CELL-MUTATIONAL TEST OF THE ERROR THEORY OF AGING

衰老错误理论的细胞突变测试

• 批准号: 3118129
• 负责人: AMIRAM RONEN
• 金额: $ 2.48万
• 依托单位: HEBREW UNIVERSITY OF JERUSALEM
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 1989-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3118129
• 关键词: Werner's syndrome; aging; autoradiography; cell age; cell population study; diphtheria toxin; fibroblasts; genetic disorder; human tissue; premature aging; tissue /cell culture

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.

拟议的研究旨在严格测试预测 根据奥格尔的错误灾难假说，细胞积累 突变作为年龄的指数函数。 这 白喉毒素抗性放射自显影测定 (48) 用于测量培养人类的突变频率 二倍体成纤维细胞。 细胞将来自正常供体和 异常的衰老相关综合征（早衰症、维尔纳综合征、 可卡因综合征和共济失调毛细血管扩张）。 这 放射自显影测定检测毒素抗性突变细胞 独立于其分裂或合成 DNA 的能力 （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体 人群从第一阶段进展到第三阶段 他们的生活。 通过使用放射自显影测定，将有可能 测量相对明确定义的突变频率 遗传系统不仅存在于活跃生长的文化中， 处于增殖末期的文化 生命，而且在所有细胞增殖都已达到的文化中 一个结束。 正是在这些阶段，积累了 奥格尔的理论预测错误是最戏剧性的。