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Blazing a trail for the clinical use of rapamycin as a geroprotecTOR.
Konopka AR, Lamming DW; RAP PAC Investigators; EVERLAST Investigators. Konopka AR, et al. Among authors: lamming dw. Geroscience. 2023 Oct;45(5):2769-2783. doi: 10.1007/s11357-023-00935-x. Epub 2023 Oct 6. Geroscience. 2023. PMID: 37801202 Free PMC article.
Differences in the kinetics and molecular mechanisms by which rapamycin inhibits mTORC1 and mTORC2 suggest that a therapeutic window for rapamycin could be exploited using intermittent dosing schedules or alternative rapalogs that may enable more selective inhibition of mTORC1. H …
Differences in the kinetics and molecular mechanisms by which rapamycin inhibits mTORC1 and mTORC2 suggest that a therapeutic window for rap …
Weight Pulling: A Novel Mouse Model of Human Progressive Resistance Exercise.
Zhu WG, Hibbert JE, Lin KH, Steinert ND, Lemens JL, Jorgenson KW, Newman SM, Lamming DW, Hornberger TA. Zhu WG, et al. Among authors: lamming dw. Cells. 2021 Sep 17;10(9):2459. doi: 10.3390/cells10092459. Cells. 2021. PMID: 34572107 Free PMC article.
The relative increase in muscle mass is similar to what has been observed in human studies, and is associated with the same type of long-term adaptations that occur in humans (e.g., fiber hypertrophy, myonuclear accretion, and, in some instances, a fast-to-slow transition …
The relative increase in muscle mass is similar to what has been observed in human studies, and is associated with the same type of long- …
Agonist-independent Gαz activity negatively regulates beta-cell compensation in a diet-induced obesity model of type 2 diabetes.
Schaid MD, Green CL, Peter DC, Gallagher SJ, Guthery E, Carbajal KA, Harrington JM, Kelly GM, Reuter A, Wehner ML, Brill AL, Neuman JC, Lamming DW, Kimple ME. Schaid MD, et al. Among authors: lamming dw. J Biol Chem. 2021 Jan-Jun;296:100056. doi: 10.1074/jbc.RA120.015585. Epub 2020 Nov 24. J Biol Chem. 2021. PMID: 33172888 Free PMC article.
Full-body Galpha(z)-null mice are protected from hyperglycemia and glucose intolerance after long-term high-fat diet (HFD) feeding. In this study, at a time point in the feeding regimen where WT mice are only mildly glucose intolerant, transcriptomics analyses reveal islet …
Full-body Galpha(z)-null mice are protected from hyperglycemia and glucose intolerance after long-term high-fat diet (HFD) feeding. I …
Next Generation Strategies for Geroprotection via mTORC1 Inhibition.
Dumas SN, Lamming DW. Dumas SN, et al. Among authors: lamming dw. J Gerontol A Biol Sci Med Sci. 2020 Jan 1;75(1):14-23. doi: 10.1093/gerona/glz056. J Gerontol A Biol Sci Med Sci. 2020. PMID: 30794726 Free PMC article. Review.
Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) with the pharmaceutical rapamycin prolongs the lifespan and healthspan of model organisms including rodents, with evidence now emerging that rapamycin and its analogs may also have rejuvenative effects in dogs and h …
Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) with the pharmaceutical rapamycin prolongs the lifespan and healthspan of m …
Age-Dependent Protection of Insulin Secretion in Diet Induced Obese Mice.
De Leon ER, Brinkman JA, Fenske RJ, Gregg T, Schmidt BA, Sherman DS, Cummings NE, Peter DC, Kimple ME, Lamming DW, Merrins MJ. De Leon ER, et al. Among authors: lamming dw. Sci Rep. 2018 Dec 13;8(1):17814. doi: 10.1038/s41598-018-36289-0. Sci Rep. 2018. PMID: 30546031 Free PMC article.
To deconvolve the effects of age and obesity in an experimental model of prediabetes, we fed young and aged mice either chow or a short-term high-fat/high-sucrose Western diet (WD) and examined how weight, glucose tolerance, and beta-cell function were affected. ...
To deconvolve the effects of age and obesity in an experimental model of prediabetes, we fed young and aged mice either chow or a short-t …
Short-term methionine deprivation improves metabolic health via sexually dimorphic, mTORC1-independent mechanisms.
Yu D, Yang SE, Miller BR, Wisinski JA, Sherman DS, Brinkman JA, Tomasiewicz JL, Cummings NE, Kimple ME, Cryns VL, Lamming DW. Yu D, et al. Among authors: lamming dw. FASEB J. 2018 Jun;32(6):3471-3482. doi: 10.1096/fj.201701211R. Epub 2018 Jan 30. FASEB J. 2018. PMID: 29401631 Free PMC article.
Dietary restriction of methionine promotes leanness and improves metabolic health in mice and humans. However, poor long-term adherence to this diet limits its translational potential. In this study, we develop a short-term methionine deprivation (MD) regimen that p …
Dietary restriction of methionine promotes leanness and improves metabolic health in mice and humans. However, poor long-term adheren …
Short-term consumption of a plant protein diet does not improve glucose homeostasis of young C57BL/6J mice.
Lamming DW, Baar EL, Arriola Apelo SI, Tosti V, Fontana L. Lamming DW, et al. Nutr Healthy Aging. 2017 Dec 7;4(3):239-245. doi: 10.3233/NHA-170025. Nutr Healthy Aging. 2017. PMID: 29276793 Free PMC article.
We find that male C57BL/6J mice consuming either diet have similar glycemic control, as assessed by glucose, insulin, and pyruvate tolerance tests, and have similar overall body composition. We conclude that short-term feeding of plant protein has no positive or negative e …
We find that male C57BL/6J mice consuming either diet have similar glycemic control, as assessed by glucose, insulin, and pyruvate tolerance …
Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system.
Arriola Apelo SI, Neuman JC, Baar EL, Syed FA, Cummings NE, Brar HK, Pumper CP, Kimple ME, Lamming DW. Arriola Apelo SI, et al. Among authors: lamming dw. Aging Cell. 2016 Feb;15(1):28-38. doi: 10.1111/acel.12405. Epub 2015 Oct 13. Aging Cell. 2016. PMID: 26463117 Free PMC article.
Unfortunately, rapamycin has potentially serious side effects in humans, including glucose intolerance and immunosuppression, which may preclude the long-term prophylactic use of rapamycin as a therapy for age-related diseases. ...
Unfortunately, rapamycin has potentially serious side effects in humans, including glucose intolerance and immunosuppression, which may prec …
Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile.
Mercken EM, Crosby SD, Lamming DW, JeBailey L, Krzysik-Walker S, Villareal DT, Capri M, Franceschi C, Zhang Y, Becker K, Sabatini DM, de Cabo R, Fontana L. Mercken EM, et al. Among authors: lamming dw. Aging Cell. 2013 Aug;12(4):645-51. doi: 10.1111/acel.12088. Epub 2013 Jun 5. Aging Cell. 2013. PMID: 23601134 Free PMC article.
However, little is known about the molecular adaptations induced by CR in humans. Here, we report that long-term CR in humans inhibits the IGF-1/insulin pathway in skeletal muscle, a key metabolic tissue. ...
However, little is known about the molecular adaptations induced by CR in humans. Here, we report that long-term CR in humans inhibit …