Regulation of germline stem cell aging by insulin S.ignaling

描述（由申请人提供）：在许多生物体（包括人类）中，不能随年龄保持干细胞与组织变性和对组织损伤的易感性增加等疾病有关。这项提案利用C. elegans germline生殖系as a model模型.利用C.秀丽隐杆线虫及其生殖系揭示了衰老和干细胞生物学的保守机制，因此，该提议结合了用于衰老研究的成熟遗传模型和定义明确、可获得的干细胞系统，提供了一个独特的机会来剖析衰老对干细胞动力学的影响。我们将确定干细胞耗竭的细胞机制及其通过胰岛素/IGF信号通路的预防。我们还将确定胰岛素/IGF信号通路的这种特定抗衰老作用的具体组织要求。这些试点研究将为今后的工作奠定基础。 公共卫生相关性：老龄化影响生殖。该应用是根据我们的发现，即C. elegans种系以依赖于保守的胰岛素/IGF信号传导途径的方式随着年龄的增长而耗尽。我们的研究将可能有益于人类健康，因为衰老和干细胞动力学的细胞和分子机制在进化上是保守的。

DESCRIPTION (provided by applicant): Failure to maintain stem cells with age is associated with conditions such as tissue degeneration and increased susceptibility to tissue damage in many organisms, including humans. This proposal addresses how aging affects stem cells using the C. elegans germ line as a model. Studies using C. elegans and its germ line have revealed conserved mechanisms of aging and stem cell biology, therefore this proposal combines a well-established genetic model for aging studies and a well- defined, accessible stem cell system, providing a unique opportunity to dissect the effects of aging on stem cell dynamics. We will determine the cellular mechanisms underlying stem cell depletion and its prevention by the insulin/IGF-signaling pathway. We will also determine the specific tissue requirements for this particular anti-aging effect of the insulin/IGF-signaling pathway. These pilo studies will lay the groundwork for future work. PUBLIC HEALTH RELEVANCE: Aging impacts reproduction. This application follows from our discovery that the proliferative stem cell population of the C. elegans germ line is depleted with age in a manner dependent on the conserved insulin/IGF signaling pathway. Our studies will likely benefit human health since the cellular and molecular mechanisms underlying aging and stem cell dynamics are evolutionarily conserved.