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 are studying members of the Calorie Restriction Society who have been practicing severe CR for many years. Our goals are to determine the health benefits of CR, and the extent to which CR slows aging in humans.

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

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

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.

Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell 7:681-687, 2008.

Holloszy JO. Regulation by exercise of skeletal muscle content of mitochondria and GLUT4. J. Physiol. Pharmacol. 59(Suppl 7):5-18, 2008

Holloszy JO. Skeletal muscle “mitochondrial deficiency” does not mediate insulin resistance. Am. J. Clin. Nutr. 89:463S-466S, 2009.

Hawley JA, Holloszy JO. Exercise: it’s the real thing! Nutr. Rev. 67:172-178, 2009.

Weiss EP, Shah K, Fontana L, Lambert CP, Holloszy JO, Villareal DT. Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone. Am. J. Clin. Nutr. 89:1459-1467, 2009

Kirwan JP, Solomon TP, Wojta DM, Slaten MA, Holloszy JO. Effects of 7 days of exercise training on insulin sensitivity and responsiveness in type 2 diabetes mellitus. Am. J. Physiol. Endocrinol. Metab. 297:E151-E156, 2009.

Han DH, Hancock CR, Jung SR, Holloszy JO. Is “fat-induced” muscle insulin resistance rapidly reversible? Am. J. Physiol. Endocrinol. Metab., 297:E236-E241, 2009.

Fontana L, Klein S, Holloszy JO. Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action, and adipokine production. Age 32:97-108, 2010.

Cangemi R, Friedmann, AJ, Holloszy JO, Fontana L. Long-term effects of calorie restriction on serum sex-hormone concentrations in men. Aging Cell 9:236-242, 2010.

Hancock CR, Han DH, Higashida K, Kim SH, Holloszy JO. Does calorie restriction induce mitochondrial biogenesis? A reevaluation. FASEB J. 2010 Nov 4. [Epub ahead of print]

Department of Medicine
Division of Geriatrics & Nutritional Sciences

John O. Holloszy, MD