The reduction in the ability to produce muscular force for the maintenance of posture and locomotion is an age-related disorder of profound consequence and importance. In humans, the capacity to produce maximal force decreases 25% from the third to seventh decade of life. This functional deficit in aged humans is also observed in animals, and is associated with a decreased skeletal muscle myofibrillar protein content concomitant with a decreased number and size of muscle fibers. The long-term objectives are to understand the role of exercise training during aging, and the inherent capability of skeletal muscle from aged animals to adapt to a new stress, The specific aims are: a) to assess the mechanisms by which long-term exercise training affects skeletal muscle deficits in aging laboratory rats; and b) to determine if skeletal muscles from trained aged rats compared to sedentary aged rats have an enhanced capacity for adaptation to an increased workload induced by ablation of synergist muscles. Skeletal muscles will be studied from rats at 12, 18, 21 and 24 months of age; these ages are representative of important times in the development of age-associated muscle atrophy. An understanding of how deficits develop over time will facilitate understanding the mechanism(s) of such events. The proposed experiments will distinguish between inherent aging processes and changes that occur secondary to altered habitual exercise levels. This experimental objective is achieved by maintaining a constant training intensity and duration from 12 to 24 months, and by studying muscles which vary in habitual use patterns (diaphragm, soleus and plantaris muscles). Hypotheses will be tested with particular emphasis on protein synthesis and degradation and on innervation, as these mechanisms underlie aging and training effects. The parameters to be studied include structural (muscle composition, histochemistry, and innervation), functional (contractile properties), and biochemical (protein, metabolism and content, and innervation) variables. Our research objectives will be met by understanding several related variables. In particular, a mechanistic understanding of the biochemical and structural variables that dictate functional properties will be of high value.
