Skeletal muscle plasticity after injury in old rats: effect of leucine supplementation

Abstract

There is a gradual loss of muscle mass and a remarkable deficit in the regenerative capacity of skeletal muscles during aging. Considering the ongoing increase of life expectancy and that the muscle mass integrity is crucial for the maintenance of quality of life, there is an increasing interest in the investigation of therapeutic strategies able to minimize the deleterious effects of aging upon the skeletal muscle. In this context, the study of possible therapeutic agents able to minimize the regenerative deficit of skeletal muscles from old rats is poorly understood. A good candidate could be the amino acid leucine, because it is an anabolic agent which could maximize the recovery of myofiber size during regeneration, leading to the improvement in muscle structure and function. Evidences show that supplementation with leucine activates factors involved in initiation of translation such as eIF-4E and the eIF-4G and the phosphorylation of p70S6K resulting in gain of muscle mass. In addition, studies have shown that the supplementation with leucine in animal models of muscle atrophy and caquexia results in increase of muscle mass through increase of protein synthesis, in which the PI3K/Akt/mTOR pathway is highly activated. Therefore, the role of nutritional supplementation with the leucine amino acid in muscle regeneration of young and old rats is still unknown. The objective of this project is to investigate the effect of leucine supplementation in skeletal muscle regeneration of cryolesioned young and old rats. The following aspects will be analyzed: macroscopic (muscle mass), histological (general morphology), immunohistochemical (detection of proliferating satellite cells and differentiating muscle cells), molecular (protein synthesis assay, activation profile of elements of PI3K/Akt/mTOR and ubiquitin-proteasome pathways) and functional (muscle contraction analysis) of regeneration of tibialis anterior muscles of young and old rats submitted to cryolesion (Please see more details in the session Material and Methods). (AU)