Impacts of frailty on heart rate variability in aging mice: Roles of the autonomic nervous system and sinoatrial node

Heart rate variability (HRV) is determined by intrinsic sinoatrial node (SAN) activity and the autonomic nervous system (ANS). HRV is reduced in aging; however, aging is heterogeneous. Frailty, which can be measured using a frailty index (FI), can quantify health status in aging separately from chronological age.The purpose of this study was to investigate the impacts of age and frailty on HRV in mice.Frailty was measured in aging mice between 10 and 130 weeks of age. HRV was assessed using time domain, frequency domain, and Poincaré plot analyses in anesthetized mice at baseline and after ANS blockade, as well as in isolated atrial preparations.HRV was reduced in aged mice (90-130 weeks and 50-80 weeks old) compared to younger mice (10-30 weeks old); however, there was substantial variability within age groups. In contrast, HRV was strongly correlated with FI score regardless of chronological age. ANS blockade resulted in reductions in heart rate that were largest in 90- to 130-week-old mice and were correlated with FI score. HRV after ANS blockade or in isolated atrial preparations was increased in aged mice but again showed high variability among age groups. HRV was correlated with FI score after ANS blockade and in isolated atrial preparations.HRV is reduced in aging mice in association with a shift in sympathovagal balance and increased intrinsic SAN beating variability; however, HRV is highly variable within age groups. HRV was strongly correlated with frailty, which was able to detect differences in HRV separately from chronological age.