Chronic Muscle Disuse in the Elderly

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.

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.