Even though skeletal muscle's response has been explored extensively following mechanical loading, it has been with respect to injurious loading, while more recently the effect of aging on muscle adaptation/maladaptation has been investigated implementing a novel non-injurious paradigm. Furthermore, the need for an integrated understanding of how the soft tissue response continuum is influenced is vital and must be approached by employing a systems biology approach. This is because the molecular, cellular, and functional mechanisms governing skeletal muscle adaptation/maladaptation following mechanical loading with aging are largely unknown. PURPOSE: The purpose of this study was to investigate if Akt serves as a molecular and cellular focal point for integrating both adaptive and/or maladaptive stimuli. Gene array, RT-PCR, and morphological localization, distribution, and quantification of Akt, and its influence on young and old skeletal muscle of rats following chronic high-intensity mechanical loading via stretch-shortening contractions (SSCs) was assessed. METHODS: Left dorsiflexor muscles of young (12 weeks, N=30) and old (30 months, N = 28) Fischer Brown Norway Hybrid rats, were loaded 3 times/week for 4.5-weeks using a protocol of 80 maximal SSCs per exposure in vivo. Tibialis anterior muscle was allocated for either gene expression or histology. RNA was isolated and prepared for gene array or RT-PCR. Additionally, transverse sections of the tibialis anterior muscle midbelly were cut and prepared for pan-Akt immunofluorescence and quantified using standard stereology and densitometry. RESULTS: Gene array data indicated that Akt 1 and 2 transcript levels were decreased in old rats compared with young rats. Follow-up analyses of transcript levels using RT-PCR confirmed these findings. Further, immunolabeling of tibialis anterior muscle tissue following the SSC loading period illustrated that the volume density of muscle fibers per section labeling positively for pan-Akt was decreased ~30% and ~35% in young and old rats, respectively. Moreover, the average percent area of pan-Akt+ labeling was decreased in both groups, but was decreased to a greater extent in old rats (~170%). CONCLUSIONS: Together, these findings suggest that Akt may act as a key modifier of incoming mechanical stimuli, which ultimately limits the adaptive potential of skeletal muscle with advanced age. Finally, these data provide only a basis for understanding this complex network of functionally relevant genes and proteins related to the adaptive/maladaptive process, which is currently limited.