Regulatory mechanisms range from a single level of control in simple metazoans to multi-level hierarchical control networks in higher animals. Organismal regulation encompasses homeostatic and circadian networks that are interconnected, with no documented exceptions. The epigenetic clock is a highly accurate biomarker of age in humans, defined by a mathematical algorithm based on the methylation of a subset of age-related CpG sites on DNA. Experimental evidence suggests the existence of an underlying regulatory mechanism. By analogy with other integrative systems as the neuroendocrine-immune network and the circadian clocks, a hierarchical organization in the control of the ticking rate of the epigenetic clock is hypothesized here. The hierarchical organization of the neuroendocrine, immune and circadian systems is briefly reviewed. This is followed by a brief review of the epigenetic clock at cell level. Finally, different lines of indirect evidence, consistent with the existence of a central pacemaker controlling the ticking rate of the epigenetic clock at organismal level are discussed. The concluding remarks put the hierarchical model proposed for the control of the clock into an evolutionary perspective. Within this perspective, the present hypothesis is intended as a conceptual outline based on designs consistently favored by evolution in higher animals.

调节机制的范围从简单后生动物的单一控制到高级动物的多层控制网络。有机体法规包括相互联系的体内稳态和昼夜节律网络，没有任何文件记载的例外情况。表观遗传时钟是人类年龄的高度精确生物标志物，通过数学算法定义，该数学算法基于DNA上与年龄相关的CpG位点的子集的甲基化。实验证据表明存在潜在的调节机制。通过与其他集成系统（如神经内分泌免疫网络和生物钟）的类比，在此假设了表观遗传钟的滴答率控制中的分层组织。简要回顾了神经内分泌，免疫和昼夜节律系统的层次结构。接下来是对细胞水平的表观遗传时钟的简要回顾。最后，讨论了不同的间接证据，与在生物体水平上控制表观遗传时钟的滴答频率的中央起搏器的存在相一致。结束语将提出用于时钟控制的分层模型放到了进化的角度。在这种观点下，本假设旨在作为基于高等动物进化一贯支持的设计的概念概述。结束语将提出的用于时钟控制的分层模型放到了进化的角度。在这种观点下，本假设旨在作为基于高等动物进化一贯支持的设计的概念概述。结束语将提出用于时钟控制的分层模型放到了进化的角度。在这种观点下，本假设旨在作为基于高等动物进化一贯支持的设计的概念概述。