Impaired Regulation of Muscle size with Aging

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Mechanisms controlling muscle size are poorly understood and it is unknown whether the same mechanisms are involved in muscles from young and old animals. Therefore, the goal of this study is to gain insight into mechanisms controlling muscle size and to determine whether these mechanisms are similar between young and old. The following hypothesis will be addressed: aging is associated with an impaired ability to maintain or restore muscles size in the face of an atrophy-inducing event. Three specific aims will be executed to address the hypothesis. In Specific Aim 1 the differences between young, adult and old rat muscles will be investigated in response to an atrophy-inducing event (hind limb suspension), to an atrophy preventing intervention (intermittent reloading during hind limb suspension) and a muscle mass restoring intervention (reloading after hind limb suspension)> It will be determine whether muscles from older rats react to the atrophy inducing events the same as muscles from young rats and whether the muscles from old rats can be restored in size as muscles from young rats are. In Specific Aim 2 different mechanisms known to influence muscle size in young animals are being investigated to determine whether these mechanisms are also involved to the same extent in older muscle. The role that satellite cells play and the involvement of apoptosis will be investigated in muscles from young, adult and old rats undergoing the above mentioned experimental paradigms. In Specific Aim 2 we will determine differences in gene expression in the muscles, undergoing the different experimental manipulations and compare changes in gene expression between young, adult and old muscles. We will look at a number of genes known to play a role in skeletal muscle atrophy and hypertrophy, but we will also use cDNA micro array technology to scan large numbers of genes that are not known yet to be involved in the regulation of muscle size. Results from these studies will indicate whether muscles from older animals restore or maintain muscle mass to the same extent as young animals and if underlying mechanisms are different in old compared to young muscles. Also, potential regulatory pathways and molecules involved in control of muscle size will be determined.