The Cell Biology of Cancer and Aging

描述（由申请人提供）：该项目的广泛，长期目标是提供有关癌症和衰老的细胞生物学知识的坚实基础。该项目的第一部分涉及对培养中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关系的批判性分析。这项分析将包括端粒酶和端粒在限制培养中人类细胞寿命方面的作用，以及这些组分与生物体中细胞存活、分化和癌症的相关性。它将包括对拟用于人类治疗的人工永生化细胞的安全性的考虑。该项目的第二部分将比较培养物、生物体和癌症中细胞的遗传稳定性。组织结构在维持机体内稳态中的作用将被广泛地综述。这种自上而下的控制随着年龄的增长而减弱，将被认为是与衰老过程相关的各种慢性疾病的起源。该方法是使用密切，密集的阅读的主要历史和当代科学文献有关的主题。重点将放在整合每个领域的生物学基础上，通常假设，但只有表面上的理解，与最近的分子研究结果，以开发一个更全面的，在癌症和衰老的细胞变化的理论基础。 一些广泛的评论将发表在领先的科学期刊上，最终统一成一本专著。这些和相关主题的综合卷的融合是考虑。

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.