The effect of ageing and immobilization on structure and function of human skeletal muscle fibres

Abstract

Biopsy samples were taken from vastus lateralis muscle of seven young (YO, age 30.2 +/- 2.2 years), and seven elderly (EL, age 72.7 +/- 2.3 years) subjects and two elderly subjects whose right leg had been immobilized for 3.5 months (EL-IMM, ages 70 and 75). The following main parameters were studied: (1) myosin heavy chain (MHC) isoform distribution of the samples, determined by SDS-PAGE; (2) cross-sectional area (CSA), specific force (Po/CSA) and maximum shortening velocity (Vo) of a large population (n = 593) of single skinned muscle fibres, classified on the basis of MHC isoform composition determined by SDS-PAGE; (3) actin sliding velocity (Vf) on pure myosin isoforms determined by in vitro motility assays; (4) myosin concentration in single fibres determined by quantitative SDS-PAGE. MHC isoform distribution was shifted towards fast isoforms in EL and to a larger extent in EL-IMM. In EL and, more consistently, in EL-IMM we observed a higher percentage of hybrid fibres than in YO, and noted the presence of MHC-neonatal and of unusual hybrid fibres containing more than two MHC isoforms. Po/CSA significantly decreased in type 1 and 2A fibres in the order YO EL EL-IMM. Vo of type 1 and 2A fibres was significantly lower in EL and higher in EL-IMM than in YO, i.e. immobilization more than counteracted the age-dependent decrease in Vo. The latter phenomenon was not observed for Vf. Vf on myosin 1 was lower in both EL and EL-IMM than in YO. Vf on myosin 2X was lower in EL than in YO, and a similar trend was observed for myosin 2A. Myosin concentration decreased in type 1 and 2A fibres in the order YO EL EL-IMM and was linearly related to the Po/CSA values of corresponding fibre types from the same subjects. The experiments suggest that (1) myosin concentration is a major determinant of the lower Po/CSA of single fibres in ageing and especially following immobilization and (2) ageing is associated with lower Vo of single fibres due to changes in the properties of myosin itself, whereas immobilization is associated with higher Vo in the absence of a change in myosin function.

Skeletal muscle contractile protein function is preserved in human heart failure

“…4A, a decrease in MHC protein content would reduce muscle force production. A similar relationship of MHC protein content to muscle force production has been demonstrated in human single muscle fibers (6,14). In this context, and in light of the current results, we put forth the hypothesis that skeletal muscle contractile dysfunction in heart failure (26) patients is caused by reduced MHC protein content rather than by alterations in the function of individual contractile proteins.…”

Age-related muscle dysfunction

“…Furthermore, the decline in MHC in the semimembranosus muscle supports the agerelated muscle specific phenotype (fast-twitch versus slow-twitch discussed earlier). Interestingly, age-related changes of myosin concentration were also indicated as a major determinant of changes in P 0 of human vastus lateralis muscle (D'Antona et al, 2003).…”

Predictive factors for spasticity among ischemic stroke patients

“…Spasticity was not associated with gender, age, race/ color, marital status, schooling level, status within professional occupation, social class or sports activities. Our initial hypothesis was that constitutional and functional characteristics relating to sex, age and ethnicity might be associated with differences in the prevalence of spasticity, due to alterations in the proportions, quantities, distribution and type of muscle fibers at different ages 14,16,25,26 .…”