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、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。 公共卫生相关性：主要疾病的现代研究方法主要集中于这些疾病诊断后的治疗。在这里，我们建议汇集洛杉矶地区不同学科、部门和大学的实验室，了解细胞保护和衰老的分子机制，并将其应用于药物和干预措施的鉴定，以预防和治疗衰老疾病。每个PI的背景已经并将继续产生新的想法和策略，以解决衰老与疾病之间非常复杂的联系。 计划项目各个组成部分的审查 核心A：行政核心；博士。 VALTER, D. LONGO，核心领导者 (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、财政和组织协调，促进互动、定期会议和技术共享，并为项目和核心提供监督和战略规划。整个程序。核心 A 的目标是： 1. 总务管理，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用于共享数据和手稿的密码网站。 2. 促进会议和共享，包括组织所有研究者每两周一次的会议、与内部和外部咨询委员会的会议，以及协调不同项目之间材料、用品、细胞和动物的共享。 3. 进展，包括分析各个组成部分产生的数据、阅读内部和外部咨询委员会的报告以及向每个核心和项目提供反馈，以确保维持计划项目的目标。 4. 交流，包括向大学生、研究人员和教师介绍基于衰老研究的新型预防和治疗疾病的策略，并提高他们对生物老年学的兴趣，与政府合作组织与基于生物老年学的预防和治疗方法相关的研讨会和公开讲座治疗疾病，建立一个网站来教育公众、研究人员和临床医生作为本 PO1 的一部分进行的研究进展。 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，并为该计划提供监督和战略规划，一个整体。