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Akt serves as a signaling pathway integrator for adaptation/maladaptation in aging muscle following mechanical loading.

Authors
Baker-BA; Ensey-J; Cutlip-RG
Source
Med Sci Sports Exerc 2010 Oct; 42(10)(Suppl 2):7-8
NIOSHTIC No.
20044019
Abstract
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.
Keywords
Musculoskeletal-system; Muscles; Age-factors; Biological-effects; Biological-factors; Biological-function; Animals; Laboratory-animals; Cellular-function; Cell-function; Genes
CODEN
MSPEDA
Publication Date
20101001
Document Type
Abstract
Email Address
bwb3@cdc.gov
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Issue of Publication
10
ISSN
0195-9131
NIOSH Division
HELD
Source Name
Medicine and Science in Sports and Exercise
State
WV
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