Contractile properties and sarcoplasmic reticulum calcium content in typeI and typeII skeletal muscle fibres in active aged humans.

Abstract

Muscle weakness in old age is due in large part to an overall loss of skeletal muscle tissue, but it remains uncertain how much also stems from alterations in the properties of the individual muscle fibres. This study examined the contractile properties and amount of stored intracellular calcium in single muscle fibres of Old (70±4years) and Young (22±3years) adults. The maximum level of force production (per unit cross-sectional area) in fast twitch fibres in Old subjects was lower than in Young subjects, and the fibres were also less sensitive to activation by calcium. The amount of calcium stored inside muscle fibres and available to trigger contraction was also lower in both fast- and slow-twitch muscle fibres in the Old subjects. These findings indicate that muscle weakness in old age stems in part from an impaired capacity for force production in the individual muscle fibres. This study examined the contractile properties and sarcoplasmic reticulum (SR) Ca(2+) content in mechanically skinned vastus lateralis muscle fibres of Old (70±4years) and Young (22±3years) humans to investigate whether changes in muscle fibre properties contribute to muscle weakness in old age. In typeII fibres of Old subjects, specific force was reduced by ∼17% and Ca(2+) sensitivity was also reduced (pCa50 decreased ∼0.05pCa units) relative to that in Young. S-Glutathionylation of fast troponinI (TnIf ) markedly increased Ca(2+) sensitivity in typeII fibres, but the increase was significantly smaller in Old versus Young (+0.136 and +0.164pCa unit increases, respectively). Endogenous and maximal SR Ca(2+) content were significantly smaller in both typeI and typeII fibres in Old subjects. In fibres of Young, the SR could be nearly fully depleted of Ca(2+) by a combined caffeine and low Mg(2+) stimulus, whereas in fibres of Old the amount of non-releasable Ca(2+) was significantly increased (by >12% of endogenous Ca(2+) content). Western blotting showed an increased proportion of typeI fibres in Old subjects, and increased amounts of calsequestrin-2 and calsequestrin-like protein. The findings suggest that muscle weakness in old age is probably attributable in part to (i) an increased proportion of typeI fibres, (ii) a reduction in both maximum specific force and Ca(2+) sensitivity in typeII fibres, and also a decreased ability of S-glutathionylation of TnIf to counter the fatiguing effects of metabolites on Ca(2+) sensitivity, and (iii) a reduction in the amount of releasable SR Ca(2+) in both fibre types.