Decreased pacemaker activity in aged sinoatrial node

National Institute On Aging

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Abstract

The results of this study are currently being analyzed. To this end we have implemented a longitudinal study to measure basal and intrinsic HR and HRV via EKG in mice every 3 months from 6 months of age until death. The longitudinal measurements are being analyzed using linear mixed-effects models. The models chosen allowed for a change in the form of the relationship before and after the median lifespan (21 mo.). Since most changes in HR and HRV parameters occur after about 21 months, the current analyses restrict attention to long-lived mice those that live beyond the median lifespan. In addition, the mouse-specific rates of change are being estimated from the models and the associations among these rates of change are determined for the various parameters measured. Longer lived mice displayed relatively minor changes in intrinsic RR interval variability or mean intrinsic RR interval prior to 21 months of age. But between 21 and 30 months of age, the average cohort mean intrinsic RR interval increased dramatically due to marked changes in intrinsic RR interval variability that included: (1) an increase in the standard deviation of the mean intrinsic RR interval (SDRR), resulting from increased variability in both intrinsic short range (SD1) and long range (SD2) RR interval correlations within the RR interval time series; (2) an increase in non-linearity of RR interval variability within long and short range RR interval correlations (decreased (SD1:SD); (3) a shift from high frequency (HF) to very low frequency components of total intrinsic power; (4) an increase in intrinsic detrended fluctuation analysis (DFA) long range coefficient 2; (5) increased long range intrinsic RR interval fragmentation, reflected in increases in the percentage of alternating long-short segments (PAS). The rates at which %VLF power, DFA 2 and PAS increased, and the mouse-specific rates at which %HF power and SD1 and SD2 became reduced were significantly correlated with the rate at which the mean RR interval in that mouse increased during advanced age. Autonomic input partially compensated for the age-associated deterioration by reducing RR interval variability that was associated with a reduction in the mean RR interval toward their basal levels. In other terms, the net effect of autonomic input to the SAN of long-lived mice of advanced age mimicked augmented sympathetic input, thereby enhancing coherence and reducing the complex disorder within intrinsic EKG RR interval time-series. Thus, beyond 21 mo. of age, marked changes in intrinsic RR interval variability in time, frequency, nonlinear and fragmentation domains subtended a marked increase in the mean intrinsic RR interval. In addition, in cross-sectional analyses of other subsets of mice at ages at or beyond the median life span of our longitudinal cohort demonstrated: an increase in a non-cardiac, constitutional, whole body frailty index; a decrease in energetic efficiency; and an increase in respiratory exchange ratio. In this context, we interpret the results of our longitudinal analysis of EKG interval time-series to indicate that the progressive increase in intrinsic RR interval variability beyond 21 mo. of age that subtends a progressive increase in the mean intrinsic RR interval beyond this age is an indication of heartbeat frailty.