Understanding how cellular metabolism interacts with the genes and pathways that regulate aging has led to many of the potential interventions now being investigated to promote healthspan. Exercise, fasting, and dietary restriction all work to promote health by activating specific cellular signaling pathways. Many of these signaling pathways involve ordinary cellular metabolites like acetyl-CoA and NAD, which have “secret” lives regulating enzymes and genes. The Newman lab focuses on an emerging signaling metabolite, the ketone body beta-hydroxybutyrate, and the roles it may have in responding to stressors and regulating healthspan.
Ketone bodies are the energy currency that allows the body’s cells to utilize fats for fuel. They are made normally in the liver from fats whenever carbohydrates are scarce, as when fasting or exercising. Ketone bodies are to fats what glucose is to carbohydrates. But beta-hydroxybutyrate has signaling activities as well, including regulating gene expression, modulating inflammation, and controlling metabolism by inhibiting enzymes, binding to proteins, and activating receptors. We have found that long-term exposure to ketone bodies using a ketogenic diet can extend the healthy lifespan of normal mice and, in particular, protect the aging brain. We seek a mechanistic understanding of how ketone bodies might work in an aging mammal to promote health, particularly in age-related memory decline and Alzheimer’s disease. Our goal is to develop targeted therapies that might enhance the resilience of older adults to diseases like Alzheimer’s and stresses like hospitalization.
Why it matters
The translation of geroscience into clinical practice has great potential to improve the lives of older adults. We already know that the best way to treat the complex medical problems of older adults is through the systematic, individualized geriatric medicine approach of comprehensive assessments and multidomain interventions. Interventions developed from geroscience usually act on multiple aging-related cellular pathways, like how the signaling activities of ketone bodies affect gene expression, inflammation, and metabolism. These interventions may hold great promise for treating complex geriatric syndromes like frailty, multimorbidity, and delirium that affect the health and independence of millions of older adults.
As a physician-scientist, working on interventions that act on multiple age-related cellular pathways is particularly rewarding. This may be the best way to address the complex geriatric syndromes that affect patients.
John Newman, MD, PhD
John Newman, MD, PhD, is an assistant professor at the Buck Institute for Research on Aging and in the Division of Geriatrics at University of California San Francisco (UCSF). His career goal is to translate our expanding understanding of aging biology to improve the care and help maintain the independence of older adults. His research at the Buck Institute studies the molecular details of how diet and fasting regulate the genes and pathways that in turn control aging, focusing on the ketone body beta-hydroxybutyrate and how its molecular signaling activities involving epigenetics and inflammation regulate aging and memory in mice.
Dr. Newman is also a geriatrician who cares for hospitalized older adults at UCSF and the San Francisco VA Medical Center, focusing on preserving mobility and preventing delirium. His undergraduate education was at Yale University, with a BS/MS in molecular biophysics and biochemistry that included studying growth factor signaling in the roundworm C. elegans. He completed an MD/PhD at the University of Washington, where his graduate work studies focused on the progeroid Cockayne syndrome with Dr. Alan Weiner. While at UW, he developed new bioinformatics tools for the analysis of patterns in gene expression data. He then completed a residency in internal medicine and fellowship training in geriatric medicine at UCSF. He is an National Institute on Aging Beeson Scholar.
Dr. Newman is a native of Long Island, New York, and a lifelong Mets fan. He has lived in San Francisco since 2008. He enjoys playing volleyball, watching baseball, exploring the natural beauty of the Bay Area, and having fun food experiences.
Thelma Y. García, PhD Lab Research and Administrative Manager
Dr. Thelma Garcia is the Newman Lab Research and Administrative Manager. Her prior research project involved maintaining a comprehensive database of ketone body metabolics. Thelma is primarily interested in glucose and insulin sensitivity, energy expenditure, lipid metabolism, and other potential metabolic effects of BHB and its structural analogs. She also enjoys expanding her mentoring skills and takes pride in training, supervising, and maintaining lab relationships while addressing inequities in the workplace for all historically marginalized groups. She proactively assesses the needs of the scientists and develops methods to enable the efficient functioning of the lab. Moreover, she coordinates with relevant departments and collaborating research institutions to ensure the needs of all scientists are met.
Dr. Garcia also serves as a hands-on research project manager. She assists scientists in planning and troubleshooting experiments to promote awareness and communication in the lab. As a safety lab officer, Thelma ensures full compliance, updates, and modifications of Biological User Authorizations (BUA, BSL-2), IACUC, IRB and any other permits for all projects. In the role of lab administrator, she manages capitals and budgets, resource requirements, and financial budget analysis, in addition to grant support.
She is an exemplary role model for the students of the Newman lab from starting her academic career as a first-generation college student herself and becoming an amazing and inspiring Latina leader for the team. She is also deeply invested in using best practices to increase student learning, reduce barriers and close the opportunity gap. She believes that everyone can be a capable STEM learner. Her passion and calling for equity in education through research in science is her engine. She attended Santa Rosa Junior College, Sonoma State University, and later completed doctoral studies in Chemistry at UC Davis. As a APHL-CDC/NCEH Environmental Health Fellow postdoctoral fellow, her focus was in human biochemistry/toxicology.
Thanh Blade Research Associate
Thanh Blade is a Research Associate in the Newman Lab at the Buck Institute. She obtained a Bachelor of Science in Biochemistry from Sonoma State University (Spring 2019). Her most recent research interest incorporates ketogenic diet metabolism. Her goal in life is to love what she does and to do what she loves. During her spare time, Thanh loves sharing food and walking or hiking with friends and family.
Asish Chaudhuri, PhD Staff Scientist
Research on Aging. His primary research interest is to understand how impaired protein homeostasis contributes to aging and age-related diseases like sarcopenia, Alzheimer’s, ALS, and diabetes. To address this question, he has developed various fluorescence-based technologies and applied to short-/ long-lived animals and disease mouse models (e.g., ALS, diabetic models) to test the working hypothesis that “accumulation of oxidized proteins as misfolded aggregates is the critical determinant for the onset and progression of aging and age-related diseases”. In November 2017, he and his colleagues got a patent on the discovery of the novel function of an FDA-approved drug, hydralazine, generally used for hypertension. They showed that hydralazine possesses anti-aging property. He received 13 grants as a Principal or as co-investigator and published 48 peer-reviewed papers including top peer-review journals like Nature Communication, PNAS, Aging cell, FASEB J., Methods in Enzymology, Methods in Molecular Biology, Biochemistry, Journal of Molecular Biology, Journal of Biological chemistry. He received Veteran Merit award. In 2020, Dr. Chaudhuri received the “Saaraswat Samman” award from GFL Business School, Kolkata, India.
In Newman’s laboratory, he will be focusing on four important aspects; (i) development of high throughput techniques for screening various beta-hydroxybutyrate derivatives and other molecules, (ii) development of disaggregation assay to screen molecules, and (iii) development of a strategy to find the target proteins for beta-hydroxybutyrate and its derivatives, and (iv) To understand the mechanism by which BHB controls protein quality in cells.
Dr. Asish Chaudhuri is from Kolkata (formerly called Calcutta), India. He lived 25 years in Texas, (mainly in San Antonio and Dallas) before he moved to California. He loves to play tennis, writing poetry, reading books, and hanging out with friends. He enjoys the food from different countries.
Brenda Eap USC/Buck Institute Biology of Aging PhD Program
Brenda completed her B.S. in Biochemistry with a minor in Forensic Science at California State University, Los Angeles in 2017. She studied how to delay senescence in Arabidopsis thaliana and was quickly intrigued by the aging process in plants. Brenda entered the USC-Buck Ph.D. Biology of Aging program in 2018 and joined the Newman Lab. Her Ph.D. work focuses on age-related changes in ketone body metabolism and how ketosis can help maintain energy homeostasis in aging. More specifically, she is interested in how a ketogenic diet and exogenous ketones can be useful therapies in older adults. She will also investigate how the ketone body, beta-hydroxybutyrate is an important metabolite and epigenetic regulator in aging.
During her spare time, she likes to bring friends together through social gatherings (with food!). Brenda also likes to travel and immerse herself in different cultures.
Wyatt Gray Laboratory Technician
Wyatt Gray started in the Newman Lab as an intern in 2018. In 2019, he was hired as a lab technician. He completed an associates degree from the Santa Rosa Junior College in biology and natural sciences. His work in the Newman lab involves rodent research and maintenance as well as ketogenic metabolism. In his spare time he enjoys adventuring in the outdoors, traveling, cooking delicious food, and admiring his cat, Rose.
Sidharth S. Madhavan USC/Buck Institute Biology of Aging PhD Program
Sid is a USC-Buck Ph.D. fellow in the Newman Lab. In 2019, he completed a B.S. in Clinical Neuroscience with honors at Virginia Tech. As an undergraduate, he researched structural and biochemical properties of tau proteins, specifically relating to clinical mutations affecting aggregation. As a Ph.D. fellow in the Newman Lab (2020), he will build on his background, investigating the propensity for small energetic metabolites to modulate proteostasis in Alzheimer’s disease.
When he isn’t at the bench, Sid loves being outdoors. He has hiked most of the Appalachian Trail in southwest Virginia and enjoys the accessibility to backcountry hiking out west. Sid also enjoys running, cooking new recipes, falling asleep in his hammock, and teaching himself bluegrass flatpicking.
Mitsunori Nomura, PhD Research Scientist
Dr. Mitsunori Nomura is a Research Scientist in the Newman lab. His project involves studying how the ketone body beta-hydroxybutyrate (BHB), which is made in the liver by the fatty acid oxidation (FAO) during fasting, ketogenic diet feeding, and exercise, affects the aging brain and age-related diseases. He will use ketone body compounds (BHB derivatives), diet interventions, and genetic modifications in both cells and rodent models to understand the mechanistic effects of ketone bodies on memory and other phenotypes in normal aging and Alzheimer’s disease models. In particular, Dr. Nomura’s research will focus on the role of BHB in the metabolic regulation of immune cells, such as macrophages and microglia, resident macrophages in the brain.
Dr. Nomura’s doctoral studies at the École Polytechnique fédérale de Lausanne (EPFL) focused on studies of how bile acid signaling shapes macrophage function in metabolic diseases. As a postdoctoral fellow at the National Institutes of Health (NIH), his focus was on understanding the role of macrophage FAO in metabolism.
Dr. Nomura is originally from Japan and loves physical exercise and hopes to run the Bridge to Bridge marathon sometime in 2022. If you see a man running up the Buck Institute’s steep hillside, the guy is likely Mitsu.
S. P.Sawyer Peralta Research Associate
Stepahanie Roa Diaz Research Associate
Stephanie is a Research Associate at the Buck Institute for Research on Aging. She completed her B.S. in Biochemistry at Sonoma State University (Fall 2019) where her undergraduate research focus was on elucidating protein-RNA interactions of a potential therapeutic agent for Non-Hodgkin’s Lymphoma (Dr. Lares’s Lab). Her current research focus at the Newman lab is investigating how BHB regulates proteins in the brain through the regulation of protein homeostasis; which lowers with age. She aims to contribute to the health and well-being of her community through health advocacy, collaborative thinking and innovation. She considers herself a lifelong learner and looks forward to aging with her loved ones.
Lexi Straube Laboratory Technician
Lexi began in the Newman Lab as an intern in 2018. After one year of rigorous apprentice work, she was hired as a lab technician. She earned two associate degrees from the Santa Rosa Junior College in biology and natural sciences. Lexi transferred to Stanford University in 2020 and is currently continuing her education as a Human Biology major with a concentration in Neurobiology, Behavior, and Health in order to ultimately become a medical doctor. Her work in the Newman lab involves exploring the potential of beta-hydroxybutyrate (BHB) and its structural analogs as signaling metabolites. Lexi is currently investigating BHB’s relationship with delirium-associated energy deficits and metabolic dysfunction, in addition to, age-related disease. In her spare time, she enjoys outdoor endeavors, traveling, burying her head into textbooks (all but physics), and playing card/board games with friends and family.
D. D.Diego Diaz Research Associate
Diego began at the Newman Lab as an intern and finished in 2019 as a Lab Associate. He earned his bachelors degree in Biology with a double minor in Chemistry and Forensic Studies from San Jose State University (2021) and then joined Genentech as a research associate in 2021.
M. F.Megan Forgie Intern
Megan joined the Newman lab in January 2021 as a lab intern and worked alongside other members until July 2021. She left the lab to attend Western University’s College of Osteopathic Medicine of the Pacific to pursue a career in preventive and lifestyle medicine. She is passionate about nutrition, healthy living/aging, and regenerative agriculture and spends her spare time riding horses, hiking with her dog, and gardening.
O. P.Oishika Panda, Ph.D. Postdoctoral Research Fellow
Dr. Panda joined the Buck in February 2018, after her Ph.D. in chemistry and chemical biology from Cornell University, Ithaca, New York. Having grown up in hot and humid Kolkata, India, and done her graduate studies in snowy-for-8-months-of-the-year Upstate New York, she has mixed feelings about the Bay Area weather! Dr. Panda is interested in applying her analytical chemistry skills to study the regulation of posttranslational acylations of proteins by endogenous metabolites, and their signaling functions. In her spare time, she enjoys trying out new cheesecake recipes, playing with cats and dogs, and discussing Harry Potter and Middle Earth trivia with whoever wants to listen!
- Models and Studies of Aging: Executive Summary of a Report from the U13 Conference Series. Hurria A, Carpenter CR, McFarland F, Lundebjerg NE, de Cabo R, Ferrucci L, Studenski SA, Barzilai N, Briggs JP, Ix JH, Kitzman DW, Kuchel GA, Musi N, Newman JC, Rando TA, Smith AK, Walston JD, Kirkland JL, Yung R. Journal of the American Geriatrics Society. 2019; 67(3):428-433. NIHMSID: NIHMS1013523 PubMed [journal]PMID: 30693953 PMCID: PMC6403012
- Newman, J. C., Covarrubias, A. J., Zhao, M., Yu, X., Gut, P., Ng, C. P., Huang, Y., Haldar, S., Verdin, E. (2017). Ketogenic diet reduces mid-life mortality and improves memory in aging mice. Cell Metab, 26(3), 547–57, e8.
- Tognini, P., Murakami, M., Liu, Y., Eckle-Mahan, K. L., Newman, J. C., Verdin, E., Baldi, P., Sassone-Corsi, P. (2017). Distinct circadian signatures in liver and gut clocks revealed by ketogenic diet. Cell Metab, 26(3), 523–538, e5.
- Newman, J. C., Verdin, E. (2017). Beta-hydroxybutyrate: A signaling molecule. Ann Rev Nutr, 37, 51–76.
- Newman, J. C., Kroll, F., Ulrich, S., Palop, J. J., Verdin, E. (2017 May 9).Ketogenic diet or BHB improves epileptiform spikes, memory, survival in Alzheimer’s model. bioRxiv, 136226. DOI: https://doi.org/10.1101/136226
- Newman, J. C., Verdin, E. Ketone bodies as signaling metabolites. (2014). Trends Endocrinol Metab, 25(1), 42–52.
- Shimazu ,T., Hirschey, M. D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C. A., Lim, H., Saunders, L. R., Stevens R. D., Newgard, C. B., Farese, R. V., de Cabo, R., Ulrich, S., Akassoglou, K., Verdin, E. (2013). Suppression of oxidative stress by b-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science, 339(6116), 211–4.
- Newman, J. C.*, Justice, J.*, Miller, J. D.*, Hashmi, S. K., Halter, J., Austad, S. N., Barzilai, N., Kirkland, J. L. (2016). Frameworks for proof-of-concept clinical trials of interventions that target fundamental aging processes. J Gerontol A Biol Sci Med Sci, 71(11), 1415-1423.
- Newman, J. C.*, Milman, S.*, Hashmi, S. K., Austad, S. N., Kirkland, J. L., Halter, J. B., Barzilai, N. (2016). Strategies and challenges in clinical trials targeting human aging. J Gerontol A Biol Sci Med Sci, 71(11), 1424–1434.
- Newman, J. C. (2015). Copyright and bedside cognitive testing: Why we need alternatives to the Mini-Mental State Examination. JAMA Intern Med, 175(9), 1459–60.
- Feldman, R., Newman, J. (2013). Copyright at the bedside: Should we stop the spread? Stan Tech L Rev, 16, 623.
- Newman, J. C., Feldman, R. (2011). Copyright and open access at the bedside. New Eng J Med, 365(26), 2447–9.
Dr. Newman’s Pubmed link