There is conclusive evidence that excess fat mass, independent of muscle mass, is a risk factor for physical function decline with aging. While, chronic resistance exercise improves functional ability in normal-weight older adults, obese individuals may not experience the same magnitude of benefit from a given exercise stimulus. Since specific inflammatory factors secreted by adipose tissue have direct effects on skeletal muscle morphologic and metabolic properties, it is likely that addition of caloric restriction resulting in loss of body fat to a resistance exercise intervention will be more efficacious for enhancing functional adaptations than exercise alone in obese elderly, a population at a particularly high risk for disability. This study is a randomized, clinical trial in 130 older (65-79 yrs), obese (BMI=30-34.9 kg/m2), sedentary women and men with low physical function designed to determine whether addition of caloric restriction (CR) to a standardized, progressive resistance training (RT) program enhances improvements in skeletal muscle and overall physical function. We will also examine the effects of the two interventions on in vitro characteristics of skeletal muscle and on systemic and abdominal adipose tissue levels of inflammation. Subjects will be randomized to 5 months of RT alone (RT) or RT with caloric restriction (RT+CR; -600 kcal/day deficit) designed to elicit considerable loss of body fat (<8.7 kg fat loss). The Specific Aims are to determine the effect of adding CR to RT on: 1) clinical measures of skeletal muscle function and overall physical function; 2) in vitro characteristics of skeletal muscle (single-fiber contractile force and power, intramyocellular lipid, and muscle gene and protein expression of interleukin-6 and tumor necrosis factor alpha); and 3) inflammatory activity of abdominal adipose tissue and circulating adipokines. Our primary hypothesis is: Compared to RT only, RT+CR will result in greater improvement in muscle function, assessed by knee extensor force per unit of muscle tissue (muscle quality) and leg press muscle power, and in overall physical function, assessed by Short Physical Performance Battery (SPPB) score. Confirmation of this hypothesis will provide persuasive evidence that addition of CR to a RT intervention in older, obese women and men may be a more effective treatment than RT alone for prevention or delay of disability. PUBLIC HEALTH RELEVANCE: This study will determine whether older, obese men and women who lose weight by dieting during a weight lifting program will experience greater improvements in muscle strength and physical function as a result of their exercise efforts. The results will also provide information on the effects of dieting during an exercise program on specific biological factors, including single muscle fiber strength, fat storage within muscle fibers, and inflammation in muscle and fat tissue.