Dietary Restriction, GH/IGF-I & Mechanisms of Differential Cellular Protection

饮食限制，GH/IGF-I

• 批准号: 8429461
• 负责人: VALTER D. LONGO
• 金额: $ 159.03万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-15 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8429461
• 关键词: Accounting; Acute; Address; Advisory Committees; Aging; Animals; Area; Biological Models; Biology of Aging; Biostatistics Core; Cells; Chronic; Collaborations; Communication; Complex; DNA; Data Analyses; Diagnosis; Dietary Intervention; Discipline; Disease; Ensure; Faculty; Feedback; Foundations; Genetic; Gerontology; Goals; Growth Factor; Insulin-Like Growth Factor I; Intervention; Knowledge; Laboratories; Link; Longevity; Los Angeles; Manuscripts; Molecular; Molecular Biology; Mus; Normal Cell; Organ; Pathway interactions; Pharmaceutical Preparations; Preparation; Prevention; Procedures; Proteins; Reading; Reagent; Reporting; Research; Research Personnel; Resistance; Services; Signal Pathway; Signal Transduction; Starvation; Strategic Planning; Stress; System; Technical Expertise; Technology; Testing; Toxin; Translating; United States National Institutes of Health; Universities; Work; age related; anti aging; base; biological adaptation to stress; cancer cell; data sharing; dietary restriction; endoplasmic reticulum stress; experience; genetic manipulation; genetically modified cells; interest; lectures; meetings; novel; prevent; programs; symposium; university student; web site

DESCRIPTION (provided by applicant): We propose to bring together laboratories from different disciplines, departments, and universities in Los Angeles to study the molecular mechanisms linking dietary restriction and starvation to cellular protection and aging. These studies will contribute to the identification of drugs and interventions to treat but also prevent multiple diseases of aging. The program project consists of 3 major projects, an Animal and Biostatistics Core and an Administrative Core. The common goals are to: a) identify dietary interventions and molecular pathways that can protect normal cells and organs against both endogenous and exogenous toxins with focus on age-dependent oxidative DNA and protein damage and life span, b) understand the underlying mechanisms of cellular and organismal aging with focus on starvation, growth factors-dependent signaling, oxidative and endoplasmic reticulum (ER) stress, c) test the hypothesis that the modulation of anti aging pathways by starvation, genetic manipulations and drugs can result in differential protection of normal and cancer cells against toxins and extend longevity. The PIs bring together an optimal combination of expertise ranging from those in the genetics and molecular biology of starvation-dependent modulation of aging and stress resistance with focus on IGF-I, IGFBPs, and their signaling pathways, to knowledge of endoplasmic reticulum stress response systems and their link to aging and diseases, to experience with highly challenging procedures and large scale animals studies related to the biology of aging. The unique background of each PI and the close collaborations between them has generated and will continue to generate novel ideas to address the very complex link between growth factors, stress resistance, aging, and diseases. The variety of model systems, genetically modified cells and mice, reagents, and technical expertise contributed by each PI is undoubtedly accelerating the research progress in a way that could not be achieved by independent studies.

描述（由申请人提供）：我们建议将洛杉矶不同学科、部门和大学的实验室聚集在一起，研究饮食限制和饥饿与细胞保护和衰老之间的分子机制。这些研究将有助于确定治疗和预防多种衰老疾病的药物和干预措施。该计划项目由 3 个主要项目组成：动物和生物统计核心项目和行政核心项目。共同目标是：a) 确定饮食干预措施和分子途径，以保护正常细胞和器官免受内源性和外源性毒素的侵害，重点关注年龄依赖性氧化 DNA 和蛋白质损伤和寿命，b) 了解细胞的潜在机制和生物衰老，重点关注饥饿、生长因子依赖性信号传导、氧化和内质网 (ER) 应激，c) 检验这样的假设：通过饥饿、基因操作和药物调节抗衰老途径可以导致正常细胞的差异保护和癌细胞对抗毒素并延长寿命。 PI 汇集了各种专业知识的最佳组合，从饥饿依赖性衰老和抗应激调节的遗传学和分子生物学（重点关注 IGF-I、IGFBP 及其信号通路）到内质网应激反应系统的知识及其与衰老和疾病的联系，体验与衰老生物学相关的极具挑战性的程序和大规模动物研究。每位 PI 的独特背景以及他们之间的密切合作已经并将继续产生新颖的想法，以解决生长因子、抗压性、衰老和疾病之间非常复杂的联系。每位PI贡献的各种模型系统、转基因细胞和小鼠、试剂和技术专长无疑正在以一种独立研究无法实现的方式加速研究进展。