Student thesis: Doctoral ThesisDoctor of Philosophy


The loss of muscle strength in the elderly is greater than the loss of muscle mass, termed specific force (SF) loss, and indicates that a decrease in muscle quality contributes to age-related muscular weakness. The present PhD thesis has studied age-related SF loss in human skeletal muscle using a skinned single muscle fibre model. A large variation in published skinned fibre SF measurements was found to exist in the literature. Therefore, a systematic review and meta-analysis was performed to identify factors causing this variability. The majority of publications were objectively divided into four research groups based on shared authorship. Methodological differences between research groups contributed to ~30% of the variance in the literature, suggesting that they are an important contributor to the variance in published SF values. Different research groups use different activating solutions to study skinned fibres, and were assessed experimentally. Skinned fibres were exposed to different, but commonly used activating solutions (termed A and B). A significantly higher SF and a shorter time to half peak tension (t50) was measured from the same fibres in solution B compared with solution A. The use of TES in solution B instead of Imidazole as a pH buffer largely caused the SF difference, and a lower Cl- concentration and the use of Glutathione in solution B partly caused the faster t50. These findings indicate that the use of different activating solutions likely affects the variance of published SF values. The final study in this thesis compared SF between skinned fibres from physically active and comparatively frail elderly cohorts to a young, healthy group. MHC I fibre SF was significantly higher in solution B than A within all groups. No significant differences in SF, myosin content (SDS PAGE) or order (X-ray diffraction) were observed between groups. These findings suggest that physical activity does not affect age-related skinned fibre SF loss and that SF is related to skinned fibre myosin content.
Date of Award2017
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorStephen Harridge (Supervisor) & Julien Ochala (Supervisor)

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