Exogenous ketones target geroscience pathways and ameliorate geriatric syndromes

NIA研究和创业发展沉浸奖（K 01）的申请描述了Brianna Stubbs博士的五年职业发展计划，她是加利福尼亚州诺瓦托巴克老龄化研究所的翻译科学家。Stubbs博士的长期职业目标是成为一名独立的临床研究人员和企业家，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。 本申请中概述的具体职业发展目标包括发展老年科学生物标志物研究方面的专业知识;老年人的临床工作，IND使药物开发研究和转化创业。斯塔布斯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。斯塔布斯博士的职业发展计划和研究计划包括与她的导师团队，正式课程和会议的个性化指导，并围绕沉浸在巴克业务发展部门，在老年人的学术临床试验和行业药物开发计划的经验。Stubbs博士将在其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，人体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生物科学家。 研究计划的总体目标是确定老年科学生物标志物，用于未来的酮基药物开发。酮是在禁食或剧烈运动期间从储存的脂肪中产生的，强有力的临床前数据表明，它们可以通过充当氧化燃料和信号代谢物来影响寿命和健康。该项目的中心假设是酮体调节老年综合征常见的老年科学途径，包括炎症、衰老和线粒体健康。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和前虚弱和虚弱老年人中炎症，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相关联。 该应用程序与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疗法。该研究计划的预期结果将推动基于酮的心力衰竭治疗的进展。如果成功，Stubbs博士的职业生涯将导致老年综合征的多种干预措施的发展，最终导致老年人更健康和独立。

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.