Effect of age on cardiac excitation-contraction coupling

P>1. Cardiovascular diseases most commonly occur in the elderly and are a frequent cause of disability or death. However, the effect of age itself on cardiac function is not well understood. 2. Studies in both human and animal hearts indicate that contractile function is unaffected by age while at rest. However, the ability to increase cardiac contractile force during strenuous activities, such as exercise, declines with age. 3. Similar findings have been observed in individual ventricular myocytes isolated from aged hearts. When myocytes are stimulated with beta-adrenoceptor agonists or rapid pacing frequencies, aged cells show a much smaller increase in peak contractions and Ca2+ transients than young adult cells. In addition, contractions and Ca2+ transients are prolonged in aged cells compared with younger cells under these conditions. 4. These observations suggest that the age-related decline in cardiac contractile function originates at the cellular level and may reflect modifications in processes involved in excitation-contraction (EC) coupling. 5. Biochemical studies have shown that there are age-related modifications in the expression, regulation and function of a number of proteins essential to EC coupling in the heart. 6. Functional studies indicate that these changes in EC coupling proteins disrupt Ca2+ homeostasis and contribute to decrease in peak contraction and prolongation of contraction duration observed in myocytes from aged hearts. 7. The present review describes modifications in cardiac contractile function that occur in the ageing heart and evaluates underlying alterations in the EC coupling pathway that may be responsible for this decline in contractile function in ageing.