Chronic Muscle Disuse in the Elderly

The purpose of this study is to define the effects of chronic disuse on skeletal muscle structure and function in elderly individuals at the cellular and molecular level by examining elderly characterized by chronic muscle disuse (patients with knee osteoarthritis) and healthy elderly no evidence of knee osteoarthritis and normal physical activity levels.

Skeletal muscle disuse is an important contributing factor to physical disability. Disuse is more frequent in the elderly and they are more susceptible to its debilitating effects because of their diminished physiological reserve. Despite these facts, the mechanisms whereby disuse promotes skeletal muscle contractile dysfunction in this population remain largely undetermined. Therefore, the investigators will systematically test for modifications of single skeletal muscle fiber structure and function that underlie contractile dysfunction. Elderly individuals characterized by chronic muscle disuse (patients with knee osteoarthritis) will be compared to carefully-matched controls with no clinical evidence of knee osteoarthritis and normal activity levels. Thereafter, elderly with chronic disuse will undergo an exercise intervention to remediate muscle disuse. The investigators hypothesize that muscle disuse impairs contractile function, in part, through alterations in myosin kinetics, myofilament protein content and the mechanical properties of the myofilament lattice and that exercise rehabilitation will counteract these deficits. The investigators will specifically examine the effect of disuse on mechanical, kinetic and structural properties and molecular composition of single muscle fibers in cases and controls, as well as determine how increasing muscle use in elderly with chronic disuse via exercise training affects muscle fiber mechanical, kinetic and structural properties and molecular composition. These translational studies will provide the first comprehensive evaluation of the cellular and molecular mechanisms through which muscle disuse alters skeletal muscle structure and contractile function in elderly humans. This knowledge can assist in the development and refinement of preventative and corrective therapies for disability by tailoring these approaches to address specific molecular defects.

Exercise is being used as an experimental tool to determine if remediation of muscle disuse counteracts cellular/molecular defects in muscle structure/function.

KNEE OSTEOARTHRITIS PATIENTS Inclusion Criteria: 60-80 yrs of age physician-diagnosed, symptomatic knee osteoarthritis ambulatory and able to perform lower extremity resistance exercise Exclusion Criteria: rheumatoid arthritis or other autoimmune disease chronic heart, lung, kidney or liver disease or hypertension diabetes history of stroke other neurological or musculoskeletal disease HEALTHY CONTROLS Criteria are identical to those for knee osteoarthritis patients above, but controls will have no clinical or radiographic evidence of osteoarthritis and will have normal activity physical activity levels.

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