Single Muscle Fiber Myosin-actin Interactions Slow More With Fatigue In Older Compared With Younger Muscle

PURPOSE: Older adults experience greater fatigue-related decrements in skeletal muscle power production compared with young adults. This study examined whether these age-related differences arise from altered single fiber contractile responses to fatiguing conditions (increased hydrogen ion (reduced pH) and inorganic phosphate (Pi) concentrations). METHODS: Single skinned fibers from the vastus lateralis muscle of 12 adults (6 young, 30-40 years; 6 older, 65-80 years) were tested under maximal calcium-activated control (pH = 7, Pi = 5 mM) and fatigue (pH = 6.2, Pi = 30 mM) conditions at 25 °C. RESULTS: Specific tension (maximal force/cross-sectional area) decreased with fatigue in both slow-contracting myosin heavy chain (MHC) I (24% + 0.80 younger, 26% + 0.99 older, p > 0.05) and fast-contracting MHC II (33% + 1.33 younger, 37% + 1.28 older, p > 0.05) fibers, with no effect of age (p > 0.05). Loss of force production was due to fewer strongly bound cross-bridges in both MHC I (22% + 5.64 younger, 47% + 2.89 older, p < 0.05) and MHC II (25% + 8.17 younger, 40% + 8.52 older, p > 0.05) fibers. However, myosin-actin cross-bridge kinetics, the myosin rate of force production and myosin attachment time, slowed with fatigue only in older muscle, in both MHC isoforms (Figure; brackets indicate significant differences between conditions, p < 0.05). n MHC I fibers from older adults, myofilament stiffness increased with fatigue (60% + 5.13 older), which should increase their ability to produce force and reduce the effects of fatigue. CONCLUSION: Findings indicate fatigue alters molecular contractile function differently with age, which may lead to changes in whole muscle performance. Specifically, in fatigued older muscle, slower myosin-actin cross-bridge kinetics could reduce single fiber contractile velocities and power production, thus contributing to these deficits at the whole muscle level, while the increased stiffness in MHC I fibers may improve their ability to produce force. NIH R01 AG058607