PROJECT SUMMARY / ABSTRACT Deterioration of musculoskeletal tissues with age results in osteoarthritis, reduced mobility, and increased disability. Osteoarthritis (OA) frequently affects the knee and is the leading cause of disability worldwide. Poor muscle characteristics are associated with knee OA (KOA) and cross-sectional comparisons of healthy controls and KOA subjects show differences in muscle composition, quadriceps muscle strength and power. A few, small cross-sectional studies have also rigorously investigated muscle qualities associated with reduced mobility in older adults, independent of KOA, and reported reduced muscle mass, decreased ability to generate ATP, denervation, oxidative damage, and decreased autophagy. However, these clinical studies have been small, only cross-sectional, and often did not include individuals at risk for immobility or documented KOA. How these muscle qualities change with KOA is not known and represents a roadblock to understanding reduced mobility and increased disability in KOA. The NIA/NIH recently funded a Study of Muscle, Mobility and Aging (SOMMA), which just began enrolling 875 intermediate functioning, ethnically diverse women and men age >=70yrs. at two centers. The SOMMA study aims to 1) understand the contributions of skeletal muscle mass, energetics, and key properties of muscle tissue from biopsies to major immobility and disability; and 2) produce a unique bank of muscle tissue, blood, gene expression data, and clinical phenotyping to be used by the scientific community. We propose to obtain knee radiographs at the first SOMMA follow-up visit to understand the contributions of skeletal muscle mass and composition that leads to reduced mobility and disability in KOA subjects and if this differs from subjects without KOA. The Specific Aims are: Aim 1. Compare the baseline muscle properties (muscle strength, power, composition, ATPmax) in individuals with vs. without radiographic KOA, and with vs. without symptomatic KOA (radiographic KOA and pain). We will test the hypothesis that these muscle properties differ in subjects with radiographic KOA and symptomatic KOA compared to individuals without KOA (with and without pain). Aim 2. Determine whether radiographic KOA and symptomatic KOA are associated with functional outcomes (400m walking speed and Mobility Assessment Tool- short form, MAT-sf Disabiilty) independently of muscle characteristics (muscle strength, power and composition, ATPmax). We will test the hypothesis that persons with radiographic KOA and symptomatic KOA will have worse functional outcomes independent of muscle characteristics. Aim 3. Compare the association of muscle characteristics (composition, strength, power, ATPmax) with functional outcomes (400m walking speed and MAT-sf disability) in subjects with and without KOA, and with and without symptomatic KOA. We will test the hypothesis that the association of muscle characteristics with functional outcomes is different in ...