Remodeling of the intercalated disc related to aging in the XXXX heart.

@entity19 @entity16899 @entity21043 @entity299
BACKGROUND: Aging is related to declined cardiac hemodynamic function. As pumping performance may be significantly related to slowed ventricular depolarization and non-synchronous contraction, we hypothesized that aging may cause dysfunction of intercalated disc (ID), which is the structure responsible for intercellular electrical communication between cardiomyocytes. METHODS: Male C57BL/6J @entity19 were used for the study at two ages: 4 and 24 months. Electrocardiographic recording was made to analyze the time of ventricular depolarization. Then @entity19 were killed, and the hearts were harvested for examination in transmission electron microscopy (TEM) and immunofluorescence imaging. The expression of @entity16899 ( @entity16899 ), @entity21043 , and b-catenin in the myocardium of the left ventricle was evaluated using Western blotting. RESULTS: In senescent @entity19 , analysis of averaged QRS complex showed its significant prolongation. At the ultrastructural level, we found frequent disruptions of the ID (affecting 29  5% of them), mainly at the site of adherens junction, with relatively preserved desmosomal intercellular connections and diminished number of gap junctions. Western blotting revealed significantly decreased abundance of @entity16899 protein in aged animals, which may cause slowed impulse propagation through the gap junctions and contribute to the observed electrocardiographic alterations. The level of RNA for @entity16899 is similar between young and old animals, which suggests a post-transcriptional mechanism of @entity16899 protein downregulation. CONCLUSIONS: Our study shows age-related disorganization of ID, which may be responsible for slowed conduction of the depolarization wave within the heart, and supports the hypothesis of @entity299 in senescence.
