Tissue-specific mitochondrial turnover with aging and energy restriction

组织特异性线粒体周转与衰老和能量限制

基本信息

批准号：
8230616
负责人：
Benjamin Francis Miller
金额：
$ 12.24万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-03-15 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8230616
关键词：
Acute Address Adult Age Aging Anabolism Biogenesis Colorado Deterioration Diet Dose Energy Metabolism Floods Funding Genetic Transcription Goals Heart Hour Instruction Isotopes Kidney Laboratories Laboratory Animals Laboratory Research Learning Leucine Liver Location Measurement Measures Mediating Mediator of activation protein Mentors Mentorship Messenger RNA Methodology Methods Michigan Mitochondria Mitochondrial Proteins Nutrient Pathway interactions Peroxisome Proliferator-Activated Receptors Process Protein Biosynthesis Rattus Research Research Design Research Personnel Role Signal Transduction Skeletal Muscle Techniques Tissue-Specific Gene Expression Tissues Tracer Training Translation Initiation Translations Universities age effect age related career experience feeding functional decline healthy aging in vivo mTOR protein protein degradation protein metabolism response skills stable isotope theories transcription factor translational approach

项目摘要

DESCRIPTION (provided by applicant): The candidate is a new investigator at Colorado State University (CSU). The candidate's long-term goal is to obtain independent funding to develop a research laboratory that uses an integrative and translational approach to investigate the interaction of energy and protein metabolism and their roles in the healthy aging of skeletal muscle. The immediate career goal is to obtain a protected period of research to develop skills for the assessment of potential tissue-specific mitochondrial turnover to changes in energy and with aging. Specifically, the proposed project addresses the protein turnover and mitochondrial theories of aging, and challenges the paradigm that protein turnover increases during periods of energy restriction (ER). The project will examine short and long- term changes in mitochondria turnover by redundant measurements to complete a comprehensive assessment of turnover. It is proposed that changes in mitochondria turnover will be mediated at the step of translation, since translation is an energetically expensive process. The mTOR and PGC-lot pathways, as well as AMPK activation will be explored as mediators of transcription and translation. The current proposal exploits the applicant's experience with stable isotopic tracers although new methods will be learned in the laboratory of Dr. Marc Hellerstein (UC-Berkeley, key consultant). Significant training aspects will be directed by Dr. Greg Cartee (University of Michigan, co-mentor) and Dr. Michael Pagliassotti (CSU, co- mentor) with instruction on the use of laboratory animals, ER methodology, tissue isolation techniques, and studies of cellular signaling. Study design, oversight and professional mentorship in aging research will be provided by Dr. Manfred Diehl (CSU, Director of the Center on Aging, co-mentor). RELEVANCE: Mitochondria deterioration has been proposed as causative to age-related decline in function. The current proposal seeks to understand how acute feeding, energy status (energy restricted (ER) or adequately fed), and tissue location effect age-induced changes in mitochondria turnover. It is hoped that the understanding of these processes will aid in safe and effective strategies for successful aging.

描述（由申请人提供）：候选人是科罗拉多州立大学（CSU）的新调查员。候选人的长期目标是获得独立的资金来开发研究实验室，该研究实验室使用综合和翻译方法来研究能量和蛋白质代谢的相互作用及其在骨骼肌健康衰老中的作用。直接的职业目标是获得一个受保护的研究时期，以开发技能，以评估潜在的组织特异性线粒体周转率，以使能量变化和衰老变化。具体而言，拟议的项目解决了衰老的蛋白质周转和线粒体理论，并挑战了蛋白质更新在能量限制期（ER）期间增加的范式。该项目将通过冗余测量结果来检查线粒体周转的短期和长期变化，以完成对营业额的全面评估。有人提出，由于翻译是一个昂贵的过程，线粒体周转的变化将在翻译步骤中进行介导。 MTOR和PGC-LOT途径以及AMPK激活将作为转录和翻译的介体探索。当前的提案利用了申请人的稳定同位素示踪剂的经验，尽管将在Marc Hellerstein博士（主要顾问UC-Berkeley）的实验室中学习新方法。重要的培训方面将由密歇根大学的Greg Cartee博士和Michael Pagliassotti博士（CSU，CO-CONOR）指导，并提供有关实验动物的使用，ER方法，组织隔离技术和细胞信号研究的指导。曼弗雷德·迪尔（Manfred Diehl）博士将提供研究设计，监督和专业指导，该研究将由曼弗雷德·迪尔（Manfred Diehl）博士（CSU，衰老中心，联合会员）提供。相关性：已提出线粒体恶化是与年龄相关的功能下降的原因。当前的提案旨在了解急性喂养，能量状态（能量限制（ER）或充分喂养）以及组织位置效应年龄诱导的线粒体转换变化。希望对这些过程的理解将有助于实现成功衰老的安全有效策略。