Regulation of aging by germline stem cells in C. elegans

描述(申请人提供)：线虫中的生殖系干细胞； 也就是说，产生精子和卵母细胞的细胞会影响衰老。 进程。杀死生殖系前体可延长约60%的寿命。 这种寿命的延长不仅仅是因为无菌，因为杀死 整个生殖系统的前体(生殖系以及 体细胞性腺)对寿命没有影响。为了进行生殖线消融 延长寿命，DAF-16蛋白，一种叉头家族转录因子， 是必需的。因此，延长寿命需要改变转录。在……里面 此外，这些动物还需要一种功能性的DAF-12类固醇激素 受体同系物。因此，生殖系干细胞可能在 通过调节小行星荷尔蒙而衰老。通过使用突变来消除 特定的生殖细胞亚群(精子、卵母细胞、生殖系干细胞)，我们有 发现生殖系干细胞调节成年动物的衰老。如果 生殖系干细胞在成年被迫退出有丝分裂并进入减数分裂 动物，寿命延长了。在这项研究中，我们将调查 生殖系干细胞影响衰老过程的机制。我们会 确定DAF-16和DAF-12活动的作用部位，我们将 确定这些基因的下游靶点，从而延长寿命 微阵列分析。此外，我们还将筛选起作用的新基因 在这个途径中，我们将开始确定它们的分子活性和 他们的行动时间和地点。这些研究可以定义 不仅在线虫中调节衰老，而且在高等生物体中也调节衰老，包括 人类。使用这些信息，可能会提高 并延缓与年龄有关的疾病的发病，如癌症和 糖尿病。此外，我们的发现可能会深入了解 干细胞可以影响脊椎动物的内分泌信号。

DESCRIPTION (provided by applicant): In C. elegans, the germline stem cells; that is, the cells that give rise to sperm and oocytes, influence the aging process. Killing the germline precursors extends lifespan approximately 60%. This lifespan extension is not simply due to sterility, because killing the precursors of the entire reproductive system (the germline as well as the somatic gonad) has no effect on lifespan. In order for germline-ablation to extend lifespan, the DAF-16 protein, a forkhead-family transcription factor, is required. Thus, lifespan extension requires changes in transcription. In addition, the animals also require a functional DAF-12 steroid hormone receptor homologue. Thus, germline stem cells may exert their effects on aging by regulating asteroid hormone. By using mutations to eliminate specific subsets of germ cells (sperm, oocytes, germline stem cells), we have found that the germline stem cells regulate aging in adult animals. If the germline stem cells are forced to exit mitosis and enter meiosis in adult animals, lifespan is extended. In this study, we will investigate the mechanism by which germline stem cells influence the aging process. We will determine the sites of action of DAF-16 and DAF-12 activity, and we will identify downstream targets of these genes that extend lifespan using microarray analysis. In addition, we will screen for new genes that function in this pathway, and we will begin to determine their molecular activities and their times and sites of action. These studies could define pathways that regulate aging not only in C. elegans, but also in higher organisms, including humans. Using this information, it may be possible to improve the quality of old age, and to delay the onset of age-related diseases, such as cancer and diabetes. In addition, our findings may yield insights into the ways that stem cells can influence endocrine signaling in vertebrates.