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

一种新的脊椎动物模型，用于研究生长因子 IGF1 和 IGF2 在长寿和衰老的性别二态性中的作用。

• 批准号: 9813428
• 负责人: Tonia S Schwartz
• 金额: $ 44.83万
• 依托单位: AUBURN UNIVERSITY AT AUBURN
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9813428
• 关键词: Address; Adult; Age; Aging; Alzheimer' s Disease; Animal Model; Animals; Binding; Biological; Biological Markers; Biological Models; Biology; Biology of Aging; Cell Aging; Cell Culture System; Cell Culture Techniques; Cell Line; Cells; Characteristics; Comparative Biology; Development; Disease; Environment; Exposure to; Female; Gender; Goals; Gonadal Steroid Hormones; Growth Factor; Hormonal; Hormones; Human; IGF1 gene; IGF2 gene; Insulin; Knowledge; Laboratories; Length; Life; Link; Liver; Lizards; Longevity; Malignant Neoplasms; Methodology; Modeling; Molecular; Mus; Organ; Organism; Pathway interactions; Pattern; Play; Population; Process; Rattus; Regulation; Research; Research Personnel; Retinal blind spot; Role; Sex Chromosomes; Sex Differences; Signal Pathway; Signal Transduction; Signaling Molecule; Societies; Somatotropin; Standard Model; Telomerase; Testing; Time; Translating; Woman; Work; age related; comparative; design; embryo tissue; experience; experimental study; hands on research; healthy aging; hormonal signals; human male; in vivo; mTOR Signaling Pathway; male; men; mortality; novel; programs; receptor; senescence; sex; sexual dimorphism; success; undergraduate education; undergraduate student

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.

女性比男性寿命长，不同的与年龄有关的疾病折磨着女性和男性， 不同的利率。我们对这些性别差异的基础缺乏理解， 男性和女性在成功治疗与年龄有关的疾病方面的差异。胰岛素和 胰岛素样信号传导（IIS）分子通路被认为是调节寿命的重要途径。的总目标 拟议的研究计划是测试调节IIS通路的激素是否有助于 寿命和衰老的两性异形。对其中一种激素IGF2的研究一直是 由于缺乏在成年期自然表达IGF2的动物模型而受到限制。克服 这个障碍，这项研究将使用一种新的模型系统，棕色变色蜥蜴， 表达IGF2通过成年类似于人类，以解决问题的作用， IGF2在衰老中的作用这项建议有两个具体目标，包括实验都在布朗 变色龙实验室菌落和蜥蜴细胞培养系统。具体目标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。 衰老和长寿的二态性。具体目标2使用细胞培养实验来测试是否 男性细胞环境是促衰老的，如果IIS信号传导的性别差异变得 随着年龄的增长。这一贡献将是重大的，因为它将消除一个盲点， 我们对促生长轴在性别特异性衰老生物学中的作用的认识， 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。此外，研究与 本科教育与这个项目的目的是提供广泛的实践研究 每年为50多名本科生研究人员提供与衰老生物学相关的经验。的 拟议的研究和开发的方法将开辟新的研究途径，目前， 这是我们的标准模型系统无法实现的，在IGF2和IIS的其他顶级监管机构上 在衰老的自然过程中发挥作用的途径。