Calcium-Handling Defects and Changes in Cardiac Function in the Aging Heart
Individuals aged 70 years or older represent a major population group with a higher risk for myocardial infarction and heart failure. A wide variety of factors have been considered to underlie the phenotype of the aging heart; however, alterations in Ca 2+-handling appear to be of critical importance in the progression of heart dysfunction due to aging. In fact, changes in gene expression, protein content, and activity of the Ca2+-handling proteins such as sarcolemmal (SL) Ca2+-channels and Na+–Ca2+ exchanger as well as sarcoplasmic reticular Ca2+-pump and Ca2+-release channels have been reported in aging hearts. These defects in Ca2+-handling proteins as well as the impaired interaction of Ca2+ with myofibrils in the aging heart are similar to the alterations that occur in younger individuals with heart failure due to hypertension or myocardial infarction. This chapter addresses some of the mechanisms of defects in Ca2+-handling that produce a deregulation of excitation–contraction coupling (ECC), excitation–metabolism coupling (EMC), and excitation–transcription coupling (ETC) in the senescent heart resulting in ventricular arrhythmias, impaired contractile function, and cardiac remodeling in the aging heart. In addition, it is likely that Ca2+-handling abnormalities are attributable to oxidative stress and changes in membrane compositions due to the aging process. Accordingly, it is suggested that some of the interventions which reduce oxidative stress and slow the progression of aging-induced defects in Ca2+-handling improve function of the aging heart.
KeywordsSarcoplasmic Reticulum Diastolic Dysfunction Aging Heart Handling Protein Increase Reactive Oxygen Species Formation
The research in this article was supported by a grant from the Canadian Institute of Health Research (CIHR) and Slovak Scientific Grant Agency (VEGA) 1/0638/12. The infrastructural support for this study was provided by the St. Boniface Hospital Research Foundation. Dr. N.S. Neki was a Visiting Professor from the Government Medical College, Amritsar, India.
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