Calcium cycling in the aged heart

One of the most important hallmarks of the aged heart is altered calcium homeostasis, possibly due to age-associated alterations in several major calcium cycling processes involved in cardiac excitation-contraction coupling. During ageing, the magnitude of the L-type Ca²⁺ channel current (I_Ca,L) becomes significantly increased in parallel with the enlargement of cardiac myocytes, resulting in an unaltered I_Ca,L density. Since the inactivation of I_Ca,L is slowed, and the action potential duration is prolonged, the net Ca²⁺ influx during each action potential is increased in cells of senescent myocardium relative to cells of adult control. While neither mRNA nor protein levels of the sarcoplasmic reticulum (SR) Ca²⁺ release channel (ryanodine receptor) significantly change with advancing adult age, the mRNA abundance and the density of SR Cat+ pump decrease with ageing and are associated with a diminished SR Ca²⁺ sequestration rate in the aged heart. In addition, cardiac chronotropic and inotropic responses to β-adrenergic receptor stimulation are also reduced with advancing age. The multiple changes in Ca cycling that occur during ageing result in an augmented Cat+ influx, slowed SR Ca²⁺ sequestration and prolonged durations of the Ca_i transient and contraction. These alterations which prolong electromechanical systole may be construed as an adaptation in that they prolong the force-bearing capacity of the senescent cells following excitation. This is helpful with respect to maintaining the cardiac function in the aged heart. However, they also increase the risk of Ca²⁺ overload and Cat²⁺-dependent arrhythmias during stress in the senescent heart. Although reduced (3-adrenergic responses with ageing contribute to diminished contraction reserve, these may be viewed in part, as adaptive, in that they protect against Ca²⁺ overload during stress.