ß1-Adrenergic receptor blockade extends the life span of Drosophila and long-lived mice

Abstract

Chronic treatment with ß-adrenergic receptor (ßAR) agonists increases mortality and morbidity while ßAR antagonists (ß-blockers) decrease allcause mortality for those at risk of cardiac disease. Levels of sympathetic nervous system ßAR agonists and ßAR activity increase with age, and this increase may hasten the development of age-related mortality.Here, we show that ß-blockers extend the life span of healthy metazoans. The ß-blockers metoprolol and nebivolol, administered in food daily beginning at 12 months of age, significantly increase the mean and median life span of isocalorically fed, male C3B6F1 mice, by 10 and 6.4 %, respectively (P< 0.05). Neither drug affected the weight or food intake of the mice, indicating that induced CR is not responsible for these effects, and that energy absorption and utilization are not altered by the drugs. Both ß- blockers were investigated to control for their idiosyncratic, off-target effects. Metoprolol and nebivolol extended Drosophila life span, without affecting food intake or locomotion. Thus, ßAR antagonists are capable of directly extending the life span of two widely divergent metazoans, suggesting that these effects are phylogenetically highly conserved. Thus, long-term use of ß-blockers, which are generally well-tolerated, may enhance the longevity of healthy humans. © American Aging Association 2013.