PROJECT SUMMARY/ABSTRACT Declines in physical function with aging are an enormous clinical and public health problem that lead to increased disability, institutionalization, health care costs, lower quality of life and premature mortality. The burden of physical limitations and disability is higher in African compared with Caucasian individuals. Compounding the issue, older African Ancestry populations represent a rapidly growing segment of the population, especially outside the USA. For example, the number of individuals aged ≥60 in the Caribbean is expected to increase from 59 to 196 million by 2050. Black immigrants from the Caribbean differ from U.S. born African Americans and Black immigrants from Africa in rates of high blood pressure, diabetes, and obesity. These differences may be due in part to the greater Caucasian European Admixture (~25%) in African Americans compared with African Caribbeans (~6%). Yet, despite the clear scientific premise and need – there are no studies specifically designed to thoroughly examine physical function in African Caribbeans. Over the past 20 years, we have been studying a large cohort of African Caribbean men and women from Tobago in whom we have extensive measures of lifestyle habits, family and medical history, body composition, and biospecimens. We found that African Caribbeans have more lean mass (estimated muscle mass), but weaker muscle strength and higher levels of muscle fat than US adults. We have also discovered that changes in fat mass, but not lean mass, are important for future walking ability. However, many important gaps remain, and it is critical to expand measures of physical performance in this cohort. Therefore, we are proposing to address these gaps in the field by directly measuring skeletal muscle mass (d3 creatine dilution [D3Cr]) and performing deeper phenotyping of physical performance measures at each level in the disablement pathway to gain a comprehensive understanding of physical performance in this unique cohort of 1700 African Caribbeans. Aim 1 will use a wealth of existing data to test the hypothesis that both risk and protective factors more pronounced in African Caribbeans – specifically higher genetic African admixture, diabetes, and muscle fat infiltration - will be associated with changes in physical function with aging. Aims 2 and 3 will focus on new measures of body composition and physical performance that we are proposing to collect to test the hypotheses that: 1) lower muscle mass and greater muscle fat infiltration will be related to greater fatigability and worse physical performance, and 2) that poorer fat oxidation during walking will be associated with greater total fat and muscle fat, as well as greater fatigability and worse physical performance. Successful completion of these aims will provide the first direct assessment of skeletal muscle mass and comprehensive investigation of physical performance in African Caribbeans, a vastly under- studied, but rapidly growing population and lay the foundation for future investigations. These data can be harnessed in future efforts to improve, prevention, and treatment of age-related declines in physical performance.

PROJECT NARRATIVE: African Caribbeans have a high burden of diabetes, muscle fat infiltration and muscle weakness, which may lead to higher levels of age-related physical limitations and disability; however, there is currently no comprehensive information from individuals in this geographic region on muscle and physical performance. Therefore, this study seeks to directly measure skeletal muscle mass, and comprehensively phenotype physical performance in a large, established cohort of African Caribbean men and women living on the island of Tobago. This information can be used in future efforts to better prevent age-related declines in muscle and physical performance – an enormous public health issue – which will greatly enhance the quality of life of older adults in this region.