Exogenous ketones target geroscience pathways and ameliorate geriatric syndromes

外源酮针对老年科学途径并改善老年综合症

• 批准号: 10700161
• 负责人: Brianna Jane Stubbs
• 金额: $ 17.55万
• 依托单位: BUCK INSTITUTE FOR RESEARCH ON AGING
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10700161
• 关键词: Address; Affect; Aging; Animals; Aorta; Award; Biological Markers; Biology; Biopsy; Blood; Blood Vessels; Brain; Businesses; Caenorhabditis elegans; Cardiac; Chronic; Clinical; Clinical Research; Clinical Trials; Complement; Complex; Custodial Care; Data; Development; Development Plans; Disease; Drug Industry; EFRAC; Elderly; Elements; Endothelium; Entrepreneurship; Enzymes; Epigenetic Process; Esters; Family; Fasting; Fatty acid glycerol esters; Food; Frail Elderly; Functional disorder; Future; Geroscience; Goals; Health; Heart; Heart Diseases; Heart failure; Human; Immersion; Immune; Immune System Diseases; Individual; Industry; Inflammation; Inflammatory; Ingestion; Intervention; Intravenous; Ketone Bodies; Ketones; Knowledge; Left Ventricular Ejection Fraction; Lipids; Liver; Longevity; Mass Spectrum Analysis; Measures; Medical Care Costs; Mentors; Mentorship; Metabolic; Metabolism; Metformin; Methods; Mitochondria; Mitochondrial Proteins; Modeling; Molecular; Mus; Muscle; Myocardium; Obesity; Oral; Organ; Outcome Measure; Oxidative Stress; Pathway interactions; Patients; Phenotype; Physiological; Physiology; Plasma; Pre-Clinical Model; Production; Program Development; Proteins; Proteomics; Public Health; Rattus; Research; Research Institute; Research Personnel; Risk; Rodent; Rodent Model; Role; Scientist; Self Care; Signal Transduction; Skeletal Muscle; Strenuous Exercise; Syndrome; Testing; Therapeutic Uses; Tissues; Translating; Translational Research; United States National Institutes of Health; Wild Type Mouse; Work; age related; beta-Hydroxybutyrate; biomarker selection; career; career development; dietary; dietary restriction; drug development; experience; frailty; functional decline; functional outcomes; healthspan; improved; inhibitor; ketogenic diet; meetings; pre-clinical; preservation; randomized placebo controlled study; research and development; senescence; skills; societal costs; stressor; therapeutic target; translational potential; translational scientist; translational therapeutics; young adult

This application for the NIA Research and Entrepreneurial Development Immersion Award (K01) describes the five-year career development plan of Dr. Brianna Stubbs, a translational scientist at The Buck Institute for Research on Aging, Novato, CA. Dr. Stubbs’ long-term career goal is to be an independent clinical researcher and entrepreneur, and to build a track record of translating academic concepts into therapeutics targeting aging and age-related disease. The specific career development goals outlined in this application include developing expertise in the study of geroscience biomarkers; clinical work with older adults, IND enabling studies for drug development, and translational entrepreneurship. Dr. Stubbs will be supported by a team of academic, industry and business development mentors to accomplish these career development goals. The career development plan and research plan of Dr. Stubbs includes individualized mentorship with her mentorship team, formal coursework, and meetings, and is built around immersion in The Buck Business Development Department, experience in an academic clinical trial of older adults and in an industry drug development program. Dr. Stubbs will use biospecimens from these studies in her Research Plan. The plan will complement and extend Dr. Stubbs’ extensive experience in clinical research with young adults, human physiology, and development of ketone-based consumer food products, to equip her to be an independent entrepreneur-scientist. The overall objective of the research plan is to identify geroscience biomarkers for use in future ketone-based drug development. Ketones are produced from stored fat during fasting or strenuous exercise and strong preclinical data demonstrates that they can impact lifespan and healthspan by acting as an oxidative fuel and a signaling metabolite. The central hypothesis of this project is that ketone bodies modulate geroscience pathways common to geriatric syndromes including inflammation, senescence, and mitochondrial health. The specific aims of the research plan are to investigate the effects of exogenous ketones on the specific geroscience mechanisms of inflammation, senescence, and mitochondrial health in a rodent model of heart failure and in pre-frail and frail older adults, and to correlate changes in these pathways to functional outcomes. The application is relevant to NIH and NIA because Dr. Stubbs’ career goal is to leverage an understanding of the multifactorial pathways that regulate aging and longevity to provide translational therapies for the multifactorial geriatric syndromes. The anticipated results of the research plan will advance the progress of ketone-based treatments for heart failure. If successful, Dr. Stubbs’ career will result in the development of multiple interventions for geriatric syndromes, which ultimately leads to greater health and independence in older adults.

NIA研究和创业发展沉浸奖（K01）的申请描述了Brianna Stubbs博士的五年职业发展计划，Brianna Stubbs博士是加州诺瓦托巴克衰老研究所的转化科学家。Stubbs博士的长期职业目标是成为一名独立的临床研究员和企业家，并建立将学术概念转化为针对衰老和年龄相关疾病的治疗方法的记录。该申请概述了具体的职业发展目标，包括在老年科学生物标志物研究方面发展专业知识；老年人的临床工作，药物开发的IND使能研究，以及转化创业。Stubbs博士将得到一个由学术、行业和商业发展导师组成的团队的支持，以实现这些职业发展目标。Stubbs博士的职业发展计划和研究计划包括与她的指导团队进行个性化指导、正式课程和会议，并建立在Buck业务开发部门的沉浸感、老年人学术临床试验经验和行业药物开发计划的基础上。斯塔布斯博士将在她的研究计划中使用这些研究的生物标本。该计划将补充和扩展Stubbs博士在年轻人临床研究、人类生理学和基于酮的消费食品开发方面的丰富经验，使她成为一名独立的企业家和科学家。该研究计划的总体目标是确定用于未来酮类药物开发的老年科学生物标志物。酮是由禁食或剧烈运动时储存的脂肪产生的，强有力的临床前数据表明，它们可以作为一种氧化燃料和信号代谢产物，影响寿命和健康寿命。该项目的中心假设是酮体调节老年综合征（包括炎症、衰老和线粒体健康）常见的老年科学途径。该研究计划的具体目的是研究外源性酮对心力衰竭啮齿动物模型、体弱和体弱老年人的炎症、衰老和线粒体健康的特定老年科学机制的影响，并将这些途径的变化与功能结果联系起来。该申请与NIH和NIA相关，因为Stubbs博士的职业目标是利用对调节衰老和长寿的多因素途径的理解，为多因素老年综合征提供转化治疗。该研究计划的预期结果将推动以酮为基础的心力衰竭治疗的进展。如果成功，斯塔布斯博士的职业生涯将导致针对老年综合症的多种干预措施的发展，最终使老年人更加健康和独立。