Project Summary/Abstract Obesity exacerbates age-related declines in physical function and is a strong determinant of mobility disability. Given that one-third of older adults are obese, identifying effective therapies that prevent obesity-related declines in physical function are urgently needed. The loss of lean mass with age contributes to age-related declines in physical function and current weight loss recommendations may further exacerbate this loss of lean mass. Although weight loss improves physical function while in the weight-reduced state, most individuals are not successful at long-term maintenance of weight loss. Furthermore, data from middle aged and older adults suggest that weight regain following weight loss is comprised of greater fat relative to lean mass. Consequently, weight loss and subsequent weight regain may lead to even less relative lean mass and worse physical function. The amount of protein consumed during weight loss may be a key determinant in preserving lean mass during weight loss and higher protein intake following weight loss may enhance weight loss maintenance by reducing overall weight regain, in part, by favoring regain of lean mass over fat. However, whether the potential benefit of lean mass retention and accretion with a higher protein diet during and subsequent to weight loss translates into greater improvements in physical function in obese older adults is unknown. Our primary goal is to determine whether a higher protein (1.2 g/kg body wt/d) / lower carbohydrate (CHO) diet during a 6-month weight loss intervention in obese older adults improves physical function compared with an isocaloric lower protein (current RDA of 0.8 g/kg body wt/d) / higher CHO diet and whether continuing a higher protein / lower CHO diet during the 12-month follow-up results in better maintenance of improved physical function. We propose to conduct an 18-month randomized trial in 225 obese (BMI 30-40 kg/m2), older (65-79 yrs) men and women at risk for disability (SPPB ?10) to determine the effects of a higher protein / lower CHO diet during a 6-month weight loss intervention followed by 12 months of follow-up on 1) physical function (assessed by the expanded Short Physical Performance Battery (expSPPB), muscle strength and power), and 2) weight maintenance and body composition (assessed by DXA and CT). We will also assess the effects of a higher protein / lower CHO diet on changes in bone mineral density and cardiometabolic risk factors. All participants will undergo a 6-month weight loss intervention followed by 12 months of follow-up with randomization to one of 3 groups: 1) lower protein / higher CHO diet for the 6-month weight loss and 12-month follow-up phases; 2) higher protein / lower CHO diet for the 6-month weight loss phase only; or 3) higher protein / lower CHO diet for the 6-month weight loss and 12-months follow-up phases. Determining whether a higher protein diet during and subsequent to weight loss maximizes potential benefits on physical function while minimizing potential adverse effects of weight loss (e.g., loss of lean and bone mass) may lead to more effective weight loss interventions for obese older adults.