The progressive wasting of skeletal muscle mass (sarcopenia) is a wide-spread, age-related pathological condition found in the modern elderly populations. The loss of muscle mass, paralleled by progressive muscular weakness, deteriorates the quality of living among the elderly, coincides with increased mortality and morbidity rates, and has an estimated healthcare cost of billions of dollars. Age-related muscle mass loss is reflected by microscopic changes in the muscle architecture, where loss of individual muscle fibers is one of the characteristic events. The nature and molecular mechanisms underlying age-related fiber loss (ARFL) and muscle wasting are apparently complex and currently not well understood. Thus, there is an urgent need for identification of a broad range of molecular targets that influence the rate of ARFL in aging muscles. This information will become critical in developing prophylactic and therapeutic approaches to curb age-related muscle wasting. My long-term goal is to identify genetic factors and molecular mechanisms that prolong healthy lifespan of muscles. The objectives here are to identify a range of muscle genes whose activity could be associated with increased resistance against ARFL. My central hypothesis is that greater muscle resistance to ARFL can be achieved cell-autonomously, through changes in muscle transcriptome, specifically by up- regulating expression of genes encoding structural muscle proteins. The expected outcome of this proposed project is an expansion in the list of genes and gene interactions essential to provide tolerance against age- related fiber degeneration and loss. These results will have a positive impact on human health as they will supply novel candidates for developing diagnostic and therapeutic approaches to detect and abrogate molecular processes leading to development of sarcopenia.
In this project, I will determine critical genetic factors and combination of factors that abrogate muscle fiber degeneration and loss, the phenomenon widely occurring in aging muscles and linked to sarcopenia. The proposed research is relevant to NIH's mission of enhancing human health as this knowledge will provide novel molecular targets for diagnostics and therapeutic treatment of sarcopenia.
