Paddon-Jones, Douglas J2016-05-052016-05-052013-08August 201http://hdl.handle.net/2152.3/666Aging is associated with a slow, progressive loss of muscle mass and strength. Mechanical unloading, such as that commonly experienced during hospitalization or spaceflight, results in a rapid loss of muscle mass and strength, particularly in older adults. Exercise, a potent countermeasure to such losses, is often impractical in acutely ill patients. The essential amino acid leucine has been shown to acutely stimulate muscle protein synthesis (MPS), a decrease in which mechanistically drives inactivity-induced losses in muscle. This study evaluated the effects of leucine supplementation (0.06 g • kg • meal-1; LEU) with each of three daily meals in middle-aged adults, a largely unstudied age group, during 14 d bed rest (BR) and subsequent 7 d rehabilitation. Primary findings were: 1) leucine attenuated the loss of whole body lean mass during the first 7 d of BR compared to control subjects (LEU: -0.6±0.2 kg vs. CON: -1.1±0.2 kg, p<0.05) and reduced or prevented decrements in knee extensor strength (LEU: -8±3% vs. CON: -15±3%, p<0.05), ankle extensor strength (LEU: -13±5% vs. CON: -20±5%, p<0.05), and knee extensor endurance (LEU: -2±4% vs. CON: -14±3%, p<0.05) during 14 d BR; 2) LEU maintained both post-absorptive and post-prandial MPS during BR; in contrast, BR decreased post-absorptive MPS (pre-BR: 0.061% • h-1 vs. post-BR: 0.043% • h-1, p<0.05); 3) insulin area under the curve during an oral glucose tolerance test was unchanged in LEU after BR (21±8%) but elevated in CON (52±23%, p<0.05) and whole body insulin sensitivity in LEU was significantly increased above pre-BR values after 7 d rehabilitation (17±10% vs. CON: -9±9%, p<0.05). Leucine is an inexpensive, low volume supplement that can be easily incorporated into the daily meals of middle-aged adults to maintain muscle protein synthesis and protect muscle mass, strength, and insulin sensitivity during periods of physical inactivity characteristic of hospitalized acute illness and spaceflight.application/pdfBed restatrophymuscle metabolismprotein synthesismuscle massmuscle strengthinsulin sensitivityleucineessential amino acidnutritionagingmiddle-agedstable isotope tracerFSRmTORspaceflightThesis2016-05-05