Emergence of heartbeat frailty in advanced age I: perspectives from life-long EKG recordings in adult mice

• DOI: 10.1007/s11357-022-00605-4
• Publication Date: 2022-06-27T12:04:43Z
• Authors: Jack M. Moen; Christopher H. Mo...; Michael G. Matt; Ismayil Ahmet; Syevda Tagirova; Moran Davoodi; Michael Petr; Shaquille Charles; Rafael de Cabo; Yael Yaniv; Edward G. Lakatta
• Keywords: RR interval

The combined influences of sinoatrial nodal (SAN) pacemaker cell automaticity and its response to autonomic input determine the heart's beating interval variability mean rate. To intrinsic SAN signatures buried within EKG RR time series change in advanced age, we measured before during double blockade at 3-month intervals from 6 months age until end life long-lived (those that achieved total cohort median span 24 beyond) C57/BL6 mice. Prior 21 time-dependent changes were relatively minor. Between 30 however, marked emerged signatures, pointing a reduction kinetics clock mechanisms, leading reduced synchronization molecular functions among cells. This loss high-frequency signal processing resulted increase interval. impact on net sympathetic partially compensated for partially, but not completely, shifted more youthful pattern. Cross-sectional analyses other subsets ages indicated or beyond our longitudinal cohort, noncardiac, constitutional, whole-body frailty was increased, energetic efficiency reduced, respiratory exchange ratio increased. We interpret progressive this context be manifestation "heartbeat frailty."