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β1-Adrenergic receptor blockade extends the life span of Drosophila and long-lived mice

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Abstract

Chronic treatment with β-adrenergic receptor (βAR) agonists increases mortality and morbidity while βAR antagonists (β-blockers) decrease all-cause mortality for those at risk of cardiac disease. Levels of sympathetic nervous system βAR agonists and βAR activity increase with age, and this increase may hasten the development of age-related mortality. Here, we show that β-blockers extend the life span of healthy metazoans. The β-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 β-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, βAR 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 β-blockers, which are generally well-tolerated, may enhance the longevity of healthy humans.

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Acknowledgments

The authors thank Ms Carol Boyd for her help in feeding and monitoring the mice, and Ms Amber Graham, Karla Mabida, Sheena Tran, Tracy Nguyen, and Bianca Mabida, and Mr. Kenneth P. Ablao for their technical help with the studies. This work was funded by Alva, LLC, whose business is funding research. The funding organization and its members had no role in study design, data collection or analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Biochemistry, University of California at Riverside, Riverside, CA, 92521, USA

    Stephen R. Spindler, Patricia L. Mote, Rui Li, Joseph M. Dhahbi, Amy Yamakawa, Rui Li & Alex L. Lublin

  2. Department of Statistics, University of California at Riverside, Riverside, CA, 92521, USA

    James M. Flegal & Daniel R. Jeske

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  1. Stephen R. Spindler
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  2. Patricia L. Mote
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Correspondence to Stephen R. Spindler.

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Spindler, S.R., Mote, P.L., Li, R. et al. β1-Adrenergic receptor blockade extends the life span of Drosophila and long-lived mice. AGE 35, 2099–2109 (2013). https://doi.org/10.1007/s11357-012-9498-3

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