Juckett D A
Mech Ageing Dev. 1987 Mar;38(1):49-71. doi: 10.1016/0047-6374(87)90110-2.
A model is presented which proposes a specific cause-and-effect relationship between a limited cell division potential and the maximum lifespan of humans and other mammals. It is based on the clonal succession hypothesis of Kay which states that continually replicating cell beds (e.g. bone marrow, intestinal crypts, epidermis) could be composed of cells with short, well-defined division potentials. In this model, the cells of these beds are proposed to exist in an ordered hierarchy which establishes a specific sequence for cell divisions throughout the organism's lifespan. The depletion of division potential at all hierarchical levels leads to a loss of bed function and sets an intrinsic limit to species longevity. A specific hierarchy for cell proliferation is defined which allows the calculation of time to bed depletion and, ultimately, to organism mortality. The model allows the existence of a small number (n) of critical cell beds within the organism and defines organism death as the inability of any one of these beds to produce cells. The model is consistent with all major observations related to cellular and organismic aging. In particular, it links the PDLs (population doubling limit) observed for various species to their mean lifespan; it explains the slow decline in PDL as a function of age of the donor; it establishes a thermodynamically stable maximum lifespan for a disease-free population; and it can explain why tissue transplants outlive donors or hosts.
本文提出了一个模型，该模型提出了有限的细胞分裂潜能与人类和其他哺乳动物的最大寿命之间的特定因果关系。它基于凯的克隆 succession 假说，该假说指出持续复制的细胞群（如骨髓、肠隐窝、表皮）可能由具有短且明确的分裂潜能的细胞组成。在这个模型中，这些细胞群的细胞被认为存在于一个有序的层次结构中，该层次结构为整个生物体寿命期间的细胞分裂建立了特定的顺序。所有层次水平上分裂潜能的耗尽导致细胞群功能丧失，并为物种寿命设定了内在限制。定义了细胞增殖的特定层次结构，这允许计算细胞群耗尽的时间，并最终计算生物体死亡的时间。该模型允许生物体中存在少量（n）关键细胞群，并将生物体死亡定义为这些细胞群中的任何一个无法产生细胞。该模型与所有与细胞和生物体衰老相关的主要观察结果一致。特别是，它将不同物种观察到的群体倍增极限（PDL）与其平均寿命联系起来；它解释了 PDL 作为供体年龄的函数的缓慢下降；它为无病群体建立了一个热力学稳定的最大寿命；并且它可以解释为什么组织移植比供体或宿主活得更长。
