Preventing the Loss of Muscle and Function in Hospitalized Older Adults

Overview

One third of independent older adults over the age of 65y will be hospitalized for an acute medical illness, injury, or operative procedure. Unfortunately, 50% of these older adults will experience functional decline during their hospital stay from the amount of time they are physically inactive and in bed. Following discharge, the functional deficits can persist for months and in many instances never return to pre-hospitalization levels thus compounding morbidity, health care costs and dying. A classic consequence of short-term bed rest in older adults is the significant loss in skeletal muscle mass which underlies the accelerated leg strength deficits. The investigator has shown that an important mechanism of skeletal muscle loss is the inability of nutrients to stimulate a normal muscle protein synthesis response; a process highly regulated by the mammalian target of rapamycin signaling pathway (mTOR) and amino acid transporters. Day to day maintenance of force generating muscle tissue is dictated by anabolic stimulation from muscle contraction and essential amino acid ingestion. Therefore, anabolic interventions such as neuromuscular electrical stimulation (NMES) and high quality protein supplementation that contains a high proportion of essential amino acids (whey protein) may be promising approach to maintain leg muscle mass and strength in hospitalized older adults and prevent the long term consequences of repeated periods of short-term physical inactivity. The purpose of this study is to test in older adults if the combination of NMES and protein supplementation is capable of preserving muscle mass and strength and maintaining muscle nutrient anabolic sensitivity during bed rest. The investigators current hypotheses are that daily NMES and protein supplementation during 5-days of bed rest in older adults will: 1) preserve lower extremity muscle mass and strength and 2) maintain muscle nutrient anabolic sensitivity as measured by mTOR signaling and amino acid transporter expression. The long term goal is to utilize this inpatient preventative therapeutic approach in a clinical setting in which muscle mass and strength deficits are profound (e.g., intensive care patients).

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.