Aging differences in mechanisms of human skeletal muscle hypertrophy

Sarcopenia, the age-associated loss of muscle mass, affects all individuals to varying degrees as years advance, and leads to decreases in strength, power and agility that contribute to increased frailty, the risk for falls and fractures, and morbidity. Of all the interventions tested, progressive resistance training has proven to be the most effective for increasing muscle mass, strength, and power, and enhancing functional parameters that are important for completion of tasks common in daily life.;The genetic and molecular mechanisms utilized by skeletal muscle to hypertrophy and/or atrophy are not well defined, and better understanding of these processes is required to develop more efficacious interventions aimed at decreasing/reversing the effects of sarcopenia. We examined the effects of progressive resistance training via percutaneous vastus lateralis biopsies on young (20-35 years) and older (60-75 years) men and women, and measured responses to training 24 hours after initial acute (1 full training sequence) and final training bouts of a 16 week program compared to a pretraining baseline.;We examined skeletal muscle cell cross sectional area and myosin heavy chain (MHC) expression to elucidate any differences in myofiber size and type distribution of MHC I, IIa and IIx among our subject groups. This study also included mRNA and protein examination of the myogenic regulatory factors (MRFs). A blunted hypertrophic response was measured in older adults, particularly in older men, while young men possessed the greatest magnitude of growth. No coordination between MRF transcript and protein was found, however, myf-6 protein upregulation was measured in men and may be important for myofiber growth.;Expression of select Dystrophin-Associated Protein Complex (DAPC) components was measured in young and older men, and reflects responsiveness in this scaffold to resistance training, primarily in young. Phosphorylated serine 1417 on nNOS and Mitogen-Activated Protein Kinase (MAPK) signaling proteins were also measured as indicators of activation (nNOS), proliferation/differentiation (Extracellular signal-Regulated Kinases (ERK1/2)) and cell stress/damage (p38) response. The measured alterations in phosphorylation states of nNOS serine 1417 and p38 in older men may indicate elevated cell stress/damage associated with training.