Cellular aging--postreplicative cells. A review (Part II).
Cellular aging--postreplicative cells. A review (Part II).
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细胞衰老——复制后细胞。
DOI：
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发表时间：
1977
期刊：
影响因子：
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通讯作者：
G. M. Martin
中科院分区：
文献类型：
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作者：
G. M. Martin
人们普遍认为，限制哺乳动物寿命的关键改变是那些不再能够进行有丝分裂复制的细胞，因此不再能够通过增加后代数量来补偿细胞数量、结构或功能的缺陷。虽然这是直观的吸引力，我知道没有令人信服的证据表明克隆衰老的现象，在本评论的第一部分中讨论，不应该变成至少与衰老的病理生物学同等重要。显然，在这两个问题上都需要进行更多的研究。由于在这篇比较简短的综述中，显然不可能批判性地讨论所有甚至大多数增殖后细胞类型中与年龄相关的变化的主要观察结果，我选择将自己限制在三种细胞类型中（除了小的偏离）：a）卵母细胞，B）神经元，和c）心肌细胞。卵母细胞是特别感兴趣的，因为最终的生物测定功能缺陷的可用性，即年龄对其合子后代的活力和表型的影响。这种细胞类型的老化也是重要的进化结果，因为在一些哺乳动物物种中，包括人和至少一种近交系小鼠（CBA），卵母细胞在个体体细胞死亡之前很久就耗尽了，因此是限制种群繁殖能力的因素之一。最后，考虑到卵母细胞在生长、发育和衰老过程中的巨大损耗，有一种重要的可能性是，一个重要的遗传选择过程可能在起作用，该过程涉及一种或多种质量控制和非常成功的修复机制;其中一些可能是高度专业化的，（如各种形式的DNA修复）可以与那些发生在体细胞。在这方面，非常有趣的是，在共济失调毛细血管扩张症中，现在认为是由α射线反应性核酸内切酶的遗传缺陷引起的，2可能存在深刻的和预先的遗传缺陷。
THERE IS WIDESPREAD BELIEF that the alterations which are crucial in limiting the life-spans of mammals are those which involve cells no longer capable of mitotic replication and hence no longer capable of compensating-via increased numbers of progeny-for deficiencies in cell numbers, structure, or function. While this is intuitivelv appealing, I know of no compelling evidence that the phenomenon of clonal senescence, discussed in Part I of this review, should not turn out to be of at least equivalent importance to the pathobiology of aging. Clearly, a great deal more research is required on both subjects. Since it is manifestly impossible, in this comparativelv brief review, to critically discuss the major observations on age-associated changes in all or even most postreplicative cell types, I have chosen to confine mvself (except for minor digressions) to three such cell types: a) oocytes, b) neurons, and c) myocardial cells. Oocytes are of special interest because of the availability of the ultimate bioassay for functional defects-namely, the effects of age on the viabilitv and phenotype of their zygotic progeny. Aging of this cell type is also of great evolutionary consequence, since in some mammalian species, including man and at least one inbred strain of mice (CBA),1 oocvtes are depleted long before the somatic death of the individual and therefore are among those factors which limit the reproductive performance of the population. Finally, there is the important possibilitv, in view of the enormous attrition of oocytes during growth, development, and senescence, that a vital genetic selectional process mav be at work that involves one or a whole variety of quality control and variably successful repair mechanisms; some of these may be highly specialized and some (such as various modalities of DNA repair) may be comparable to those which take place in somatic cells. In this connection, it is of great interest that in ataxia telangiectasia, now considered to result from a hereditarv defect in a a-ray-responsive endonuclease,2 there could be a profound and pre-