ABSTRACT
Surprisingly little is known about the mechanisms of muscle atrophy with aging and disuse in human beings, in contrast to rodents, from which much has been extrapolated to explain the human condition. However, this extrapolation is likely unwarranted because the time course, extent of wasting, muscle fiber involvement and alterations of muscle protein turnover are all quite different in rodent and human muscle. Furthermore, there is little evidence that static indices of protein turnover represent dynamic changes and may be misleading. With disuse there are reductions in the rate of muscle protein synthesis (MPS) large enough to explain the atrophic loss of muscle protein without a concomitant increase in proteolysis. In aging, there is no evidence that there are marked alterations in basal muscle protein turnover in healthy individuals but instead the ability to maintain muscle after feeding is compromised. This anabolic resistance is evident with physical inactivity, which exacerbates the inability to maintain muscle mass with aging. The main conclusion of this review is that in uncomplicated, non-inflammatory disuse atrophy, the facilitative change causing loss of muscle mass is a depression of MPS, exacerbated by anabolic resistance during feeding, with possible adaptive depressions, rather than increases, of muscle proteolysis.
Subject(s)
Aging/metabolism , Muscle Proteins/metabolism , Muscular Atrophy/metabolism , Animals , Humans , Immobilization/physiology , Models, Animal , Muscle, Skeletal/metabolismABSTRACT
Inbred male and female Buffalo strain rats were started at 4, 8, 12, 24, or 52 weeks of age on 0.06% 3'-methyl-4-dimethylaminoazobenzene in a low-protein, choline-deficient diet. Eight-week-old males and females were the most susceptible to the development of chronic thyroiditis, but females were more susceptible than the males. Female rats of other ages developed a slightly higher incidence of thyroiditis than the male rats, the difference being most noticeable for rats 12 weeks old.
