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Am J Physiol Regul Integr Comp Physiol 294: R558-R567, 2008. First published November 14, 2007; doi:10.1152/ajpregu.00620.2007
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ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY

Effects of short-term GH supplementation and treadmill exercise training on physical performance and skeletal muscle apoptosis in old rats

Emanuele Marzetti,1,2,* Leanne Groban,3,* Stephanie E. Wohlgemuth,1 Hazel A. Lees,1 Marina Lin,3 Harrison Jobe,3 Silvia Giovannini,1,2 Christiaan Leeuwenburgh,1 and Christy S. Carter1,4

1Department of Aging and Geriatrics, Institute on Aging, Division of Biology of Aging, University of Florida, Gainesville, Florida; 2Department of Gerontology, Geriatrics and Physiatrics, Catholic University of the Sacred Heart, Rome, Italy; 3Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; and 4Geriatric Research, Education, and Clinical Center, Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida

Submitted 27 August 2007 ; accepted in final form 9 November 2007

Growth hormone (GH) supplementation at old age has been shown to improve body composition, although its effect on muscle performance is still debated. On the other hand, resistance training increases muscle mass and strength even when initiated at advanced age. In the present study, we investigated the effects of short-term GH supplementation and exercise training on physical performance and skeletal muscle apoptosis in aged rats. Old (28 mo) male Fischer 344 x Brown Norway rats were randomized to 4 wk of GH supplementation (300 µg subcutaneous, twice daily) or 4 wk of treadmill running or used as sedentary controls. Eight-month-old rats, sedentary or exercised, were used as young controls. Exercise training improved exercise capacity and muscle strength in old animals. In soleus muscle, age and exercise were not associated with significant changes in the extent of apoptosis. However, we detected an age-related increase of cleaved caspase-8 (+98%), cleaved caspase-3 (+136%), and apoptotic DNA fragmentation (+203%) in the extensor digitorum longus muscle of old sedentary rats, which was attenuated by exercise. GH administration neither ameliorated physical performance nor attenuated apoptosis in extensor digitorum longus and was associated with increased apoptosis in soleus muscle (+206% vs. old controls). Our findings indicate that a short-term program of exercise training started at advanced age reverses age-related skeletal muscle apoptosis and represents an effective strategy to improve physical performance. In contrast, short-term administration of GH late in life does not provide any protection against functional decline or muscle aging and may even accelerate apoptosis in slow-twitch muscles, such as the soleus.

aging; sarcopenia; growth hormone; muscle quality; tumor necrosis factor-{alpha}



Addresses for reprint requests and other correspondence: E. Marzetti, Dept. of Aging and Geriatrics, Institute on Aging, Division of Biology of Aging, Univ. of Florida, 1600 SW Archer Road, Rm. P1-09, PO Box 100143, Gainesville, FL 32610 (e-mail: emarzetti{at}aging.ufl.edu); C. S. Carter, Department of Aging and Geriatrics, Institute on Aging, University of Florida, 1329 SW 16th Street, Room 5274, PO Box 100143, Gainesville, FL 32610-0143 (e-mail: ccarter{at}aging.ufl.edu)







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