Sarcoplasmic reticulum in aged skeletal muscle.

Abstract

A decrease in muscle mass and strength and a slowing of muscle contraction are common features of the ageing process. Recent advances in basic biochemical knowledge have provided new insights into pathogenetic mechanisms underlying age-related changes in the excitation-contraction coupling process, Ca2+-transients and isometric twitch-contraction time. Sarcoplasmic reticulum (SR) Ca2+-pumps are not basically altered in physiological ageing, but several aspects of the Ca2+-transport system remain controversial, regarding phosphorylation-dependent regulation in slow-twitch muscles, in particular. It seems that conflicting reports and divergent interpretations concerning the effect of ageing on SR Ca2+-release arise from the type of muscle, the stage of the ageing process and the animal species. A cause-effect relationship between the decrease in dihydropyridine receptors and in muscle strength is strongly suggested by studies in transgenic mice, but is unsupported by our studies with fast-twitch and slow-twitch muscles of old rats. Our experimental evidence also seems to exclude the occurrence of age-related changes in the number and in the functional behaviour of Ca2+-release channels/ryanodine receptors (RyR1), based on ¿3H-ryanodine binding studies. There is emerging, although only suggestive evidence, so far, that modulation of RyR1 by SR luminal protein calsequestrin, or the functional coupling of RyRs by FKBP-12, may be altered in ageing skeletal muscle.