Effects of short-term treadmill exercise training or growth hormone supplementation on diastolic function and exercise tolerance in old rats.

Whether the lusitropic potential of short-term exercise in aged rats is linked to an augmentation in the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and an alteration in the cardiac renin angiotensin system (RAS) is unknown. Old (28-month-old) male, Fischer 344xBrown Norway rats were randomized to 4 weeks of GH supplementation (300 microg subcutaneous, twice daily) or 4 weeks of treadmill running, or were used as sedentary controls. Six-month-old rats, sedentary or exercised, were used as young controls. Training improved exercise capacity in old animals. Exercise and GH attenuated age-related declines in myocardial relaxation despite an exercise-induced suppression of IGF-1. The regulatory protein, sarcoplasmic Ca2+ adenosine triphosphatase (SERCA2), increased with exercise but not GH. Among aged rats, the cardiac RAS was not altered by training or GH. Thus, the signaling pathway underlying the lusitropic benefit of short-term habitual exercise in the aged rat may be distinct from GH-mediated benefits and independent of the cardiac RAS.

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

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 mug 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.