THE GENETIC CONTRIBUTION TO MUSCLE MASS AND PERFORMANCE IN AGING HUMANS

Wake Forest University Health Sciences, Winston-Salem NC

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Abstract

DESCRIPTION (provided by applicant): As people age, significant changes occur in body composition, including muscular alteration. These changes are the net result of a complex and poorly understood set of interdependent metabolic processes, which are also affected by environment and behavior. Total fat-free mass (FFM) correlates positively with total body mass (BM), generally resulting in increased FFM as individuals increase weight through middle age. Superimposed on this trend, however, are specific age-related declines in muscle mass and muscle performance (sarcopenia), which usually predominate during the sixth and subsequent decades of life. This age-related loss of muscle mass and performance is one of the major contributing factors to decline of function and disability in elderly populations. Although FFM is a significant determinant of overall physical function, intrinsic muscular strength and quality of retained muscle mass-both of which decline in the elderly--are also important. While the processes are universal, there is natural variation in the rates of sarcopenia and degree of muscular performance loss between individuals, and within different age groups. This application requests support for a cross-sectional pilot study to begin investigating the genetic components that underlie the changes in muscle mass and physical performance in an elderly population, defined here as individuals 60 yrs and older. 'The study will initially be restricted to a single site, with enrollment of sibling pairs from the locality of Wake Forest University Baptist Medical Center (WFUBMC). We will collect sibling pairs into our study, measure their muscle mass- and performancerelated phenotypes, and draw a blood sample to store for future genetic analysis. Recruitment of the sibling pairs will utilize several different recruitment approaches, including the existing VITAL (Volunteers in Touch with Aging and Life) database of 1,500+ older research subjects in the J. Paul Sticht Center at WFUBMC. This pilot study, and subsequent larger sample studies, will ultimately allow us to map genes and genetic variants that influence muscle mass and performance in aging humans, and will help explain the variation in the rates of decline between different elderly persons. This knowledge will help in the design of behavioral or pharmacological interventions targeted towards attenuating functional decline and increasing independence and quality of life in what will be a fastgrowing segment of the US population in the next 20-30 years.