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

饮食限制，GH/IGF-I

• 批准号: 8018805
• 负责人: VALTER D. LONGO
• 金额: $ 170.61万
• 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/8018805
• 关键词: Dietary; Restriction; GH; IGF; Mechanisms

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. PUBLIC HEALTH RELEVANCE: Modern research approaches on the major diseases focus primarily on the treatment of these diseases after they are diagnosed. Here, we propose to bring together laljoratories from different disciplines, departments, and universities in the Los Angeles area to understand the molecular mechanisms of cellular protection and aging and apply them to the identifications of drugs and interventions to prevent and treat diseases of aging The unique background of each of the PIs has generated and will continue to generate novel ideas and strategies to address the very complex link between aging and diseases. REVIEW OF INDIVUAL COMPONENTS OF THE PROGRAM PROJECT CORE A: ADMINISTRATIVE CORE; DR. VALTER, D. LONGO, CORE LEADER (CL) DESCRIPTION (provided by applicant): The overall goal of the administrative core is to provide scientific, fiscal, and organizational coordination of all the activities of the projects and cores, facilitate interactions, regular meetings and technology-sharing and provide oversight and strategic planning for the program as a whole. The aims of Core A are: 1. General Administration including the management of interactions between the projects, communication with the NlA/NIH, fiscal and accounting services and the set up of a website with password for sharing data and manuscripts In preparation. 2. Facilitate Meetings and Sharing, including organizing biweekly meetings of all investigators, meetings with the internal and external advisory committees, and coordinating the sharing of materials, supplies, cells, and animals between the different projects. 3. Progress, including analysis of the data produced by the various components, reading of reports by the Internal and External Advisory Committees, and providing feedback to each Core and Project to ensure that the goals of the program project are maintained. 4. Communication, including exposing university students, researchers and faculty to novel aging research-based strategies to prevent and treat diseases and enhance their interest in biogerontology, working with the administration to organize symposia and public lectures related to biogerontology-based approaches to prevent and treat diseases, setting up a web site to educate the public, researchers and clinicians about the progress of the research performed as part ofthis PO1. PUBLIC HEALTH RELEVANCE: The overall goal of the administrative core is to provide scientific, fiscal, and organizational coordination of all the activities of the projects and cores, facilitate interactions, regular meetings and technology-sharing and provide oversight and strategic planning for the program as a whole.

描述(由申请人提供)：我们建议将洛杉矶不同学科、系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多种衰老疾病的药物和干预措施。该方案项目由三个主要项目组成，一个是动物和生物统计核心，另一个是行政核心。这些研究的共同目标是：a)确定能够保护正常细胞和器官免受内源性和外源性毒素伤害的饮食干预措施和分子途径，重点关注依赖年龄的氧化DNA和蛋白质损伤及寿命；b)了解细胞和组织衰老的潜在机制，重点关注饥饿、生长因子依赖的信号转导、氧化和内质网应激；c)测试以下假设：饥饿、基因操作和药物对抗衰老途径的调节可导致正常细胞和癌细胞免受毒素的不同保护，从而延长寿命。PI集合了各种专业知识的最佳组合，包括依赖饥饿调节衰老和应激抗性的遗传学和分子生物学方面的专业知识，重点是IGF-I、IGFBPs及其信号通路，以及内质网应激反应系统及其与衰老和疾病的联系的知识，以体验与衰老生物学相关的高挑战性程序和大规模动物研究。每个PI的独特背景以及它们之间的密切合作已经产生并将继续产生新的想法，以解决生长因子、抗压能力、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、试剂和技术专长的多样性，无疑正在以独立研究无法实现的方式加快研究进展。 公共卫生相关性：对重大疾病的现代研究方法主要集中在这些疾病被诊断后的治疗上。在这里，我们建议将来自洛杉矶地区不同学科、系和大学的研究人员聚集在一起，以了解细胞保护和衰老的分子机制，并将它们应用于药物和干预措施的识别，以预防和治疗衰老疾病。每个PI的独特背景已经产生并将继续产生新的想法和战略，以解决衰老和疾病之间非常复杂的联系。 对计划项目的各个组成部分进行评审 核心A：行政核心；Valter博士，D.Longo，核心领导(CL) 描述(由申请人提供)：行政核心的总体目标是为项目和核心的所有活动提供科学、财政和组织上的协调，促进互动、定期会议和技术共享，并为整个计划提供监督和战略规划。核心A的目标是：1.一般行政管理，包括管理项目之间的互动、与NLA/NIH的沟通、财务和会计服务，以及建立一个网站，以便共享数据和准备中的手稿。2.促进会议和共享，包括组织所有调查人员每两周举行一次会议，与内部和外部咨询委员会举行会议，并协调不同项目之间共享材料、用品、细胞和动物。3.进展情况，包括分析各组成部分产生的数据，阅读内部和外部咨询委员会的报告，并向每个核心和项目提供反馈，以确保维持方案项目的目标。4.交流，包括让大学生、研究人员和教职员工接触新的以研究为基础的新战略，以预防和治疗疾病，并提高他们对生物老年学的兴趣，与行政部门合作，组织与以生物老年学为基础的方法预防和治疗疾病有关的研讨会和公开讲座，建立一个网站，教育公众、研究人员和临床医生了解作为本次宣传活动的一部分开展的研究的进展情况。 公共卫生相关性：行政核心的总体目标是为项目和核心的所有活动提供科学、财政和组织协调，促进互动、定期会议和技术共享，并为整个计划提供监督和战略规划。