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

饮食限制，GH/IGF-I

• 批准号: 8240033
• 负责人: VALTER D. LONGO
• 金额: $ 171.27万
• 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/8240033
• 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）：我们建议将来自洛杉矶不同学科，系和大学的实验室汇集在一起​​，以研究将饮食限制和饥饿与细胞保护和衰老联系起来的分子机制。这些研究将有助于鉴定药物和干预措施以治疗，并防止多种衰老疾病。该计划项目由3个主要项目，一个动物和生物统计学核心和一个行政核心组成。共同的目标是：a）确定可以保护正常细胞和器官的饮食干预措施和分子途径，以免受内源性和外源性毒素的侵害，重点是依赖年龄依赖性的氧化DNA，蛋白质损伤和寿命，b）了解细胞和有机体的潜在机制，并将重点放在凝聚力，氧化力依赖性因素依赖性，氧气依赖性（Er），氧化于氧化，ER）（ER）依赖性（ER）。假设是通过饥饿，遗传操纵和药物调节抗老化途径可以导致对正常和癌细胞对毒素的差异保护并延长寿命。 PI汇集了最佳的专业知识组合，从遗传学和分子生物学的衰老和压力抗性的调节的遗传学和分子生物学以及关注IGF-I，IGFBP及其信号途径的关注，以及对衰减和疾病的型号与较大的生物学相关的阶段和较大的阶段相关的阶段和挑战性挑战性和挑战性较大的型号。每个PI的独特背景以及它们之间的紧密合作已经产生，并将继续产生新颖的想法，以解决增长因素，抗压力，衰老和疾病之间非常复杂的联系。每个PI贡献的模型系统，转基因细胞和小鼠，试剂和技术专长无疑都以独立研究无法实现的方式加速了研究进度。