Abstract
The α1-adrenergic receptor (α1AR) subtypes, α1AAR and α1BAR, have differential effects in the heart and central nervous system. Long-term stimulation of the α1AAR subtype prolongs lifespan and provides cardio- and neuro-protective effects. We examined the lifespan of constitutively active mutant (CAM)-α1BAR mice and the incidence of cancer in mice expressing the CAM form of either the α1AAR (CAM-α1AAR mice) or α1BAR. CAM-α1BAR mice have a significantly shortened lifespan when compared with wild-type (WT) animals; however, the effect was sex dependent. Female CAM-α1BAR mice lived significantly shorter lives, while the median lifespan of male CAM-α1BAR mice was not different when compared with that of WT animals. There was no difference in the incidence of cancer in either sex of CAM-α1BAR mice. The incidence of cancer was significantly decreased in CAM-α1AAR mice when compared with that in WT, and no sex-dependent effects were observed. Further study is warranted on cancer incidence after activation of each α1AR subtype and the effect of sex on lifespan following activation of the α1BAR. The implications of a decrease in cancer incidence following long-term α1AAR stimulation could lead to improved treatments for cancer.
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Acknowledgments
This research was supported by an American Physiological Society Undergraduate Research Fellowship (M.J.L.), a University of North Dakota School of Medicine and Health Sciences Undergraduate Research Fellowship (H.M.A.), a National Science Foundation Graduate Research Fellowship DGE-0950693 (K.M.C.), a National Science Foundation Research Experiences for Undergraduates Site grant 0851869 (V.A.D.), an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 GM103442 (D.A.S.), and a grant from the National Institute of Heart, Lung, and Blood R01-HL098279 (D.M.P.). The authors thank Dr. Holly Brown-Borg and Brianna Goldenstein for helpful comments on this manuscript.
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Collette, K.M., Zhou, X.D., Amoth, H.M. et al. Long-term α1B-adrenergic receptor activation shortens lifespan, while α1A-adrenergic receptor stimulation prolongs lifespan in association with decreased cancer incidence. AGE 36, 9675 (2014). https://doi.org/10.1007/s11357-014-9675-7
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DOI: https://doi.org/10.1007/s11357-014-9675-7