Heart Rhythm Harmony Becomes Discordant as We Age.

Heartbeats are initiated by pacemaker cells within the sinoatrial node (SAN) that generate spontaneous impulses at intervals that resonate around a preferred mean frequency. A coupled-clock system (CCS) intrinsic to individual pacemaker cells, that is modulated by autonomic input, drives SAN normal automaticity. Subcellular and cell-wide mechanisms within the CCS are in "dynamic equilibrium," and never achieve a true steady state. Nanoscale electromagnetic "vibrations" caused by mechanisms intrinsic to the CCS and their autonomic modulation create heartbeat rhythm, ("heartbeat music"). A "Heart-Brain Grand Symphony" (HBGS), that emerges from this "beautiful noise" as the heart beats, is broadcast to the body surface, and its numerous motifs within the symphony can be experienced by tuning into electrocardiogram (EKG) RR-interval variability rhythms. As age increases, one or more of the components of physiologic coupling within the neuroautonomic regulatory sinus node and atrial networks begins to deteriorate, and cacophony emerges within the HBGS, manifested by reductions in the mean rate and rhythm at which the CCS within SAN cells fires action potentials. These subclinical changes in SAN structure and function as age advances become "partners" with pathophysiology that defines clinical SAN and other cardiac tissue diseases, e.g., Sick Sinus Syndrome and atrial fibrillation, and as such age-associated changes in SAN structure and function are co-morbidities of these clinical cardiac diseases. In other terms as age advances, sub-clinical age-associated changes in SAN structure and function, per se, are major shareholders in SAN disease enterprises.