Age-related Changes in Motor Function (I). Mechanical and Neuromuscular Factors

This two-part narrative review aims to provide an insight into the age-related mechanical and neuromuscular factors contributing to: (1) decreased maximal muscle strength and power; (2) decreased force control; and (3) increased fatigability. Structural and functional changes from the macro-level of the muscle-tendon unit to the micro-level of the single muscle fibre have been reviewed and are described. At the muscle-tendon unit level, muscle volume, thickness and cross-sectional area, as well as pennation angle and fascicle length all decrease as part of the natural ageing process. These changes negatively affect muscle quality, muscle and tendon stiffness and Young’s modulus and account for impairment in motor performance. A progressive age-related alteration in neuromuscular function is also well-established, with reduction in number and firing rate of the motor unit, contractile velocity and specific tension of muscle fibres, and stability of neuromuscular junction. These could be the result of structural alterations in the: (i) motor neuron, with number reduced, size and collateral sprouting increased; (ii) neuromuscular junction, with decreased post-synaptic junctional fold and density of active zones and increased pre-synaptic branching and post-synaptic area; and (iii) muscle fibre, with decreased number and size and increased type I and co-expression of myosin heavy chain.

Maintenance of skeletal muscle function following reduced daily physical activity in healthy older adults: a pilot trial

Older adults can experience periods of inactivity related to disease or illness, which can hasten the development of physical disability, in part, through reductions in skeletal muscle strength and power. To date no study has characterized adaptations in skeletal muscle physical function in response to reduced daily physical activity. Participants (15 men, aged 69 ± 2 years; 15 women, aged 68 ± 4 years) restricted their daily steps (<750 steps/day) while being energy restricted (–500 kcal/day) for 2 weeks before returning to normal activity levels during recovery (RC; 1 week). Before and after each phase, measures of knee extensor isometric maximum voluntary contraction (MVC), time-to-peak torque, and physical function were performed and muscle biopsies were taken from a subset of participants. Following the energy restriction and step-reduction phase (ER+SR), MVC was reduced by 9.1 and 6.1 Nm in men and women, respectively (p = 0.02), which returned to baseline after RC in men, but not women (p = 0.046). Maximum isometric tension in MHC IIA fibres (p < 0.01) and maximum power production in MHC I and IIA (p = 0.05) were increased by 14%, 25%, and 10%, respectively, following ER+SR. Reductions in muscle strength could not be explained by changes in single muscle fibre function in a subsample (n = 9 men) of volunteers. These data highlight the resilience of physical function in healthy older men in the face of an acute period of ER+SR and demonstrate sex-based differences in the ability to recover muscle strength upon resumption of physical activity.

Understanding mitochondrial DNA maintenance disorders at the single muscle fibre level

Clonal expansion of mitochondrial DNA (mtDNA) deletions is an important pathological mechanism in adults with mtDNA maintenance disorders, leading to a mosaic mitochondrial respiratory chain deficiency in skeletal muscle. This study had two aims: (i) to determine if different Mendelian mtDNA maintenance disorders showed similar pattern of mtDNA deletions and respiratory chain deficiency and (ii) to investigate the correlation between the mitochondrial genetic defect and corresponding respiratory chain deficiency. We performed a quantitative analysis of respiratory chain deficiency, at a single cell level, in a cohort of patients with mutations in mtDNA maintenance genes. Using the same tissue section, we performed laser microdissection and single cell genetic analysis to investigate the relationship between mtDNA deletion characteristics and the respiratory chain deficiency. The pattern of respiratory chain deficiency is similar with different genetic defects. We demonstrate a clear correlation between the level of mtDNA deletion and extent of respiratory chain deficiency within a single cell. Long-range and single molecule PCR shows the presence of multiple mtDNA deletions in approximately one-third of all muscle fibres. We did not detect evidence of a replicative advantage for smaller mtDNA molecules in the majority of fibres, but further analysis is needed to provide conclusive evidence.