The Cell Biology of Cancer and Aging

描述(由申请者提供)：该项目广泛的、长期的目标是提供关于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的长期复制之间的关系进行关键分析，特别是干细胞的复制。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，以及这些成分与细胞存活、分化和有机体中的癌症的相关性。它将包括对拟议使用人工永生化细胞进行人类治疗的安全性的考虑。该项目的第二部分将比较培养细胞、生物体细胞和癌症细胞的遗传稳定性。组织结构在维持生物体内稳态中的作用将被广泛回顾。这种自上而下的控制随着年龄的增长而减弱，这将被认为是与衰老过程相关的各种慢性病的根源。这种方法是对与主题相关的原始历史文献和当代科学文献进行仔细、深入的阅读。重点将放在将每个领域的生物学基础(通常是假设的，但只是表面上理解的)与最近的分子发现相结合，以开发癌症和衰老中细胞变化的更全面的理论基础。几篇广泛的评论将在领先的科学期刊上发表，随后最终统一成一本专著。考虑将这些主题和相关主题合并成一本全面的卷。

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.