Rodents

The effects of aging on muscle have been studied in both rats and mice. These animals offer the benefits of being small and easy to maintain in a laboratory environment, being familiar to many in the scientific community, having a growing number of identified genetic mutations, and having easily implemented transgenic technology.

Age-related muscle changes Both rats and mice show a decline in muscle mass during aging (Cartee, 1995). In rats this decline in muscle mass is due to both declines in muscle fiber number and fiber cross-sectional area. The declines in fiber number are less pronounced, but the declines in fiber cross-sectional areas are comparable to those seen in humans (Cartee, 1995). As seen in humans, the decline in fiber cross-sectional area is due predominantly to atrophy of type II muscle fibers. Interestingly, several muscles in the rat do not experience declines in muscle mass: the adductor longus, epitrochlearis, and flexor digitorum longus. Both epitro-chlearis and flexor digitorum longus have a comparable number of type II fibers compared to the gastrocnemius muscle, roughly 75%, that undergoes significant atrophy during aging. The reason for these differential susceptibilities to the effects of age on muscle is not known, but provides the advantage of having internal aged controls that can be used in studies. Mice also show declines in muscle mass, but this is due more to declines in cross-sectional area than declines in fiber number. However, the relative contributions of type I and type II fiber atrophy have not been well studied (Cartee, 1995).

Viral/transfection of muscles One approach to test the function of genes or mark specific cells for later histological study is to use trans-fection of foreign DNA transgenes. The transgene can consist of either specific genes of interest or marker genes like E. coli beta-galactosidase or GFP (green fluorescent protein) that can be easily detected on tissue sections. Transgenes are assembled in bacterial plasmids using standard recombinant DNA techniques, and the transgene consists of a promoter to direct expression in the muscle cell and a poly-adenylation sequence flanking the gene of interest or marker gene (see Figure 81.3).

Promoters can consist of muscle-specific promoters, such as the muscle creatinine kinase promoter; or strong viral promoters, such as the cytomegalovirus (CMV)

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