Altered Intracellular Calcium Homeostasis and Arrhythmogenesis in the Aged Heart

Abstract

Aging of the heart is associated with a blunted response to sympathetic stimulation, reduced contractility, and increased propensity for arrhythmias, with the risk of sudden cardiac death significantly increased in the elderly population. The altered cardiac structural and functional phenotype, as well as age-associated prevalent comorbidities including hypertension and atherosclerosis, predispose the heart to atrial fibrillation, heart failure, and ventricular tachyarrhythmias. At the cellular level, perturbations in mitochondrial function, excitation-contraction coupling, and calcium homeostasis contribute to this electrical and contractile dysfunction. Major determinants of cardiac contractility are the intracellular release of Ca2+ from the sarcoplasmic reticulum by the ryanodine receptors (RyR2), and the following sequestration of Ca2+ by the sarco/endoplasmic Ca2+-ATPase (SERCa2a). Activity of RyR2 and SERCa2a in myocytes is not only dependent on expression levels and interacting accessory proteins, but on fine-tuned regulation via post-translational modifications. In this paper, we review how aberrant changes in intracellular Ca2+ cycling via these proteins contributes to arrhythmogenesis in the aged heart.

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Examining Cardiomyocyte Dysfunction Using Acute Chemical Induction of an Ageing Phenotype

“…Whilst there may not be an absolute overlap between the features of naturally aged cardiomyocytes and HU-treated cells, there are a number of key parameters that are found in both situations. It is notable that although longitudinal or comparative studies using young versus aged animals are generally considered to be optimal for investigating ageing, they do not always reach the same conclusions, particularly with respect to changes in the heart [2]. Chemical models that evoke ageing-relevant changes, therefore, deserve further attention as they may provide tractable and relatively inexpensive systems for analysis of cellular systems and their dysfunctions that lead to morbidity and mortality.…”

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Variation of Tpeak‐end, corrected Tpeak‐end, QT, and corrected QT intervals, Tpeak‐end/QT, Tpeak‐end/corrected QT ratios and heart rate variability according to decades in the healthy male subjects aged between 30 and 79 years

“…Aging of the heart is associated with a blunted response to sympathetic stimulation, reduced contractility, and an increased propensity for arrhythmias, with the risk of malign ventricular arrhythmia, which significantly increased in the elderly population. The altered cardiac structural and functional phenotype, as well as age‐associated prevalent comorbidities, including hypertension and atherosclerosis, predispose the heart to atrial fibrillation, heart failure, and ventricular tachyarrhythmias 3 …”