Preserving Muscle Mass and Function in Bedridden Older Adults

The loss of muscle mass and function in older adults during bed rest is facilitated by defects in the regulation of muscle protein metabolism, including an impaired ability to mount an anabolic response to a mixed nutrient meal. The investigators propose that low-intensity exercise and supplementing daily meals with leucine or whey will independently and synergistically reduce the deleterious effects of inactivity on skeletal muscle and facilitate recovery during rehabilitation. Metabolic measures will include: a) nutrient and exercise-specific markers of translation initiation; b) skeletal muscle protein synthesis; and c) a novel breath test of glucose tolerance. Morphologic and functional measures will include: a) muscle mass and body composition; b) muscle strength and function; and c) motor activation. The investigators will test the following hypotheses in older men and women (65-80 years) during 7 days of bed rest followed by 7 days of inpatient rehabilitation:

• Inactivity-induced metabolic dysregulation will blunt the anabolic response to meals, facilitating a loss of lean muscle mass, glucose tolerance and functional capacity that is partially restored during rehabilitation.
• Supplementing daily meals with leucine or whey will maintain nutrient-stimulated translation initiation and preserve the anabolic response to meal ingestion. This will partially preserve lean muscle mass and function during bed rest and facilitate the recovery of functional and metabolic capacity during rehabilitation.
• Daily low-intensity exercise will preserve motor unit activation, stimulate the exercise-regulated signaling pathway and normalize the anabolic response to meal ingestion. This will partially preserve glucose tolerance, lean muscle mass and function during bed rest and facilitate rehabilitation.

This translational project will provide mechanistic and practical insight into strategies to reduce the negative consequences of physical inactivity and promote rehabilitation in aging muscle. Our novel, minimally invasive and clinically interventions have direct application for older hospitalized patients at risk of accelerated muscle loss and diminished functional capacity.

Inclusion criteria

• Age between 60-80
• Ability to sign informed consent
• Ability to pass a mini-mental status exam
• Free-living, prior to admission

Exclusion criteria

• Subjects with cardiac abnormalities considered exclusionary by the study physicians
• Subjects with uncontrolled metabolic disease
• A glomerular filtration rate (GRF) <65 mL/min/1.73m2 or evidence of kidney disease or failure
• Subjects with 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.
• Any history of hypo- or hyper-coagulation disorders. (e.g., Coumadin use or history of deep vein thrombosis (DVT) or PE).
• Subjects with chronically elevated systolic pressure >170 or a diastolic blood pressure > 100.
• Subjects with implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators)
• Subjects with recently (6 months) treated cancer other than basal cell carcinoma
• Any subject currently on a weight-loss diet or a body mass index > 30 kg/m2.
• A history of > 20 pack per year smoking and/or inability to abstain from smoking for duration of study
• Any subject that is HIV-seropositive or has active hepatitis
• Recent anabolic or corticosteroids use (within 3 months).
• Subjects with hemoglobin or hematocrit lower than accepted lab values.
• Dementia, agitation/aggression disorder
• History of stroke with motor disability
• A recent history (<12 months) of GI bleed
• Any other condition or event considered exclusionary by the PI and faculty physician.