series A, Biological sciences and medical sciences 65:369-376.

Giovannini, S., Cesari, M., Marzetti, E., Leeuwenburgh, C., Maggio, M., and Pahor, M. 2010. Effects of ACE-inhibition on IGF-1 and IGFBP-3 concentrations in older adults with high cardiovascular risk profile. The journal of nutrition, health & aging 14:457-460.

Buford, T.W., Cooke, M.B., Manini, T.M., Leeuwenburgh, C., and Willoughby, D.S. 2010. Effects of age and sedentary lifestyle on skeletal muscle NF-kappaB signaling in men. The journals of gerontology. Series A, Biological sciences and medical sciences 65:532-537.

Buford, T.W., Anton, S.D., Judge, A.R., Marzetti, E., Wohlgemuth, S.E., Carter, C.S., Leeuwenburgh, C., Pahor, M., and Manini, T.M. 2010. Models of accelerated sarcopenia: critical pieces for solving the puzzle of age-related muscle atrophy. Ageing research reviews 9:369-383.

Baur, J.A., Chen, D., Chini, E.N., Chua, K., Cohen, H.Y., de Cabo, R., Deng, C., Dimmeler, S., Gius, D., Guarente, L.P., et al. 2010. Dietary restriction: standing up for sirtuins. Science 329:1012-1013; author reply 1013-1014.

Someya, S., Xu, J., Kondo, K., Ding, D., Salvi, R.J., Yamasoba, T., Rabinovitch, P.S., Weindruch, R., Leeuwenburgh, C., Tanokura, M., et al. 2009. Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis. Proceedings of the National Academy of Sciences of the United States of America 106:19432-19437.

Roark, A.M., Bjorndal, K.A., Bolten, A.B., and Leeuwenburgh, C. 2009. Biochemical indices as correlates of recent growth in juvenile green turtles (Chelonia mydas). Journal of experimental marine biology and ecology 376:59-67.

Rangaraju, S., Hankins, D., Madorsky, I., Madorsky, E., Lee, W.H., Carter, C.S., Leeuwenburgh, C., and Notterpek, L. 2009. Molecular architecture of myelinated peripheral nerves is supported by calorie restriction with aging. Aging cell 8:178-191.

Marzetti, E., Wohlgemuth, S.E., Anton, S.D., Bernabei, R., Carter, C.S., and Leeuwenburgh, C. 2009. Cellular mechanisms of cardioprotection by calorie restriction: state of the science and future perspectives. Clinics in geriatric medicine 25:715-732, ix.

Marzetti, E., Lees, H.A., Wohlgemuth, S.E., and Leeuwenburgh, C. 2009. Sarcopenia of aging: underlying cellular mechanisms and protection by calorie restriction. BioFactors 35:28-35.

Marzetti, E., Carter, C.S., Wohlgemuth, S.E., Lees, H.A., Giovannini, S., Anderson, B., Quinn, L.S., and Leeuwenburgh, C. 2009. Changes in IL-15 expression and death-receptor apoptotic signaling in rat gastrocnemius muscle with aging and life-long calorie restriction. Mechanisms of ageing and development 130:272-280.

Kim, J.Y., Kim, D.H., Choi, J., Park, J.K., Jeong, K.S., Leeuwenburgh, C., Yu, B.P., and Chung, H.Y. 2009. Changes in lipid distribution during aging and its modulation by calorie restriction. Age 31:127-142.

Hofer, T., Servais, S., Seo, A.Y., Marzetti, E., Hiona, A., Upadhyay, S.J., Wohlgemuth, S.E., and Leeuwenburgh, C. 2009. Bioenergetics and permeability transition pore opening in heart subsarcolemmal and interfibrillar mitochondria: effects of aging and lifelong calorie restriction. Mechanisms of ageing and development 130:297-307.

Cui, L., Hofer, T., Rani, A., Leeuwenburgh, C., and Foster, T.C. 2009. Comparison of lifelong and late life exercise on oxidative stress in the cerebellum. Neurobiology of aging 30:903-909.

Chung, H.Y., Cesari, M., Anton, S., Marzetti, E., Giovannini, S., Seo, A.Y., Carter, C., Yu, B.P., and Leeuwenburgh, C. 2009. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing research reviews 8:18-30.

Carter, C.S., Leeuwenburgh, C., Daniels, M., and Foster, T.C. 2009. Influence of calorie restriction on measures of age-related cognitive decline: role of increased physical activity. The journals of gerontology. Series A, Biological sciences and medical sciences 64:850-859.

Bailey, L.J., Cluett, T.J., Reyes, A., Prolla, T.A., Poulton, J., Leeuwenburgh, C., and Holt, I.J. 2009. Mice expressing an error-prone DNA polymerase in mitochondria display elevated replication pausing and chromosomal breakage at fragile sites of mitochondrial DNA. Nucleic acids research 37:2327-2335.

Xu, J., Knutson, M.D., Carter, C.S., and Leeuwenburgh, C. 2008. Iron accumulation with age, oxidative stress and functional decline. PloS one 3:e2865.

Strong, R., Miller, R.A., Astle, C.M., Floyd, R.A., Flurkey, K., Hensley, K.L., Javors, M.A., Leeuwenburgh, C., Nelson, J.F., Ongini, E., et al. 2008. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging cell 7:641-650.

Seo, A.Y., Xu, J., Servais, S., Hofer, T., Marzetti, E., Wohlgemuth, S.E., Knutson, M.D., Chung, H.Y., and Leeuwenburgh, C. 2008. Mitochondrial iron accumulation with age and functional consequences. Aging cell 7:706-716.

Raghavan, S., Kristinsson, H.G., and Leeuwenburgh, C. 2008. Radical scavenging and reducing ability of tilapia (Oreochromis niloticus) protein hydrolysates. Journal of agricultural and food chemistry 56:10359-10367.

Marzetti, E., Wohlgemuth, S.E., Lees, H.A., Chung, H.Y., Giovannini, S., and Leeuwenburgh, C. 2008. Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle. Mechanisms of ageing and development 129:542-549.

Marzetti, E., Lawler, J.M., Hiona, A., Manini, T., Seo, A.Y., and Leeuwenburgh, C. 2008. Modulation of age-induced apoptotic signaling and cellular remodeling by exercise and calorie restriction in skeletal muscle. Free radical biology & medicine 44:160-168.

Marzetti, E., Groban, L., Wohlgemuth, S.E., Lees, H.A., Lin, M., Jobe, H., Giovannini, S., Leeuwenburgh, C., and Carter, C.S. 2008. Effects of short-term GH supplementation and treadmill exercise training on physical performance and skeletal muscle apoptosis in old rats. American journal of physiology. Regulatory, integrative and comparative physiology 294:R558-567.

Lezza, A.M., Fallacara, F.P., Pesce, V., Leeuwenburgh, C., Cantatore, P., and Gadaleta, M.N. 2008. Localization of abasic sites and single-strand breaks in mitochondrial DNA from brain of aged rat, treated or not with caloric restriction diet. Neurochemical research 33:2609-2614.

Knutson, M.D., and Leeuwenburgh, C. 2008. Resveratrol and novel potent activators of SIRT1: effects on aging and age-related diseases. Nutrition reviews 66:591-596.

Kim, J.H., Kwak, H.B., Leeuwenburgh, C., and Lawler, J.M. 2008. Lifelong exercise and mild (8%) caloric restriction attenuate age-induced alterations in plantaris muscle morphology, oxidative stress and IGF-1 in the Fischer-344 rat. Experimental gerontology 43:317-329.

Hofer, T., Marzetti, E., Xu, J., Seo, A.Y., Gulec, S., Knutson, M.D., Leeuwenburgh, C., and Dupont-Versteegden, E.E. 2008. Increased iron content and RNA oxidative damage in skeletal muscle with aging and disuse atrophy. Experimental gerontology 43:563-570.

Hofer, T., Fontana, L., Anton, S.D., Weiss, E.P., Villareal, D., Malayappan, B., and Leeuwenburgh, C. 2008. Long-term effects of caloric restriction or exercise on DNA and RNA oxidation levels in white blood cells and urine in humans. Rejuvenation research 11:793-799.

Hiona, A., and Leeuwenburgh, C. 2008. The role of mitochondrial DNA mutations in aging and sarcopenia: implications for the mitochondrial vicious cycle theory of aging. Experimental gerontology 43:24-33.

Giovannini, S., Marzetti, E., Borst, S.E., and Leeuwenburgh, C. 2008. Modulation of GH/IGF-1 axis: potential strategies to counteract sarcopenia in older adults. Mechanisms of ageing and development 129:593-601.

Dirks Naylor, A.J., and Leeuwenburgh, C. 2008. Sarcopenia: the role of apoptosis and modulation by caloric restriction. Exercise and sport sciences reviews 36:19-24.

Chung, J.H., Seo, A.Y., Chung, S.W., Kim, M.K., Leeuwenburgh, C., Yu, B.P., and Chung, H.Y. 2008. Molecular mechanism of PPAR in the regulation of age-related inflammation. Ageing research reviews 7:126-136.

Barger, J.L., Kayo, T., Vann, J.M., Arias, E.B., Wang, J., Hacker, T.A., Wang, Y., Raederstorff, D., Morrow, J.D., Leeuwenburgh, C., et al. 2008. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PloS one 3:e2264.

Wohlgemuth, S.E., Julian, D., Akin, D.E., Fried, J., Toscano, K., Leeuwenburgh, C., and Dunn, W.A., Jr. 2007. Autophagy in the heart and liver during normal aging and calorie restriction. Rejuvenation research 10:281-292.

Sanz, A., Hiona, A., Kujoth, G.C., Seo, A.Y., Hofer, T., Kouwenhoven, E., Kalani, R., Prolla, T.A., Barja, G., and Leeuwenburgh, C. 2007. Evaluation of sex differences on mitochondrial bioenergetics and apoptosis in mice. Experimental gerontology 42:173-182.

Miller, R.A., Harrison, D.E., Astle, C.M., Floyd, R.A., Flurkey, K., Hensley, K.L., Javors, M.A., Leeuwenburgh, C., Nelson, J.F., Ongini, E., et al. 2007. An Aging Interventions Testing Program: study design and interim report. Aging cell 6:565-575.

Malayappan, B., Garrett, T.J., Segal, M., and Leeuwenburgh, C. 2007. Urinary analysis of 8-oxoguanine, 8-oxoguanosine, fapy-guanine and 8-oxo-2′-deoxyguanosine by high-performance liquid chromatography-electrospray tandem mass spectrometry as a measure of oxidative stress. Journal of chromatography. A 1167:54-62.

Judge, S., and Leeuwenburgh, C. 2007. Cardiac mitochondrial bioenergetics, oxidative stress, and aging. American journal of physiology. Cell physiology 292:C1983-1992.

Erdos, B., Broxson, C.S., Landa, T., Scarpace, P.J., Leeuwenburgh, C., Zhang, Y., and Tumer, N. 2007. Effects of life-long caloric restriction and voluntary exercise on age-related changes in levels of catecholamine biosynthetic enzymes and angiotensin II receptors in the rat adrenal medulla and hypothalamus. Experimental gerontology 42:745-752.

Carter, C.S., Hofer, T., Seo, A.Y., and Leeuwenburgh, C. 2007. Molecular mechanisms of life- and health-span extension: role of calorie restriction and exercise intervention. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme 32:954-966.

Borst, S.E., Conover, C.F., Carter, C.S., Gregory, C.M., Marzetti, E., Leeuwenburgh, C., Vandenborne, K., and Wronski, T.J. 2007. Anabolic effects of testosterone are preserved during inhibition of 5alpha-reductase. American journal of physiology. Endocrinology and metabolism 293:E507-514.

Seo, A.Y., Hofer, T., Sung, B., Judge, S., Chung, H.Y., and Leeuwenburgh, C. 2006. Hepatic oxidative stress during aging: effects of 8% long-term calorie restriction and lifelong exercise. Antioxidants & redox signaling 8:529-538.

Obisesan, T.O., Leeuwenburgh, C., Ferrell, R.E., Phares, D.A., McKenzie, J.A., Prior, S.J., and Hagberg, J.M. 2006. C-reactive protein genotype affects exercise training-induced changes in insulin sensitivity. Metabolism: clinical and experimental 55:453-460.

Marzetti, E., and Leeuwenburgh, C. 2006. Skeletal muscle apoptosis, sarcopenia and frailty at old age. Experimental gerontology 41:1234-1238.

Maraldi, C., Volpato, S., Kritchevsky, S.B., Cesari, M., Andresen, E., Leeuwenburgh, C., Harris, T.B., Newman, A.B., Kanaya, A., Johnson, K.C., et al. 2006. Impact of inflammation on the relationship among alcohol consumption, mortality, and cardiac events: the health, aging, and body composition study. Archives of internal medicine 166:1490-1497.

Leeuwenburgh, C., and Prolla, T.A. 2006. Genetics, redox signaling, oxidative stress, and apoptosis in mammalian aging. Antioxidants & redox signaling 8:503-505.

Kujoth, G.C., Leeuwenburgh, C., and Prolla, T.A. 2006. Mitochondrial DNA mutations and apoptosis in mammalian aging. Cancer research 66:7386-7389.

Kalani, R., Judge, S., Carter, C., Pahor, M., and Leeuwenburgh, C. 2006. Effects of caloric restriction and exercise on age-related, chronic inflammation assessed by C-reactive protein and interleukin-6. The journals of gerontology. Series A, Biological sciences and medical sciences 61:211-217.

Hofer, T., Seo, A.Y., Prudencio, M., and Leeuwenburgh, C. 2006. A method to determine RNA and DNA oxidation simultaneously by HPLC-ECD: greater RNA than DNA oxidation in rat liver after doxorubicin administration. Biological chemistry 387:103-111.

Hatao, H., Oh-ishi, S., Itoh, M., Leeuwenburgh, C., Ohno, H., Ookawara, T., Kishi, K., Yagyu, H., Nakamura, H., and Matsuoka, T. 2006. Effects of acute exercise on lung antioxidant enzymes in young and old rats. Mechanisms of ageing and development 127:384-390.

Dirks, A.J., and Leeuwenburgh, C. 2006. Caloric restriction in humans: potential pitfalls and health concerns. Mechanisms of ageing and development 127:1-7.

Dirks, A.J., and Leeuwenburgh, C. 2006. Tumor necrosis factor alpha signaling in skeletal muscle: effects of age and caloric restriction. The Journal of nutritional biochemistry 17:501-508.

Dirks, A.J., Hofer, T., Marzetti, E., Pahor, M., and Leeuwenburgh, C. 2006. Mitochondrial DNA mutations, energy metabolism and apoptosis in aging muscle. Ageing research reviews 5:179-195.

Deruisseau, K.C., Kavazis, A.N., Judge, S., Murlasits, Z., Deering, M.A., Quindry, J.C., Lee, Y., Falk, D.J., Leeuwenburgh, C., and Powers, S.K. 2006. Moderate caloric restriction increases diaphragmatic antioxidant enzyme mRNA, but not when combined with lifelong exercise. Antioxidants & redox signaling 8:539-547.

Cesari, M., Leeuwenburgh, C., Lauretani, F., Onder, G., Bandinelli, S., Maraldi, C., Guralnik, J.M., Pahor, M., and Ferrucci, L. 2006. Frailty syndrome and skeletal muscle: results from the Invecchiare in Chianti study. The American journal of clinical nutrition 83:1142-1148.

Cesari, M., Kritchevsky, S.B., Leeuwenburgh, C., and Pahor, M. 2006. Oxidative damage and platelet activation as new predictors of mobility disability and mortality in elders. Antioxidants & redox signaling 8:609-619.

Cassano, P., Sciancalepore, A.G., Lezza, A.M., Leeuwenburgh, C., Cantatore, P., and Gadaleta, M.N. 2006. Tissue-specific effect of age and caloric restriction diet on mitochondrial DNA content. Rejuvenation research 9:211-214.

Selsby, J.T., Judge, A.R., Yimlamai, T., Leeuwenburgh, C., and Dodd, S.L. 2005. Life long calorie restriction increases heat shock proteins and proteasome activity in soleus muscles of Fisher 344 rats. Experimental gerontology 40:37-42.

Selman, C., Phillips, T., Staib, J.L., Duncan, J.S., Leeuwenburgh, C., and Speakman, J.R. 2005. Energy expenditure of calorically restricted rats is higher than predicted from their altered body composition. Mechanisms of ageing and development 126:783-793.

Phillips, T., and Leeuwenburgh, C. 2005. Muscle fiber specific apoptosis and TNF-alpha signaling in sarcopenia are attenuated by life-long calorie restriction. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 19:668-670.

Leeuwenburgh, C., Gurley, C.M., Strotman, B.A., and Dupont-Versteegden, E.E. 2005. Age-related differences in apoptosis with disuse atrophy in soleus muscle. American journal of physiology. Regulatory, integrative and comparative physiology 288:R1288-1296.

Kujoth, G.C., Hiona, A., Pugh, T.D., Someya, S., Panzer, K., Wohlgemuth, S.E., Hofer, T., Seo, A.Y., Sullivan, R., Jobling, W.A., et al. 2005. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309:481-484.

Kakarla, P., Vadluri, G., Reddy, K.S., and Leeuwenburgh, C. 2005. Vulnerability of the mid aged rat myocardium to the age-induced oxidative stress: influence of exercise training on antioxidant defense system. Free radical research 39:1211-1217.

Judge, S., Jang, Y.M., Smith, A., Selman, C., Phillips, T., Speakman, J.R., Hagen, T., and Leeuwenburgh, C. 2005. Exercise by lifelong voluntary wheel running reduces subsarcolemmal and interfibrillar mitochondrial hydrogen peroxide production in the heart. American journal of physiology. Regulatory, integrative and comparative physiology 289:R1564-1572.

Judge, S., Jang, Y.M., Smith, A., Hagen, T., and Leeuwenburgh, C. 2005. Age-associated increases in oxidative stress and antioxidant enzyme activities in cardiac interfibrillar mitochondria: implications for the mitochondrial theory of aging. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 19:419-421.

Hiona, A., and Leeuwenburgh, C. 2005. WITHDRAWN: Life-long caloric restriction counteracts apoptotic effects of aging in the brain and bolsters the action of apoptosis inhibitors. Neurobiology of aging.

Dirks, A.J., and Leeuwenburgh, C. 2005. The role of apoptosis in age-related skeletal muscle atrophy. Sports medicine 35:473-483.

Phillips, T., and Leeuwenburgh, C. 2004. Lifelong aspirin supplementation as a means to extending life span. Rejuvenation research 7:243-251.

Obisesan, T.O., Leeuwenburgh, C., Phillips, T., Ferrell, R.E., Phares, D.A., Prior, S.J., and Hagberg, J.M. 2004. C-reactive protein genotypes affect baseline, but not exercise training-induced changes, in C-reactive protein levels. Arteriosclerosis, thrombosis, and vascular biology 24:1874-1879.

Julian, D., and Leeuwenburgh, C. 2004. Linkage between insulin and the free radical theory of aging. American journal of physiology. Regulatory, integrative and comparative physiology 286:R20-21.

Judge, S., Judge, A., Grune, T., and Leeuwenburgh, C. 2004. Short-term CR decreases cardiac mitochondrial oxidant production but increases carbonyl content. American journal of physiology. Regulatory, integrative and comparative physiology 286:R254-259.

Jang, Y.M., Kendaiah, S., Drew, B., Phillips, T., Selman, C., Julian, D., and Leeuwenburgh, C. 2004. Doxorubicin treatment in vivo activates caspase-12 mediated cardiac apoptosis in both male and female rats. FEBS letters 577:483-490.

Itoh, M., Oh-Ishi, S., Hatao, H., Leeuwenburgh, C., Selman, C., Ohno, H., Kizaki, T., Nakamura, H., and Matsuoka, T. 2004. Effects of dietary calcium restriction and acute exercise on the antioxidant enzyme system and oxidative stress in rat diaphragm. American journal of physiology. Regulatory, integrative and comparative physiology 287:R33-38.

Hiona, A., and Leeuwenburgh, C. 2004. Effects of age and caloric restriction on brain neuronal cell death/survival. Annals of the New York Academy of Sciences 1019:96-105.

Gredilla, R., Phaneuf, S., Selman, C., Kendaiah, S., Leeuwenburgh, C., and Barja, G. 2004. Short-term caloric restriction and sites of oxygen radical generation in kidney and skeletal muscle mitochondria. Annals of the New York Academy of Sciences 1019:333-342.

Drew, B., and Leeuwenburgh, C. 2004. Ageing and subcellular distribution of mitochondria: role of mitochondrial DNA deletions and energy production. Acta physiologica Scandinavica 182:333-341.

Dirks, A.J., and Leeuwenburgh, C. 2004. Aging and lifelong calorie restriction result in adaptations of skeletal muscle apoptosis repressor, apoptosis-inducing factor, X-linked inhibitor of apoptosis, caspase-3, and caspase-12. Free radical biology & medicine 36:27-39.

Cassano, P., Lezza, A.M., Leeuwenburgh, C., Cantatore, P., and Gadaleta, M.N. 2004. Measurement of the 4,834-bp mitochondrial DNA deletion level in aging rat liver and brain subjected or not to caloric restriction diet. Annals of the New York Academy of Sciences 1019:269-273.

Shelke, R.R., and Leeuwenburgh, C. 2003. Lifelong caloric restriction increases expression of apoptosis repressor with a caspase recruitment domain (ARC) in the brain. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17:494-496.

Selman, C., and Leeuwenburgh, C. 2003. The role of Id2 and apoptosis during skeletal muscle remodeling. American journal of physiology. Regulatory, integrative and comparative physiology 284:R538-539.

Selman, C., Kendaiah, S., Gredilla, R., and Leeuwenburgh, C. 2003. Increased hepatic apoptosis during short-term caloric restriction is not associated with an enhancement in caspase levels. Experimental gerontology 38:897-903.

Selman, C., Gredilla, R., Phaneuf, S., Kendaiah, S., Barja, G., and Leeuwenburgh, C. 2003. Short-term caloric restriction and regulatory proteins of apoptosis in heart, skeletal muscle and kidney of Fischer 344 rats. Biogerontology 4:141-147.

Phillips, T., Childs, A.C., Dreon, D.M., Phinney, S., and Leeuwenburgh, C. 2003. A dietary supplement attenuates IL-6 and CRP after eccentric exercise in untrained males. Medicine and science in sports and exercise 35:2032-2037.

Payne, A.M., Dodd, S.L., and Leeuwenburgh, C. 2003. Life-long calorie restriction in Fischer 344 rats attenuates age-related loss in skeletal muscle-specific force and reduces extracellular space. Journal of applied physiology 95:2554-2562.

Leeuwenburgh, C. 2003. Role of apoptosis in sarcopenia. The journals of gerontology. Series A, Biological sciences and medical sciences 58:999-1001.

Drew, B., Phaneuf, S., Dirks, A., Selman, C., Gredilla, R., Lezza, A., Barja, G., and Leeuwenburgh, C. 2003. Effects of aging and caloric restriction on mitochondrial energy production in gastrocnemius muscle and heart. American journal of physiology. Regulatory, integrative and comparative physiology 284:R474-480.

Drew, B., and Leeuwenburgh, C. 2003. Method for measuring ATP production in isolated mitochondria: ATP production in brain and liver mitochondria of Fischer-344 rats with age and caloric restriction. American journal of physiology. Regulatory, integrative and comparative physiology 285:R1259-1267.

Pollack, M., Phaneuf, S., Dirks, A., and Leeuwenburgh, C. 2002. The role of apoptosis in the normal aging brain, skeletal muscle, and heart. Annals of the New York Academy of Sciences 959:93-107.

Phaneuf, S., and Leeuwenburgh, C. 2002. Cytochrome c release from mitochondria in the aging heart: a possible mechanism for apoptosis with age. American journal of physiology. Regulatory, integrative and comparative physiology 282:R423-430.

Green, P.S., and Leeuwenburgh, C. 2002. Mitochondrial dysfunction is an early indicator of doxorubicin-induced apoptosis. Biochimica et biophysica acta 1588:94-101.

Drew, B., and Leeuwenburgh, C. 2002. Aging and the role of reactive nitrogen species. Annals of the New York Academy of Sciences 959:66-81.

Dirks, A., and Leeuwenburgh, C. 2002. Apoptosis in skeletal muscle with aging. American journal of physiology. Regulatory, integrative and comparative physiology 282:R519-527.

Childs, A.C., Phaneuf, S.L., Dirks, A.J., Phillips, T., and Leeuwenburgh, C. 2002. Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl-2:Bax ratio. Cancer research 62:4592-4598.

Pollack, M., and Leeuwenburgh, C. 2001. Apoptosis and aging: role of the mitochondria. The journals of gerontology. Series A, Biological sciences and medical sciences 56:B475-482.

Phaneuf, S., and Leeuwenburgh, C. 2001. Apoptosis and exercise. Medicine and science in sports and exercise 33:393-396.

Pennathur, S., Wagner, J.D., Leeuwenburgh, C., Litwak, K.N., and Heinecke, J.W. 2001. A hydroxyl radical-like species oxidizes cynomolgus monkey artery wall proteins in early diabetic vascular disease. The Journal of clinical investigation 107:853-860.

Leichtweis, S., Leeuwenburgh, C., Bejma, J., and Ji, L.L. 2001. Aged rat hearts are not more susceptible to ischemia-reperfusion injury in vivo: role of glutathione. Mechanisms of ageing and development 122:503-518.

Leeuwenburgh, C., and Heinecke, J.W. 2001. Oxidative stress and antioxidants in exercise. Current medicinal chemistry 8:829-838.

Childs, A., Jacobs, C., Kaminski, T., Halliwell, B., and Leeuwenburgh, C. 2001. Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise. Free radical biology & medicine 31:745-753.

Adams, S., Green, P., Claxton, R., Simcox, S., Williams, M.V., Walsh, K., and Leeuwenburgh, C. 2001. Reactive carbonyl formation by oxidative and non-oxidative pathways. Frontiers in bioscience : a journal and virtual library 6:A17-24.

Manary, M.J., Leeuwenburgh, C., and Heinecke, J.W. 2000. Increased oxidative stress in kwashiorkor. The Journal of pediatrics 137:421-424.

Powers, S.K., Ji, L.L., and Leeuwenburgh, C. 1999. Exercise training-induced alterations in skeletal muscle antioxidant capacity: a brief review. Medicine and science in sports and exercise 31:987-997.

Leeuwenburgh, C., Hansen, P.A., Holloszy, J.O., and Heinecke, J.W. 1999. Oxidized amino acids in the urine of aging rats: potential markers for assessing oxidative stress in vivo. The American journal of physiology 276:R128-135.

Leeuwenburgh, C., Hansen, P.A., Holloszy, J.O., and Heinecke, J.W. 1999. Hydroxyl radical generation during exercise increases mitochondrial protein oxidation and levels of urinary dityrosine. Free radical biology & medicine 27:186-192.

Heinecke, J.W., Hsu, F.F., Crowley, J.R., Hazen, S.L., Leeuwenburgh, C., Mueller, D.M., Rasmussen, J.E., and Turk, J. 1999. Detecting oxidative modification of biomolecules with isotope dilution mass spectrometry: sensitive and quantitative assays for oxidized amino acids in proteins and tissues. Methods in enzymology 300:124-144.

Gokce, N., Keaney, J.F., Jr., Frei, B., Holbrook, M., Olesiak, M., Zachariah, B.J., Leeuwenburgh, C., Heinecke, J.W., and Vita, J.A. 1999. Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 99:3234-3240.

Leeuwenburgh, C., and Ji, L.L. 1998. Glutathone and glutathione ethyl ester supplementation of mice alter glutathione homeostasis during exercise. The Journal of nutrition 128:2420-2426.

Leeuwenburgh, C., Hansen, P., Shaish, A., Holloszy, J.O., and Heinecke, J.W. 1998. Markers of protein oxidation by hydroxyl radical and reactive nitrogen species in tissues of aging rats. The American journal of physiology 274:R453-461.

Ji, L.L., Leeuwenburgh, C., Leichtweis, S., Gore, M., Fiebig, R., Hollander, J., and Bejma, J. 1998. Oxidative stress and aging. Role of exercise and its influences on antioxidant systems. Annals of the New York Academy of Sciences 854:102-117.

Gore, M., Fiebig, R., Hollander, J., Leeuwenburgh, C., Ohno, H., and Ji, L.L. 1998. Endurance training alters antioxidant enzyme gene expression in rat skeletal muscle. Canadian journal of physiology and pharmacology 76:1139-1145.

Crowley, J.R., Yarasheski, K., Leeuwenburgh, C., Turk, J., and Heinecke, J.W. 1998. Isotope dilution mass spectrometric quantification of 3-nitrotyrosine in proteins and tissues is facilitated by reduction to 3-aminotyrosine. Analytical biochemistry 259:127-135.

Tribble, D.L., Gong, E.L., Leeuwenburgh, C., Heinecke, J.W., Carlson, E.L., Verstuyft, J.G., and Epstein, C.J. 1997. Fatty streak formation in fat-fed mice expressing human copper-zinc superoxide dismutase. Arteriosclerosis, thrombosis, and vascular biology 17:1734-1740.

Leichtweis, S.B., Leeuwenburgh, C., Parmelee, D.J., Fiebig, R., and Ji, L.L. 1997. Rigorous swim training impairs mitochondrial function in post-ischaemic rat heart. Acta physiologica Scandinavica 160:139-148.

Leeuwenburgh, C., Wagner, P., Holloszy, J.O., Sohal, R.S., and Heinecke, J.W. 1997. Caloric restriction attenuates dityrosine cross-linking of cardiac and skeletal muscle proteins in aging mice. Archives of biochemistry and biophysics 346:74-80.

Leeuwenburgh, C., Rasmussen, J.E., Hsu, F.F., Mueller, D.M., Pennathur, S., and Heinecke, J.W. 1997. Mass spectrometric quantification of markers for protein oxidation by tyrosyl radical, copper, and hydroxyl radical in low density lipoprotein isolated from human atherosclerotic plaques. The Journal of biological chemistry 272:3520-3526.

Leeuwenburgh, C., Hollander, J., Leichtweis, S., Griffiths, M., Gore, M., and Ji, L.L. 1997. Adaptations of glutathione antioxidant system to endurance training are tissue and muscle fiber specific. The American journal of physiology 272:R363-369.

Leeuwenburgh, C., Hardy, M.M., Hazen, S.L., Wagner, P., Oh-ishi, S., Steinbrecher, U.P., and Heinecke, J.W. 1997. Reactive nitrogen intermediates promote low density lipoprotein oxidation in human atherosclerotic intima. The Journal of biological chemistry 272:1433-1436.

Leichtweis, S.B., Leeuwenburgh, C., Chandwaney, R., Parmelee, D.J., and Ji, L.L. 1996. Ischaemia-reperfusion induced alterations of mitochondrial function in hypertrophied rat heart. Acta physiologica Scandinavica 156:51-60.

Leeuwenburgh, C., Leichtweis, S., Hollander, J., Fiebig, R., Gore, M., and Ji, L.L. 1996. Effect of acute exercise on glutathione deficient heart. Molecular and cellular biochemistry 156:17-24.

Leeuwenburgh, C., and Ji, L.L. 1996. Alteration of glutathione and antioxidant status with exercise in unfed and refed rats. The Journal of nutrition 126:1833-1843.

Leeuwenburgh, C., and Ji, L.L. 1995. Glutathione depletion in rested and exercised mice: biochemical consequence and adaptation. Archives of biochemistry and biophysics 316:941-949.

Leeuwenburgh, C., Fiebig, R., Chandwaney, R., and Ji, L.L. 1994. Aging and exercise training in skeletal muscle: responses of glutathione and antioxidant enzyme systems. The American journal of physiology 267:R439-445.