Exogenous ketones target geroscience pathways and ameliorate geriatric syndromes - 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.
