GENETIC AND MOLECULAR ANALYSIS OF AGING AND APOPTOSIS IN THE YEAST, SACCHAROMYCE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 细胞衰老和程序性细胞死亡（凋亡）是两个与人类疾病有关的细胞过程。例如，现在很清楚，两者都是有效的抗癌机制。逃避衰老或绕过细胞凋亡的细胞对致癌刺激的反应可能会发生恶性转化。有些人甚至把逃避程序性细胞死亡的能力称为“癌症的标志”。“重要的是，有充分的证据表明衰老和凋亡有助于许多化疗药物的抗肿瘤活性，并且使凋亡失效的突变可能导致多药耐药性。 芽殖酵母酿酒酵母已成为后生动物细胞复杂生理过程（包括衰老和凋亡性细胞死亡）的有用模型。这两个过程的分子机制似乎是保守的，遗传决定因素已被确定在酵母中与高等生物的直系同源物。 该研究计划概述了几种遗传策略，以确定酵母中这两个过程之间的分子联系。它将利用酵母系统相对于哺乳动物系统的主要优势作为衰老的模型系统  简单地说，酵母细胞更容易处理，因为它们会在几周内老化并达到衰老。 另一方面，哺乳动物细胞需要几个月才能衰老，而哺乳动物生物体需要几年甚至几十年才能衰老。考虑到不同物种的衰老和凋亡途径的显着保守性，这种分析利用了与酵母系统相关的遗传工具和易于研究的特点，应该会进一步深入了解包括人类在内的高等生物中的类似过程。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cellular aging and programmed cell death (apoptosis) are two cellular processes that have been implicated in human disease. For instance, it is now clear that both are potent anti-cancer mechanisms. Cells that either escape senescence or bypass apoptosis in response to oncogenic stimuli can undergo malignant transformation. Some have even called the ability to evade programmed cell death a "hallmark of cancer." Significantly, there is good evidence that senescence and apoptosis contribute to the anti-tumor activity of many chemotherapeutic drugs and that mutations that disable apoptosis can result in multi-drug resistance. The budding yeast Saccharomyces cerevisiae has served as a useful model for complex physiological processes of metazoan cells including aging and apoptotic cell death. Molecular mechanisms of both these processes appear to be conserved and genetic determinants have been identified in yeast with orthologues in higher organisms. This research program outlines several genetic strategies to identify molecular links between these two processes in yeast. It will exploit the primary advantage of the yeast system over its mammalian counterpart as a model system for aging  simply, yeast cells are easier to work with because they age and reach senescence within a matter of weeks. Mammalian cells, on the other hand, take months to undergo senescence, while mammalian organisms take years, if not decades, to age. Given the remarkable conservation of the aging and apoptotic pathways across diverse species, this analysis, which takes advantage of the genetic tools and ease of study associated with the yeast system, should lead to further insights into the analogous processes in higher organisms including human beings.