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Am J Physiol Regul Integr Comp Physiol (November 14, 2007). doi:10.1152/ajpregu.00620.2007
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Submitted on August 27, 2007
Accepted on November 9, 2007

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

Emanuele Marzetti1*, Leanne Groban2, Stephanie Eva Wohlgemuth3, Hazel Lees4, Marina Lin2, Harrison Jobe5, Silvia Giovannini6, Christiaan Leeuwenburgh4, and Christy S Carter3

1 Aging and Geriatrics, University of Florida, Gainesville, Florida, United States; Department of Gerontology, Geriatrics and Physiatrics, Catholic University of the Sacred Heart, Rome, Italy
2 Winston-Salem, North Carolina, United States; Anesthesiology, Wake Forest University, Winston-Salem, North Carolina, United States
3 Aging and Geriatrics, University of Florida, Gainesville, Florida, United States
4 Gainesville, Florida, United States; Aging and Geriatrics, University of Florida, Gainesville, Florida, United States
5 Anesthesiology, Wake Forest University, Winston-Salem, North Carolina, United States
6 Gainesville, Florida, United States; Aging and Geriatrics, University of Florida, Gainesville, Florida, United States; Department of Gerontology, Geriatrics and Physiatrics, Catholic University of the Sacred Heart, Rome, Italy

* To whom correspondence should be addressed. E-mail: emarzetti{at}aging.ufl.edu.

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 months) male Fischer 344xBrown Norway rats were randomized to either 4 weeks of GH supplementation (300 µg subcutaneous, twice daily), 4 weeks 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, 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 (EDL) of old sedentary rats, which was attenuated by exercise. GH administration neither ameliorated physical performance nor attenuated apoptosis in EDL, and was associated with increased apoptosis in soleus (+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.







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