Exogenous ketones target geroscience pathways and ameliorate geriatric syndromes

NIA研究和创业发展沉浸奖(K01)的申请书描述了加州诺瓦托巴克老龄化研究所的翻译科学家Brianna Stubbs博士的五年职业发展计划。斯塔布斯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，并在将学术概念转化为针对衰老和老年相关疾病的疗法方面建立了良好的记录。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记物研究方面的专业知识、老年人的临床工作、IND促进药物开发的研究以及翻译创业。斯塔布斯博士将得到学术、行业和商业发展导师团队的支持，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的个性化指导、正式的课程作业和会议，并以沉浸在Buck业务开发部、在老年人的学术临床试验和行业药物开发计划中的经验为基础。斯塔布斯博士将在她的研究计划中使用来自这些研究的生物标本。该计划将补充和扩展斯塔布斯博士在青年临床研究、人体生理学和以酮为基础的消费食品产品开发方面的丰富经验，使她成为一名独立的企业家兼科学家。该研究计划的总体目标是确定老年科学生物标记物，用于未来的酮类药物开发。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，它们可以作为氧化燃料和信号代谢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调查外源性酮对心力衰竭啮齿动物模型中炎症、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联系起来。这项申请与NIH和NIA相关，因为斯塔布斯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了解，为多因素老年综合征提供转化性治疗。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征的多种干预措施的开发，最终导致老年人更健康和更独立。

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.