“…The root cause of these changes is not completely understood, but several lines of evidence indicate reduced myocardial β-adrenergic receptor density, their functional decline, and deficits in the β-adrenergic signaling cascade with advanced age [48,64,65]. Interestingly, Drosophila express components homologous to those of the vertebrate pathway, including adrenergic-like octopamine receptors (OctαRs, and OctβRs), adenylyl cyclase (rutabaga), phosphodiesterase (dunce), and both regulatory and catalytic subunits of protein kinase A (PKA), and their cardiac L-type calcium channels exhibit PKA-mediated current enhancement [60]. The expression of all aforementioned genes uniformly declines with age in Drosophila cardiomyocytes [15,24,66], suggesting old fly hearts may also exhibit blunted responses to adrenergic stimulation.…”