Faculty

John O. Holloszy, M.D.
Professor of Medicine
Director, Section of Applied Physiology

Research Interests

Dr. Holloszy’s current research runs along two lines:

Biochemical and Anatomical Adaptions to Exercise:
Our goal is to discover the mechanisms by which exercise induces an increase in muscle mitochondria. Another question of major interest that we plan to address is which of the perturbations in intracellular homeostasis during exercise serves as the signal that initiates induction of the adaptive increase in muscle mitochondria. Information obtained from this research may make it possible to mimic some of the beneficial effects of exercise through pharmacological or gene therapy intervention. Increasing muscle mitochondria using such approaches could compensate for mitochondrial mutations that contribute to muscle dysfunction as well as for pathophysiological effects of inactivity in patients with heart failure or advanced ISCHD.

Caloric Restriction and Aging in Humans:
Caloric restriction (CR) slows primary aging in various short-lived organisms, such as guppies, flies, mice and rats. It is not known if CR slows primary aging in humans. Secondary aging is due to disease processes and harmful lifestyle/environmental factors. Available evidence suggests that CR protects against some aspects of secondary aging in primates. In this context, we aim to determine the feasibility of achieving prolonged 20% restriction of energy intake or prolonged 20% increase of energy expenditure by exercise, in overweight 50-60 year old women and men and refine the techniques needed to achieve adherence to the CR and exercise protocols.

Contact Information

Washington University School of Medicine
660 S. Euclid Ave., Campus Box 8113
St. Louis, MO 63110-1093
Phone: (314) 362-3506
Fax: (314) 362-7657
E-mail: jhollosz@wustl.edu

Publications

Recent Articles in Peer Review Journals

Wright DC, Han DH, Garcia-Roves PM, Geiger PC, Jones TE, Holloszy JO. Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1alpha expression. J. Biol. Chem. 282:194-199, 2007.

Weiss EP, Racette SB, Villareal DT, Fontana L, Steger-May K, Schechtman KB, Klein S, AA Ehsani, Holloszy JO and the WUSM CALERIE Group. Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss. J. Appl. Physiol. 102:634-640, 2007.

Weiss EP, Holloszy JO. Improvements in body composition, glucose tolerance, and insulin action induced by increasing energy expenditure or decreasing energy intake. J. Nutr. 137:1087-1090, 2007.

Geiger PC, Hancock CR, Wright DC, Han DH, Holloszy JO. IL-6 increases muscle insulin sensitivity only at super-physiological levels. Am. J. Physiol. 292:E1842-E1846, 2007.

Garcia-Roves P, JM Huss, DH Han, CR Hancock, E Iglesias-Gutierrez, M Chen, JO Holloszy. Raising plasma fatty acid concentration induces increased biogenesis of mitochondria in skeletal muscle. PNAS 104:10709-10713, 2007.

Wright DC, Geiger PC, Han DH, Jones TE, Holloszy JO. Calcium induces increases in peroxisome proliferator-activated receptor gamma activated-1a and mitochondrial biogenesis by a pathway leading to p38 mitogen activated protein kinase activation. J.Biol.Chem. 282:18793-18799, 2007.

Fontana L, Villareal D, Weiss, EP, Racette SB, Steger-May K, Klein S, Holloszy JO and The WUSM CALERIE Group. Caloric restriction or exercise: Effects on coronary heart disease risk factors. A randomized controlled trial. Am. J. Physiol. 293:E197-E202, 2007.

Holloszy JO, Fontana L. Caloric restriction in humans. Experimental Gerontology 42:709-712, 2007.

Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term low-calorie low-protein vegan diet and endurance exercise are associated with low cardiometabolic risk. Rejuvenation Res. 10:225-234. 2007.

Arif H, Racette SB, Villareal DT, Holloszy JO and Weiss EP. Comparison of two methods for quantification of abdominal adipose tissue from magnetic resonance images. Obesity 15:2240-2244, 2007.

Wende AR, Schaeffer PJ, Parker GJ, Zechner C, Han DH, Chen MM, Hancock CR, Lehman JJ, Huss JM, McClain DA, Holloszy JO and Kelly DP. A role for the transcriptional coactivator PGC-1a in muscle refueling. J. Biol. Chem. 282:36642-36651, 2007

Riordan MM, Weiss EP, Meyer TE, Ehsani AA, Racette SB, Villareal DT, Fontana L, Holloszy JO, Kovacs SJ. The effects of caloric restriction- and exercise-induced weight loss on left ventricular diastolic function. Am. J. Physiol. 294:H1174-H1182, 2008.

Hancock CR, Han DH, Chen M, Terada S, Yasuda T, Wright DC, Holloszy JO. High fat diets cause insulin resistance despite an increase in muscle mitochondria. Proc. Natl. Acad. Sci. 105:7815-7820, 2008.

Racette SB, Weiss EP, Schechtman KB, Steger-May K, Villareal DT, Obert KA and Holloszy JO and The WUSM CALERIE team. Influence of weekend lifestyle patterns on body weight. Obesity, 2008 (In Press).

Department of Medicine
Division of Geriatrics & Nutritional Sciences

John O. Holloszy, MD