title: Heart rate reduction and longevity in mice.
abstract: Heart 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. 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. Ivabradine reduced heart rate by 14% (median, interquartile range 12-15%) throughout life, and median life span was increased by 6.2% (p = 0.01). Body weight and macroscopic findings were not different between placebo and ivabradine. Life span was not increased to the same extent as heart rate was reduced, but nevertheless significantly prolonged by 6.2%.
authors.affiliation: Institute for Pathophysiology, West German Heart and Vascular Center, University School of Medicine, Hufelandstr. 55, 45122, Essen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Gent
authors.forename: Petra
authors.initials: P
authors.lastname: Kleinbongard
authors.forename: Philip
authors.initials: P
authors.lastname: Dammann
authors.forename: Markus
authors.initials: M
authors.lastname: Neuhäuser
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D000077550:Ivabradine; D008136:Longevity / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology
chemical_list: D001552:Benzazepines; D002317:Cardiovascular Agents; D000077550:Ivabradine