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.
Marzetti
Emanuele
E
Department of Aging and Geriatrics, Institute on Aging, Division of Biology of Aging, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA. emarzetti@aging.ufl.edu
Groban
Leanne
L
Wohlgemuth
Stephanie E
SE
Lees
Hazel A
HA
Lin
Marina
M
Jobe
Harrison
H
Giovannini
Silvia
S
Leeuwenburgh
Christiaan
C
Carter
Christy S
CS
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D013006:Growth Hormone / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D018657:Muscle Fibers, Slow-Twitch / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
C494831:Aifm1 protein, rat; D051033:Apoptosis Inducing Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D004706:Endodeoxyribonucleases; C052391:endonuclease G; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; D053148:Caspase 3; D053181:Caspase 8