Preventing the Loss of Muscle and Function in Hospitalized Older Adults

A majority of older adults experience repeated periods of physical inactivity during acute illnesses, injuries or after an operative procedure. Following discharge from the hospital, daily activities are adversely impacted. Infirmity follows repeated periods of inactivity (termed "catabolic hits") that can occur over an older adults' lifespan and lead to a downward spiral of potentially irrecoverable deficits in physical function resulting in increased health care costs, loss of independence, and premature death. The hallmark sign of short-term physical inactivity in older adults is the rapid deterioration of skeletal muscle mass and strength. Understandably, little attention is placed on physical function during these requisite periods of inactivity as the medical management and/or postoperative recuperation is the focus. However, the muscle deficits that follow as a result of acute hospitalization can have profound long-term consequences.

Muscle contraction and essential amino acids are powerful independent anabolic stimuli and fundamental to maintain skeletal muscle mass and strength. The primary mechanism of disuse atrophy during short-term bed rest in older adults is the reduced acute nutrient stimulation of muscle protein synthesis regulated by the mammalian target of rapamycin (mTOR) signaling pathway and amino acid transporter expression (i.e., LAT1). Intervening with essential amino acid supplements can maintain some muscle function in older adults during bed rest, but it does not preserve muscle mass. Neuromuscular electrical stimulation (NMES) as a muscle intervention is also feasible, but alone is not a panacea. NMES has recently been shown to acutely stimulate protein synthesis in ambulatory older adults with diabetes and attenuate some loss in muscle mass in critically ill patients. The investigator suggests that, together, daily NMES, and a high quality protein source of EAAs (PRO), can be a potent two-pronged approach to preserve the loss of muscle and strength in older adults confined to short-term bed rest. The goal is to test if the combination of NMES and PRO will maintain muscle mass, strength, nutrient-induced mTOR signaling and amino acid transporter expression in older adults during bed rest. The central hypothesis for this project which will support this next step is that a daily combination of NMES and PRO in older adults experiencing bed rest will preserve: 1) leg muscle mass and knee extensor strength and 2) muscle anabolic sensitivity in response to acute nutrient ingestion, as measured by mTOR signaling and LAT1 expression.

Inclusion criteria

Age between 60-85 yrs Ability to sign informed consent Montreal cognitive assessment (MOCA) exam score ≥26 Free-living, prior to admission

Exclusion criteria

• Cardiac abnormalities considered exclusionary by the study physician (e.g., CHF, CAD, right-to-left shunt)
• Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, diabetes)
• GFR <65 mL/min/1.73m2 or evidence of kidney disease or failure
• Vascular disease or risk factors of peripheral atherosclerosis. (e.g., uncontrolled hypertension, obesity, diabetes, hypercholesterolemia > 250 mg/dl, claudication or evidence of venous or arterial insufficiency upon palpitation of femoral, popliteal and pedal arteries)
• Risk of DVT including family history of thrombophilia, DVT, pulmonary emboli, myeloproliferative diseases including polycythemia (Hb>18 g/dL) or thrombocytosis (platelets>400x103/mL), and connective tissue diseases (positive lupus anticoagulant), hyperhomocysteinemia, deficiencies of factor V Leiden, proteins S and C, and antithrombin III
• Use of anticoagulant therapy (e.g., Coumadin, heparin)
• Elevated systolic pressure >150 or a diastolic blood pressure > 100
• Implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators)
• Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
• Currently on a weight-loss diet or body mass index > 30 kg/m2
• Inability to abstain from smoking for duration of study
• A history of > 20 pack per year smoking
• HIV or hepatitis B or C*
• Recent anabolic or corticosteroids use (within 3 months)
• Subjects with hemoglobin or hematocrit lower than accepted lab values
• Agitation/aggression disorder (by psychiatric history and exam)
• History of stroke with motor disability
• A recent history (<12 months) of GI bleed
• Depression [>5 on the 15 items Geriatric Depression Scale (GDS)]
• Alcohol or drug abuse
• Exercise training (>1 session of moderate to high intensity aerobic or resistance exercise/week)
• Liver disease (AST/ALT 2 times above the normal limit, hyperbilirubinemia)
• Respiratory disease (acute upper respiratory infection, history of chronic lung disease with resting oxygen saturation <97% on room air)
• Any other condition or event considered exclusionary by the PI and faculty physician