Dudley Lamming

Research Description:
Our goal is to understand how nutrient-responsive signaling pathways can be harnessed to promote health and longevity. Our recent work has focused on the role of dietary protein in regulating healthy aging; we have found that altering levels of specific dietary amino acids can improve metabolic health, reduce frailty and extend lifespan. We also investigate how rapamycin, an inhibitor of the protein kinase mTOR, regulates healthy aging in model organisms and in humans. In all of our studies, we utilize a genetics approach, using genetic mouse models to gain mechanistic insight and harnessing natural genetic variation to identify key mediators of the effects of diets and mTOR inhibitors on healthy aging and age-related diseases, including diabetes, obesity, and Alzheimer’s disease.

Representative Publications:
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Green CL, Trautman ME, Babygirija R, Jain R, Chaiyakul K, Pak HH, Bleicher A, Novak G, Sonsalla MM, Yeh C-Y, Calubag MF, Liu TT, Flores V, Newman S, Ricke WA, Matkowskyj KA, Ong IM, Simcox J, Lamming DW. Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice. Cell Metabolism. 2023 Nov 7;35(11):1976-1995.e6. doi: 10.1016/j.cmet.2023.10.005. PMID: 37939658 PMCID: PMC10655617

Green CL, Pak HH, Richardson NE, Flores V, Yu D, Tomasiewicz JL, Dumas SN, Kredell K, Fan JW, Kirsh C, Chaiyakul K, Murphy ME, Babygirija R, Barrett-Wilt GA, Rabinowitz J, Ong IM, Jang C, Simcox J, Lamming DW. Sex and genetic background define the metabolic, physiologic, and molecular response to protein restriction. Cell Metab. 2022 Feb 1;34(2):209-226.e5. doi: 10.1016/j.cmet.2021.12.018. PMID: 35108511; PMCID: PMC8865085.

Pak HH, Haws SA, Green CL, Koller M, Lavarias MT, Richardson NE, Yang SE, Dumas SN, Sonsalla M, Bray L, Johnson M, Barnes S, Darley-Usmar V, Zhang J, Yen CE, Denu JM, Lamming DW. Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice. Nat Metab. 2021 Oct;3(10):1327-1341. doi: 10.1038/s42255-021-00466-9. Epub 2021 Oct 18. PMID: 34663973; PMCID: PMC8544824.

Yu D, Richardson NE, Green CL, Spicer AB, Murphy ME, Flores V, Jang C, Kasza I, Nikodemova M, Wakai MH, Tomasiewicz JL, Yang SE, Miller BR, Pak HH, Brinkman JA, Rojas JM, Quinn WJ 3rd, Cheng EP, Konon EN, Haider LR, Finke M, Sonsalla M, Alexander CM, Rabinowitz JD, Baur JA, Malecki KC, Lamming DW. The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. Cell Metab. 2021 May 4;33(5):905-922.e6. doi: 10.1016/j.cmet.2021.03.025. Epub 2021 Apr 21. PMID: 33887198; PMCID: PMC8102360.

Richardson NE, Konon EN, Schuster HS, Mitchell AT, Boyle C, Rodgers AC, Finke M, Haider LR, Yu D, Flores V, Pak HH, Ahmad S, Ahmed S, Radcliff A, Wu J, Williams EM, Abdi L, Sherman DS, Hacker T, Lamming DW. Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and lifespan in mice. Nat Aging. 2021 Jan;1(1):73-86. doi: 10.1038/s43587-020-00006-2. Epub 2021 Jan 14. PMID: 33796866; PMCID: PMC8009080.