CELL-MUTATIONAL TEST OF THE ERROR THEORY OF AGING

这项拟议的研究旨在对这一预测进行批判性检验。 根据奥尔格尔的错误灾难假说，细胞积累 突变是年龄的指数函数。这个 白喉毒素抗性放射自显影检测(48)将是 用来测量培养的人的突变频率 二倍体成纤维细胞。细胞将来自正常捐赠者和来自 与衰老相关的异常综合征(早衰症、沃纳综合征、 Cocayne综合征和共济失调毛细血管扩张症)。这个 放射自显影检测耐毒素突变细胞 与它们分裂或合成DNA的能力无关 (唯一的要求是细胞能够合成 蛋白质)。因此，它可以同样准确地检测突变 从第一阶段到第三阶段的人口数量 他们的生活。通过使用放射自显影分析，这将是可能的 为了测量一个相对定义明确的 遗传系统不仅存在于活跃生长的文化中，也存在于 处于其增殖的末期的文化 生命，但也是在所有细胞增殖都已经达到 结束了。正是在这些阶段，积累了 根据奥尔格尔的理论，错误将是最严重的。

The proposed research is aimed at critically testing the prediction from Orgel's error catastrophe hypothesis, that cells accumulate mutations as exponential function of their age. The autoradiographic assay for diptheria toxin-resistance (48) will be used to measure the frequence of mutation in cultured human diploid fibroblasts. Cells will come from normal donors and from abnormal aging-related syndromes (progeria, Werner's syndrome, Cocayne's syndrome and ataxia telangiectasia). The autoradiographic assay detects toxin-resistant mutant cells independently of their capacity to divide or to synthesize DNA (the only requirement being that cells are capable of synthesizing proteins). It can thus detect mutants with equal accuracy in populations as they progress from phase I through phase III of their life. By using the autoradiographic assay, it will be possible to measure the frequency of mutation in a relatively well defined genetic system not only in actively growing cultures, or in cultures which are at the terminal stages of their proliferative life, but also in cultures where all cell proliferation has come to an end. It is precisely at these stages where the accumulation of errors is predicted by Orgel's theory to be most dramatic.