CARDIAC GENE EXPRESSION WITH ADULT AGING

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Cardiac muscle of senescent rodent hearts exhibits cardiac cell enlargement and a pattern of altered cardiac excitation-contraction mechanisms, among which are a reduced contraction velocity, a reduction in the myosin ATPase activity, a prolonged contraction time and a reduced rate of Ca2+ sequestration into isolated sarcoplasmic reticulum (SR). The present study was undertaken to determine whether the age-associated phenotypic changes are also associated with changes in myosin heavy chain (MHC) or SR Ca ATPase gene expression. Levels of mRNA coding for alpha and beta MHC, SR Ca ATPase, calsequestrin, an SR Ca2+ binding protein, and the alpha-skeletal and cardiac isoforms of actin were determined by Northern analysis and dot blots on RNA purified from 6 hearts each, of animals of a broad age range. The mRNA for beta MHC increased greater than fourfold from 1 to 24 months, the alpha mRNA for alpha MHC decreased by a proportional amount. The mRNA for SR Ca ATPase decreased by 50% from 12-24 mo. Neither calsequestrin nor `-skeletal or cardiac actin isoforms changed with adult age. Additionally, S1 nuclease mapping analysis revealed that neither the Ca2+-ATPase nor the calsequestrin gene products expressed in heart were differentially spliced during aging. Thus, the phenotypic, biophysical and biochemical cardiac contractile changes with adult aging are, in part at least, transcriptionally regulated: the MHC isogene shift produces different isoforms of MHC proteins. Actin isogenes do not differentially express their products with adult aging. While the level of the SR mRNA declines with senescence there is no evidence for an isoform shift. The Ca binding protein gene, calsequestrin does not appear to change its expression or isoform with aging.