Acclimation to a thermoneutral environment abolishes age-associated alterations in heart rate and heart rate variability in conscious, unrestrained mice

Mice are among the most widely used translational models of cardiovascular aging and offer a method to quickly assess lifespan changes in a controlled environment. The standard laboratory temperature (20-22 °C), however, imposes a cold stress on mice that causes an increase in sympathetic nervous system-mediated activation of brown adipose tissue (BAT) to maintain a core body temperature of 36-37 °C. Thus, while physiologic data obtained recapitulate human physiology to a certain degree, interpretations of previous research in mice may have been contaminated by a cold stress, due to housing mice below their thermoneutral zone (30 °C). The purpose of this investigation was to examine how chronic sympathetic stimulation evoked by acclimation to 20 °C might obscure interpretation of changes in autonomic modulation of heart rate (HR) and heart rate variability (HRV) that accompany advancing age. HR and HRV before and after administration of a dual-autonomic blockade were measured via in-vivo ECG in young (3 months) and aged (30 months) male C57BL/6 telemetry-implanted mice following temperature acclimation for 3 days at 30 °C or 20 °C. Mean basal and intrinsic HR of both young and aged mice became markedly reduced at 30 °C compared to 20 °C. In both age groups, HRV parameters in time, frequency, and non-linear domains displayed increased variability at 30 °C compared to 20 °C under basal conditions. Importantly, age-associated declines in HRV observed at 20 °C were ameliorated when mice were studied at their thermoneutral ambient temperature of 30 °C. Thus, an accurate understanding of autonomic modulation of cardiovascular functions in mice of advanced age requires that they are housed in a metabolically neutral environment.