The broad objective of this program is to perform preclinical experimentation on animal models of aging to elucidate the possible biomarkers that strongly associated with health span and lifespan of mouse. For that purpose, we used echocardiography to observed cardiac and vascular physiological parameters non-invasively in a cohort of 58 mice from 3 months of age to their natural deaths of everyone in a 3-month interval. We also recorded ECG with and without autonomic blockade to elucidate the changes with intrinsic heart rate by age. Preliminary results indicated that regardless of absolute lifespan of mice, most of the cardiac and vascular physiological parameters we observed showed clear longitudinal trajectories when adjusted to percent of lifespan that calculated retrospectively for each individual subject. From these trajectories, lifespan of an individual subject may be predicted. On the other hand, trajectories of HR, Intrinsic HR and HRV showed clear age-associated changes in brain adrenergic drive, increases in sympathetic drive while reduction in parasympathetic drive, by age in mice. The relationship between gene expression profile of SAN and changes in intrinsic HR and HRV are currently under investigation.
|Yaniv, Yael; Ahmet, Ismayil; Tsutsui, Kenta et al. (2016) Deterioration of autonomic neuronal receptor signaling and mechanisms intrinsic to heart pacemaker cells contribute to age-associated alterations in heart rate variability in vivo. Aging Cell 15:716-24|