The cardiac pacemaker ignites and coordinates the contraction of the whole heart, uninterruptedly, throughout our entire life. Pacemaker rate is constantly tuned by the autonomous nervous system to maintain body homeostasis. Sympathetic and parasympathetic terminals act over the pacemaker cells as the accelerator and the brake pedals, increasing or reducing the firing rate of pacemaker cells to match physiological demands. Despite the remarkable reliability of this tissue, the pacemaker is not exempt from the detrimental effects of aging. Mammals experience a natural and continuous decrease in the pacemaker rate throughout the entire lifespan. Why the pacemaker rhythm slows with age is poorly understood. Neural control of the pacemaker is remodeled from birth to adulthood, with strong evidence of age-related dysfunction that leads to a downshift of the pacemaker. Such evidence includes remodeling of pacemaker tissue architecture, alterations in the innervation, changes in the sympathetic acceleration and the parasympathetic deceleration, and alterations in the responsiveness of pacemaker cells to adrenergic and cholinergic modulation. In this review, we revisit the main evidence on the neural control of the pacemaker at the tissue and cellular level and the effects of aging on shaping this neural control.

心脏起搏器在我们的整个生命中不间断地点燃并协调整个心脏的收缩。起搏器频率由自主神经系统不断调整，以维持身体稳态。交感神经和副交感神经末梢作为加速器和制动踏板作用于起搏器细胞，增加或降低起搏器细胞的放电率以满足生理需求。尽管这种组织具有显着的可靠性，但起搏器也不能免于老化的不利影响。在整个生命周期中，哺乳动物的起搏器频率会自然而持续地下降。为什么起搏器节律随着年龄的增长而减慢尚不清楚。起搏器的神经控制从出生到成年都进行了改造，有强有力的证据表明与年龄相关的功能障碍会导致起搏器降档。这些证据包括起搏器组织结构的重塑、神经支配的改变、交感神经加速和副交感神经减速的变化，以及起搏器细胞对肾上腺素能和胆碱能调节的反应性改变。在这篇综述中，我们重新审视了起搏器在组织和细胞水平上的神经控制的主要证据，以及衰老对塑造这种神经控制的影响。