Heart Rate Reduction and Longevity in Mice

Abstract

BackgroundHeart rate correlates inversely with life span across all species, including humans. In patients with cardiovascular disease, higher heart rate is associated with increased mortality, and such patients benefit from pharmacological heart rate reduction. However, cause‐and‐effect relationships between heart rate and longevity, notably in healthy individuals, are not established. We therefore prospectively studied the effects of a life‐long pharmacological heart rate reduction on longevity in mice. We hypothesized, that the total number of cardiac cycles is constant, and that a 15 % heart rate reduction might translate into a 15 % increase in life span.Methods: C57BL6/J mice received either placebo or ivabradine at a dose of 50 mg/kg/day in drinking water from 12 weeks to death. Heart rate and body weight were monitored. Autopsy was performed on all non‐autolytic cadavers, and parenchymal organs were evaluated macroscopically.Results: Ivabradine reduced heart rate by 14 (median, interquartile range 12 to 15) % throughout life, and median life span was increased by 6.2 % (p=0.01). An inverse relationship existed between individual heart rate and life span in all tested mice (r=0.86; p=0.046). Body weight and macroscopic findings were not different between placebo and ivabradine.ConclusionLife span was not increased by the same extent as heart rate was reduced, but nevertheless significantly prolonged by 6.2 %, which in humans translates to an additional 5 years for a person of 80 years.