The research in my laboratory over the past couple of years has been oriented in two areas of muscle research, although I am interested in many other peripheral areas of cell structure, function, and development. In spite of that, skeletal muscle remains the basis for my interests. Currently, the areas are:

1. Age-related changes in nucleo-cytoplasmic interactions in skeletal muscles

It is well known that skeletal muscles become smaller (atrophy) with aging, and this affects the quality of life of the elderly. We have been investigating the changes that occur in skeletal muscles or rat hindlimb after they have endured a period of microgravity during space flight. We have found that the muscles may atrophy by 30% within 10 days, and along with this atrophy, the nuclear population decreases. A skeletal muscle fiber is a multi-nucleated cell, and our results, along with others, have suggested that each nucleus controls a specific area of the muscle fiber (nuclear domain). Our results indicate that this domain is tightly regulated, so as the muscle fibers atrophy (resulting in less area per nucleus), the nuclei degenerate to maintain the same amount of cytoplasm they control. Other studies show that as the muscles enlarge during normal growth, muscle nuclei are added, indicating that regulation of nuclear domain size occurs in the other direction also. Our current studies are aimed at determining whether this tight control over nuclear domain remains in the elderly. We have strength-trained young versus elderly men and have been comparing the nuclear domain sizes as the muscle fibers hypertrophy (enlarge) with the training. It is possible that one of the factors that leads to aging atrophy of skeletal muscle is this loss of regulation of muscle nuclei.

2. Mechanisms of exercise- or activity-induced muscle damage and repair

Muscles get larger with strength training, and decrease in size with inactivity. Many factors may be interacting to cause these changes in fiber size, and we are exploring some of these. When a fiber increases in size, nuclei are added, but muscle nuclei are post-mitotic. This means that they do not undergo mitosis. The way that nuclei are added is by activation of closely associated cells called satellite cells that lie closely adjacent to each muscle fiber. When muscle fibers need more nuclei to grow or repair itself, the satellite cells undergo mitosis, and one of the daughter nuclei becomes incorporated into the muscle fiber as a new muscle nucleus. We are using monoclonal antibodies to determine whether these satellite cells are change in abundance with aging, and when these become activated. Other cells, macrophages, are also involved in the muscle repair process, and we are beginning to investigate what changes occur in these cells during muscle damage or repair.