The Cell Biology of Cancer and Aging

描述（由申请人提供）：该项目的长期目标是为癌症和衰老的细胞生物学知识提供坚实的基础。该项目的第一部分包括对培养细胞的有限寿命与生物体中细胞（特别是干细胞）的长期复制之间的关系进行批判性分析。这一分析将包括端粒酶和端粒在限制培养的人类细胞寿命中的作用，以及这些成分与细胞存活、分化和有机体中癌症的相关性。它将包括考虑拟用人工永生化细胞治疗人类的安全性。该项目的第二部分将比较培养细胞、生物体和癌症细胞的遗传稳定性。组织结构在维持生物体内平衡中的作用将被广泛地回顾。这种自上而下的控制随着年龄的增长而减弱，将在与衰老过程相关的各种慢性疾病的起源中得到考虑。方法是使用密切的，精读的主要历史和当代科学文献相关的主题。重点将放在整合每个领域的生物学基础，通常假设，但只是肤浅的理解，与最近的分子发现，以发展更全面的，癌症和衰老的细胞变化的理论基础。几篇广泛的评论将发表在主要的科学期刊上，最终将统一成一本专著。合并这些和相关的主题在一个全面的卷是考虑。

DESCRIPTION (provided by applicant):The broad, long-term objective of the project is to provide a solid foundation of knowledge about the cellular biology of cancer and aging. The first part of the project involves a critical analysis of the relationship between the limited lifespan of cells in culture and the long term replication of cells in the organism, particularly of the stem cells. This analysis will encompass the role of telomerase and telomeres in limiting the lifespan of human cells in culture and the relevance of these components to cell survival, differentiation and cancer in the organism. It will include consideration of the safety of the proposed use of artificially immortalized cells for therapy in humans. The second part of the project will compare the genetic stability of cells in culture, in the organism and in cancer. The role of tissue architecture in maintaining homeostasis in the organism will be extensively reviewed. The weakening of this top-down control with age will be considered in the origin of various chronic diseases associated with the aging process. The method is to use close, intensive reading of both the primary historical and the contemporary scientific literature relevant to the subjects. Emphasis will be placed on integrating the biological foundation of each field, often assumed but only superficially understood, with recent molecular findings to develop a more comprehensive, theoretical foundation of cellular change in cancer and aging. Several extensive reviews will be published m leading scientific journals to be followed eventually by unification into a monograph. Amalgamation of these and related subjects in a comprehensive volume is contemplated.