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

描述（由申请人提供）：我们建议将来自洛杉矶不同学科、部门和大学的实验室聚集在一起，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。该计划项目包括3个主要项目，动物和生物统计学核心和行政核心。共同目标是：a）确定可以保护正常细胞和器官免受内源性和外源性毒素的影响的饮食干预和分子途径，重点关注年龄依赖性氧化DNA和蛋白质损伤以及寿命，B）理解细胞和生物体衰老的潜在机制，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）测试以下假设：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和癌细胞对毒素的不同保护，并延长寿命。PI汇集了专业知识的最佳组合，范围从遗传学和饥饿依赖性调节衰老和抗应激的分子生物学，重点是IGF-I，IGFBPs及其信号传导途径，到内质网应激反应系统的知识及其与衰老和疾病的联系，以及与衰老生物学相关的高度挑战性程序和大规模动物研究的经验。每个PI的独特背景和他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，抗压力，衰老和疾病之间非常复杂的联系。每个PI贡献的各种模型系统、转基因细胞和小鼠、试剂和技术专业知识无疑正在以独立研究无法实现的方式加速研究进展。 公共卫生相关性： 对重大疾病的现代研究方法主要集中在诊断后的治疗上。在这里，我们建议汇集来自不同学科，部门，和大学在洛杉矶地区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的独特背景已经产生并将继续产生新的想法和策略，以解决非常复杂的联系，衰老和疾病。 审查可持续发展项目的各个组成部分 核心A：行政核心;瓦尔特博士，D。LONGO，核心负责人（CL） 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。核心A的目标是：1。一般行政管理，包括项目之间的互动管理，与NIA/NIH的沟通，财政和会计服务，以及建立一个网站，密码共享数据和手稿。2.促进会议和共享，包括组织所有研究者的双周会议，与内部和外部咨询委员会的会议，以及协调不同项目之间的材料，用品，细胞和动物的共享。3.进度，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，以确保维持计划项目的目标。4.交流，包括让大学生、研究人员和教职员工了解预防和治疗疾病的新的老龄化研究战略，提高他们对老年医学的兴趣，与行政部门合作组织与预防和治疗疾病的老年医学方法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关于作为本PO 1的一部分进行的研究的进展。 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，并为整个计划提供监督和战略规划。

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.