To investigate the relationship of weight change to change in body composition in the Framingham Heart Study cohort, we entered into an agreement with the USDA Human Nutrition Research Center on Aging and researchers at Harvard School of Medicine and Boston University School of Medicine to obtain body composition measurements with dual energy x-ray absorptiometry (DEXA) for muscle, bone and body fat as well as to obtain reasons for weight change. Data collection of repeat body composition measurements is complete. NIA has had a major interest in frailty, both in terms of epidemiology and in terms of intervention studies. In addition, there is currently interest in trophic factors which may promote conservation of muscle in particular and aid in rehabilitation of frail older persons. This study allowed examination of body composition and mediators of weight loss in a major longitudinal study of now very old persons in which there has been assessment of weight, weight related risk factors, and many of the chronic diseases of importance in old age including heart disease, stroke, congestive heart failure, osteoarthritis, osteoporosis, pulmonary disease, and cancer, as well as indicators of inflammation. From this viewpoint, it would allow broadening of the perspective not only on frailty, but the interaction of frailty with comorbidity. Dr. Helaine Payette, working with Dr. Roubenoff, examined the relationship of the cytokine and other biologic data to risk of body composition change. With Dr. Roubenoff, we have conducted analysis of data with longitudinal outcomes proceeding, for example, cytokines and mortality. In addition, faculty at Boston University School of Medicine have used the cytokine measurements to predict onset of congestive heart failure. We continue to use these data and will look at this in relation to patterns of mortality.