Long-term α1B-adrenergic receptor activation shortens lifespan, while α1A-adrenergic receptor stimulation prolongs lifespan in association with decreased cancer incidence

The alpha(1)-adrenergic receptor (alpha(1)AR) subtypes, alpha(1A)AR and alpha(1B)AR, have differential effects in the heart and central nervous system. Long-term stimulation of the alpha(1A)AR subtype prolongs lifespan and provides cardio- and neuro-protective effects. We examined the lifespan of constitutively active mutant (CAM)-alpha(1B)AR mice and the incidence of cancer in mice expressing the CAM form of either the alpha(1A)AR (CAM-alpha(1A)AR mice) or alpha(1B)AR. CAM-alpha(1B)AR mice have a significantly shortened lifespan when compared with wild-type (WT) animals; however, the effect was sex dependent. Female CAM-alpha(1B)AR mice lived significantly shorter lives, while the median lifespan of male CAM-alpha(1B)AR 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-alpha(1B)AR mice. The incidence of cancer was significantly decreased in CAM-alpha(1A)AR 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 alpha(1)AR subtype and the effect of sex on lifespan following activation of the alpha(1B)AR. The implications of a decrease in cancer incidence following long-term alpha(1A)AR stimulation could lead to improved treatments for cancer.