The present study examined the responses of apoptosis and apoptotic regulatory factors to muscle hypertrophy induced by stretch overload in quail slow-tonic muscles. The wing of young and aged Japanese quails from one side was loaded by attaching a tube weight corresponding to 12% of the bird's bodyweight for 7 or 21 days. Muscle from the contralateral side served as the intra-animal control. Relative to the intra-animal contralateral control side, the muscle wet weight increased by 96% in young birds whereas the muscle weight gain in aged birds was not significant following 7 days of loading. After 21 days of loading, muscle weight significantly increased by 179% and 102% in young and aged birds, respectively. HSP72 and HSP27 protein content in the loaded side was higher than the control side exclusively in young birds following 7 days of loading. Compared to the contralateral control muscle, the extent of apoptotic DNA fragmentation and the total cytosolic AIF protein content were reduced in all loaded muscles except for the 7 day loaded muscles from the aged birds. Bax protein content was diminished in the loaded muscle relative to the control side from all groups whereas Bcl-2 protein content was reduced in the young and aged muscles after 21 days of loading. The total cytosolic cytochrome c protein content was decreased and the XIAP protein content was elevated in 7 and 21 day-loaded muscles relative to the intra-animal control muscle from young birds. Furthermore, following 7 days of loading the muscles of aged birds, H₂O₂ content and the total cytosolic protein content of Smac/DIABLO were elevated when compared to the intra-animal control side. These data suggest that stretch overload-induced muscle hypertrophy is associated with changes of apoptosis in slow-tonic skeletal muscle. Moreover, discrepant apoptotic responses to muscle overload in young and aged muscles may in part account for the age-related diminishment of the capability for muscle hypertrophy.