A new vertebrate model to study the role of growth factors IGF1 and IGF2 in sex dimorphism of longevity and aging.

女性比男性长寿，不同的年龄相关疾病困扰着女性和男性 不同的价格。我们对这些性别差异的基础缺乏了解会导致差异 在成功治疗与年龄相关的疾病方面，男性和女性之间存在差异。胰岛素和 胰岛素样信号通路(IIS)是已知的调节长寿的分子途径。的总目标是 拟议的研究计划是测试调节IIS途径的荷尔蒙是否有助于 长寿和衰老中的性别二形性。对其中一种荷尔蒙IGF2的研究已经完成 由于缺乏在成年时自然表达IGF2的动物模型。要克服 在这个屏障上，本研究将使用一种新颖的模型系统--棕色变态蜥蜴，它自然地 在成年期表达IGF2，类似于人类，回答关于IGF2的作用的问题 IGF2在衰老中的作用。这项提案有两个具体的目标，其中包括两个棕色的实验 变态实验室菌落和蜥蜴细胞培养系统。《特定目标1》使用纵向 在生物体水平上进行实验，以确定IGF1和IGF2在性行为中的各自作用 衰老与长寿的两面性。特定目标2使用细胞培养实验来测试 男性细胞环境是促进衰老的，如果IIS信号中的性别差异成为 随着年龄的增长而编程。这一贡献将是重大的，因为它将消除 我们对促生长轴在性别特异的衰老生物学中的作用的了解 开发和使用替代陆地脊椎动物模型和比较方法 与已建立的模型协同工作。此外，研究和实践的结合 这个项目的本科教育是为了提供广泛的实践研究。 每年为50名本科生研究人员提供与衰老生物学相关的经验。这个 拟议的研究和开发的方法论将开辟新的研究途径，目前 在IGF2和IIS的其他最高监管机构上，我们的标准模型系统是无法实现的 在自然衰老过程中发挥作用的途径。

Women live longer than men, and different age-related diseases afflict women and men at different rates. Our poor understanding of the basis of these sex-differences promote disparities between men and women in the success of treatments of age-related diseases. The Insulin and Insulin-like Signaling (IIS) molecular pathway is known to regulate longevity. The overall goal of the proposed research program is to test if hormones that regulate the IIS pathway contribute to sexual dimorphism in longevity and aging. Research on one of these hormones, IGF2, has been limited by the lack of an animal model that naturally expresses IGF2 in adulthood. To overcome this barrier, this research will use a novel model system, the brown anole lizard, which naturally expresses IGF2 through adulthood similarly to humans, to address questions on the role of IGF2 in aging. This proposal has two Specific Aims that include experiments both in a brown anole laboratory colony and in a lizard cell culture system. Specific Aim 1 uses a longitudinal experiment at the organismal level to define the respective roles of IGF1 and IGF2 in sexual dimorphism of aging and longevity. Specific Aim 2 uses cell culture experiments to test whether the male cellular environment is pro-aging, and if sex differences in IIS signaling become programmed with age. This contribution will be significant because it will remove a blind spot in our knowledge on the function of the somatotropic axis on the sex-specific biology of aging by developing and using an alternative terrestrial vertebrate model and comparative approaches that are synergistic with established models. Furthermore, the integration of research and undergraduate education with this project is designed to provide extensive hands-on research experience related to the biology of aging for 50+ undergraduate researchers annually. The proposed research and developed methodology will open new avenues of research, currently unattainable with our standard model systems, on IGF2 and other top regulators of the IIS pathway that play a role in the natural processes of aging.