{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:10:41Z","timestamp":1791591041979,"version":"4.3.4"},"reference-count":203,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG056771"],"award-info":[{"award-number":["AG056771"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG081482"],"award-info":[{"award-number":["AG081482"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG084156"],"award-info":[{"award-number":["AG084156"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG085898"],"award-info":[{"award-number":["AG085898"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG094153"],"award-info":[{"award-number":["AG094153"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["GeroScience"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Almost a century ago, calorie restriction (CR) was identified as a robust intervention for extending lifespan and healthspan, a discovery that captured the imagination of both scientists and the public. If the powerful mechanisms engaged by CR can be uncovered and harnessed through a pill, humans might be able to live longer and healthier lives. Here, we will discuss the evolution of rapamycin, an inhibitor of the mTOR (mechanistic Target Of Rapamycin) protein kinase, from an immunosuppressant to the most reproducible pharmacological geroprotector in geroscience. This is a rapidly evolving field, with the number of basic science studies, clinical trials, and off-label use of mTOR inhibitors by the general public expanding quickly. We review findings in model organisms that have revealed potent benefits of rapamycin not only for longevity but for the function of multiple organ systems and on the hallmarks of aging. We review completed and ongoing clinical trials of rapamycin and analogs for diseases of aging in humans, and discuss the challenges and side-effects of rapamycin that may limit its translation from the laboratory to the clinic. While the jury is still out, we conclude that rapamycin\u2014or molecules that similarly act to inhibit mTOR\u2014may yet realize the century-old dream of extending healthspan and lifespan with a small molecule.<\/jats:p>","DOI":"10.1007\/s11357-026-02306-8","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T11:34:17Z","timestamp":1778672057000},"page":"4547-4570","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bench to bedside: is rapamycin headed for the docTOR?"],"prefix":"10.1007","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0079-4467","authenticated-orcid":false,"given":"Dudley W.","family":"Lamming","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"2306_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4557","volume":"5","author":"RJ Colman","year":"2014","unstructured":"Colman RJ, Beasley TM, Kemnitz JW, Johnson SC, Weindruch R, Anderson RM. Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun. 2014;5:3557.","journal-title":"Nat Commun"},{"issue":"5976","key":"2306_CR2","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1126\/science.1172539","volume":"328","author":"L Fontana","year":"2010","unstructured":"Fontana L, Partridge L, Longo VD. Extending healthy life span-from yeast to humans. Science. 2010;328(5976):321\u20136.","journal-title":"Science"},{"issue":"7","key":"2306_CR3","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.18632\/aging.100994","volume":"8","author":"SN Meydani","year":"2016","unstructured":"Meydani SN, Das SK, Pieper CF, Lewis MR, Klein S, Dixit VD, et al. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans. Aging (Albany NY). 2016;8(7):1416\u201331.","journal-title":"Aging (Albany NY)"},{"issue":"6581","key":"2306_CR4","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1126\/science.abg7292","volume":"375","author":"O Spadaro","year":"2022","unstructured":"Spadaro O, Youm Y, Shchukina I, Ryu S, Sidorov S, Ravussin A, et al. Caloric restriction in humans reveals immunometabolic regulators of health span. Science. 2022;375(6581):671\u20137.","journal-title":"Science"},{"issue":"5","key":"2306_CR5","doi-asserted-by":"publisher","first-page":"4203","DOI":"10.1007\/s11357-024-01200-5","volume":"46","author":"DW Lamming","year":"2024","unstructured":"Lamming DW. Quantification of healthspan in aging mice: introducing FAMY and GRAIL. Geroscience. 2024;46(5):4203\u201315.","journal-title":"Geroscience"},{"issue":"1","key":"2306_CR6","doi-asserted-by":"publisher","first-page":"7147","DOI":"10.1038\/s41467-025-62416-3","volume":"16","author":"R Babygirija","year":"2025","unstructured":"Babygirija R, Han JH, Sonsalla MM, Matoska R, Calubag MF, Green CL, et al. Fasting is required for many of the benefits of calorie restriction in the 3xTg mouse model of Alzheimer\u2019s disease. Nat Commun. 2025;16(1):7147.","journal-title":"Nat Commun"},{"issue":"4","key":"2306_CR7","doi-asserted-by":"publisher","first-page":"417","DOI":"10.3233\/JAD-2006-10411","volume":"10","author":"W Qin","year":"2006","unstructured":"Qin W, Chachich M, Lane M, Roth G, Bryant M, de Cabo R, et al. Calorie restriction attenuates Alzheimer\u2019s disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus). Journal of Alzheimer\u2019s disease\u202f: JAD. 2006;10(4):417\u201322.","journal-title":"Journal of Alzheimer\u2019s disease : JAD"},{"issue":"7","key":"2306_CR8","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1016\/j.cmet.2023.06.008","volume":"35","author":"MM Mihaylova","year":"2023","unstructured":"Mihaylova MM, Chaix A, Delibegovic M, Ramsey JJ, Bass J, Melkani G, et al. When a calorie is not just a calorie: diet quality and timing as mediators of metabolism and healthy aging. Cell Metab. 2023;35(7):1114\u201331.","journal-title":"Cell Metab"},{"issue":"10","key":"2306_CR9","doi-asserted-by":"publisher","first-page":"721","DOI":"10.7164\/antibiotics.28.721","volume":"28","author":"C Vezina","year":"1975","unstructured":"Vezina C, Kudelski A, Sehgal SN. Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J Antibiot (Tokyo). 1975;28(10):721\u20136.","journal-title":"J Antibiot (Tokyo)"},{"issue":"1","key":"2306_CR10","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/tra.12617","volume":"20","author":"DW Lamming","year":"2019","unstructured":"Lamming DW, Bar-Peled L. Lysosome: the metabolic signaling hub. Traffic. 2019;20(1):27\u201338.","journal-title":"Traffic"},{"issue":"6","key":"2306_CR11","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.devcel.2022.02.024","volume":"57","author":"J Simcox","year":"2022","unstructured":"Simcox J, Lamming DW. The central moTOR of metabolism. Dev Cell. 2022;57(6):691\u2013706.","journal-title":"Dev Cell"},{"issue":"6967","key":"2306_CR12","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1038\/426620a","volume":"426","author":"T Vellai","year":"2003","unstructured":"Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Muller F. Genetics: influence of TOR kinase on lifespan in C. elegans. Nature. 2003;426(6967):620.","journal-title":"Nature"},{"issue":"5751","key":"2306_CR13","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1126\/science.1115535","volume":"310","author":"M Kaeberlein","year":"2005","unstructured":"Kaeberlein M, Powers RW 3rd, Steffen KK, Westman EA, Hu D, Dang N, et al. Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science. 2005;310(5751):1193\u20136.","journal-title":"Science"},{"issue":"10","key":"2306_CR14","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.cub.2004.03.059","volume":"14","author":"P Kapahi","year":"2004","unstructured":"Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol. 2004;14(10):885\u201390.","journal-title":"Curr Biol"},{"issue":"2","key":"2306_CR15","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1101\/gad.1381406","volume":"20","author":"RW Powers 3rd","year":"2006","unstructured":"Powers RW 3rd, Kaeberlein M, Caldwell SD, Kennedy BK, Fields S. Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev. 2006;20(2):174\u201384.","journal-title":"Genes Dev"},{"issue":"1","key":"2306_CR16","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1111\/j.1474-9726.2006.00267.x","volume":"6","author":"M Hansen","year":"2007","unstructured":"Hansen M, Taubert S, Crawford D, Libina N, Lee SJ, Kenyon C. Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell. 2007;6(1):95\u2013110.","journal-title":"Aging Cell"},{"issue":"7130","key":"2306_CR17","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1038\/nature05603","volume":"445","author":"P Syntichaki","year":"2007","unstructured":"Syntichaki P, Troulinaki K, Tavernarakis N. eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans. Nature. 2007;445(7130):922\u20136.","journal-title":"Nature"},{"issue":"3","key":"2306_CR18","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1093\/gerona\/60.3.293","volume":"60","author":"ZD Sharp","year":"2005","unstructured":"Sharp ZD, Bartke A. Evidence for down-regulation of phosphoinositide 3-kinase\/Akt\/mammalian target of rapamycin (PI3K\/Akt\/mTOR)-dependent translation regulatory signaling pathways in Ames dwarf mice. J Gerontol A Biol Sci Med Sci. 2005;60(3):293\u2013300.","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"6076","key":"2306_CR19","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1126\/science.1215135","volume":"335","author":"DW Lamming","year":"2012","unstructured":"Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, et al. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. 2012;335(6076):1638\u201343.","journal-title":"Science"},{"issue":"5","key":"2306_CR20","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.celrep.2013.07.030","volume":"4","author":"JJ Wu","year":"2013","unstructured":"Wu JJ, Liu J, Chen EB, Wang JJ, Cao L, Narayan N, et al. Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression. Cell Rep. 2013;4(5):913\u201320.","journal-title":"Cell Rep"},{"issue":"1","key":"2306_CR21","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/s41598-017-00970-7","volume":"7","author":"HM Zhang","year":"2017","unstructured":"Zhang HM, Diaz V, Walsh ME, Zhang Y. Moderate lifelong overexpression of tuberous sclerosis complex 1 (TSC1) improves health and survival in mice. Sci Rep. 2017;7(1):834.","journal-title":"Sci Rep"},{"issue":"5949","key":"2306_CR22","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1126\/science.1177221","volume":"326","author":"C Selman","year":"2009","unstructured":"Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ, Choudhury AI, et al. Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science. 2009;326(5949):140\u20134.","journal-title":"Science"},{"issue":"7641","key":"2306_CR23","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nature21380","volume":"542","author":"A Arif","year":"2017","unstructured":"Arif A, Terenzi F, Potdar AA, Jia J, Sacks J, China A, et al. EPRS is a critical mTORC1-S6K1 effector that influences adiposity in mice. Nature. 2017;542(7641):357\u201361.","journal-title":"Nature"},{"issue":"7","key":"2306_CR24","doi-asserted-by":"publisher","first-page":"1903","DOI":"10.1016\/j.celrep.2016.07.029","volume":"16","author":"SY Tsai","year":"2016","unstructured":"Tsai SY, Rodriguez AA, Dastidar SG, Del Greco E, Carr KL, Sitzmann JM, et al. Increased 4E-BP1 expression protects against diet-induced obesity and insulin resistance in male mice. Cell Rep. 2016;16(7):1903\u201314.","journal-title":"Cell Rep"},{"issue":"8","key":"2306_CR25","doi-asserted-by":"publisher","first-page":"2952","DOI":"10.1172\/JCI77361","volume":"125","author":"S Tsai","year":"2015","unstructured":"Tsai S, Sitzmann JM, Dastidar SG, Rodriguez AA, Vu SL, McDonald CE, et al. Muscle-specific 4E-BP1 signaling activation improves metabolic parameters during aging and obesity. J Clin Invest. 2015;125(8):2952\u201364.","journal-title":"J Clin Invest"},{"issue":"1","key":"2306_CR26","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.cmet.2009.11.010","volume":"11","author":"I Bjedov","year":"2010","unstructured":"Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, et al. Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab. 2010;11(1):35\u201346.","journal-title":"Cell Metab"},{"issue":"2","key":"2306_CR27","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/acel.12175","volume":"13","author":"WC Fok","year":"2014","unstructured":"Fok WC, Bokov A, Gelfond J, Yu Z, Zhang Y, Doderer M, et al. Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver. Aging Cell. 2014;13(2):311\u20139.","journal-title":"Aging Cell"},{"key":"2306_CR28","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.mad.2014.07.004","volume":"140","author":"WC Fok","year":"2014","unstructured":"Fok WC, Livi C, Bokov A, Yu Z, Chen Y, Richardson A, et al. Short-term rapamycin treatment in mice has few effects on the transcriptome of white adipose tissue compared to dietary restriction. Mech Ageing Dev. 2014;140:23\u20139.","journal-title":"Mech Ageing Dev"},{"issue":"2","key":"2306_CR29","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1093\/gerona\/gls127","volume":"68","author":"WC Fok","year":"2013","unstructured":"Fok WC, Zhang Y, Salmon AB, Bhattacharya A, Gunda R, Jones D, et al. Short-term treatment with rapamycin and dietary restriction have overlapping and distinctive effects in young mice. J Gerontol A Biol Sci Med Sci. 2013;68(2):108\u201316.","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"9","key":"2306_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114663","volume":"43","author":"HH Pak","year":"2024","unstructured":"Pak HH, Grossberg AN, Sanderfoot RR, Babygirija R, Green CL, Koller M, et al. Non-canonical metabolic and molecular effects of calorie restriction are revealed by varying temporal conditions. Cell Rep. 2024;43(9):114663.","journal-title":"Cell Rep"},{"issue":"7253","key":"2306_CR31","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/nature08221","volume":"460","author":"DE Harrison","year":"2009","unstructured":"Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460(7253):392\u20135.","journal-title":"Nature"},{"issue":"5","key":"2306_CR32","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/j.cmet.2012.04.007","volume":"15","author":"S Robida-Stubbs","year":"2012","unstructured":"Robida-Stubbs S, Glover-Cutter K, Lamming DW, Mizunuma M, Narasimhan SD, Neumann-Haefelin E, et al. TOR signaling and rapamycin influence longevity by regulating SKN-1\/Nrf and DAF-16\/FoxO. Cell Metab. 2012;15(5):713\u201324.","journal-title":"Cell Metab"},{"issue":"10","key":"2306_CR33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0050261","volume":"5","author":"O Medvedik","year":"2007","unstructured":"Medvedik O, Lamming DW, Kim KD, Sinclair DA. MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae. PLoS Biol. 2007;5(10):e261.","journal-title":"PLoS Biol"},{"issue":"7","key":"2306_CR34","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1093\/gerona\/glw064","volume":"71","author":"SI Arriola Apelo","year":"2016","unstructured":"Arriola Apelo SI, Pumper CP, Baar EL, Cummings NE, Lamming DW. Intermittent administration of rapamycin extends the life span of female C57BL\/6J mice. J Gerontol A Biol Sci Med Sci. 2016;71(7):876\u201381.","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"37","key":"2306_CR35","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo5482","volume":"8","author":"AV Shindyapina","year":"2022","unstructured":"Shindyapina AV, Cho Y, Kaya A, Tyshkovskiy A, Castro JP, Deik A, et al. Rapamycin treatment during development extends life span and health span of male mice and Daphnia magna. Sci Adv. 2022;8(37):eabo5482.","journal-title":"Sci Adv"},{"key":"2306_CR36","doi-asserted-by":"crossref","unstructured":"Bitto A, Ito TK, Pineda VV, LeTexier NJ, Huang HZ, Sutlief E, et al. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. eLife. 2016;5.","DOI":"10.7554\/eLife.16351"},{"issue":"9","key":"2306_CR37","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202255299","volume":"23","author":"G Aiello","year":"2022","unstructured":"Aiello G, Sabino C, Pernici D, Audano M, Antonica F, Gianesello M, et al. Transient rapamycin treatment during developmental stage extends lifespan in Mus musculus and Drosophila melanogaster. EMBO Rep. 2022;23(9):e55299.","journal-title":"EMBO Rep"},{"issue":"1","key":"2306_CR38","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1093\/gerona\/glz060","volume":"75","author":"A Unnikrishnan","year":"2020","unstructured":"Unnikrishnan A, Kurup K, Salmon AB, Richardson A. Is rapamycin a dietary restriction mimetic? J Gerontol A Biol Sci Med Sci. 2020;75(1):4\u201313.","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"7","key":"2306_CR39","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1038\/s43587-025-00876-4","volume":"5","author":"L Gkioni","year":"2025","unstructured":"Gkioni L, Nespital T, Baghdadi M, Monzo C, Bali J, Nassr T, et al. The geroprotectors trametinib and rapamycin combine additively to extend mouse healthspan and lifespan. Nat Aging. 2025;5(7):1249\u201365.","journal-title":"Nat Aging"},{"issue":"12","key":"2306_CR40","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13724","volume":"21","author":"R Strong","year":"2022","unstructured":"Strong R, Miller RA, Cheng CJ, Nelson JF, Gelfond J, Allani SK, et al. Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice. Aging Cell. 2022;21(12):e13724.","journal-title":"Aging Cell"},{"issue":"3","key":"2306_CR41","doi-asserted-by":"publisher","first-page":"2851","DOI":"10.1007\/s11357-024-01484-7","volume":"47","author":"AE Coleman","year":"2025","unstructured":"Coleman AE, Creevy KE, Anderson R, Reed MJ, Fajt VR, Aicher KM, et al. Test of Rapamycin in Aging Dogs (TRIAD): study design and rationale for a prospective, parallel-group, double-masked, randomized, placebo-controlled, multicenter trial of rapamycin in healthy middle-aged dogs from the Dog Aging Project. Geroscience. 2025;47(3):2851\u201377.","journal-title":"Geroscience"},{"key":"2306_CR42","doi-asserted-by":"publisher","first-page":"1168711","DOI":"10.3389\/fvets.2023.1168711","volume":"10","author":"BG Barnett","year":"2023","unstructured":"Barnett BG, Wesselowski SR, Gordon SG, Saunders AB, Promislow DEL, Schwartz SM, et al. A masked, placebo-controlled, randomized clinical trial evaluating safety and the effect on cardiac function of low-dose rapamycin in 17 healthy client-owned dogs. Front Vet Sci. 2023;10:1168711.","journal-title":"Front Vet Sci"},{"key":"2306_CR43","unstructured":"RapAdmin. Breaking: 15% Healthy Lifespan improvement via Rapamycin seen in Marmosets 2024 [updated 06\/04\/2024. Available from: https:\/\/www.rapamycin.news\/t\/breaking-15-healthy-lifespan-improvement-via-rapamycin-seen-in-marmosets\/14325."},{"issue":"7","key":"2306_CR44","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1681\/ASN.2007111202","volume":"19","author":"O Johnston","year":"2008","unstructured":"Johnston O, Rose CL, Webster AC, Gill JS. Sirolimus is associated with new-onset diabetes in kidney transplant recipients. J Am Soc Nephrol. 2008;19(7):1411\u20138.","journal-title":"J Am Soc Nephrol"},{"issue":"8","key":"2306_CR45","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1194\/jlr.M100392-JLR200","volume":"43","author":"JD Morrisett","year":"2002","unstructured":"Morrisett JD, Abdel-Fattah G, Hoogeveen R, Mitchell E, Ballantyne CM, Pownall HJ, et al. Effects of sirolimus on plasma lipids, lipoprotein levels, and fatty acid metabolism in renal transplant patients. J Lipid Res. 2002;43(8):1170\u201380.","journal-title":"J Lipid Res"},{"issue":"9","key":"2306_CR46","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1111\/j.1365-2036.2004.01923.x","volume":"19","author":"RJ Firpi","year":"2004","unstructured":"Firpi RJ, Tran TT, Flores P, Nissen N, Colquhoun S, Shackleton C, et al. Sirolimus-induced hyperlipidaemia in liver transplant recipients is not dose-dependent. Aliment Pharmacol Ther. 2004;19(9):1033\u20139.","journal-title":"Aliment Pharmacol Ther"},{"issue":"2 Suppl","key":"2306_CR47","doi-asserted-by":"publisher","first-page":"495S","DOI":"10.1016\/j.transproceed.2004.01.015","volume":"36","author":"RN Formica Jr","year":"2004","unstructured":"Formica RN Jr, Lorber KM, Friedman AL, Bia MJ, Lakkis F, Smith JD, et al. The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004;36(2 Suppl):495S-S499.","journal-title":"Transplant Proc"},{"issue":"6","key":"2306_CR48","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.2337\/db09-1324","volume":"59","author":"VP Houde","year":"2010","unstructured":"Houde VP, Brule S, Festuccia WT, Blanchard PG, Bellmann K, Deshaies Y, et al. Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue. Diabetes. 2010;59(6):1338\u201348.","journal-title":"Diabetes"},{"issue":"7170","key":"2306_CR49","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1038\/nature06322","volume":"450","author":"JT Cunningham","year":"2007","unstructured":"Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature. 2007;450(7170):736\u201340.","journal-title":"Nature"},{"key":"2306_CR50","doi-asserted-by":"crossref","unstructured":"Palliyaguru DL, Shiroma EJ, Nam JK, Duregon E, Vieira Ligo Teixeira C, Price NL, et al. Fasting blood glucose as a predictor of mortality: lost in translation. Cell Metab. 2021;33(11):2189\u2013200 e3.","DOI":"10.1016\/j.cmet.2021.08.013"},{"issue":"11","key":"2306_CR51","doi-asserted-by":"publisher","first-page":"4947","DOI":"10.1073\/pnas.92.11.4947","volume":"92","author":"J Chen","year":"1995","unstructured":"Chen J, Zheng XF, Brown EJ, Schreiber SL. Identification of an 11-kDa FKBP12-rapamycin-binding domain within the 289-kDa FKBP12-rapamycin-associated protein and characterization of a critical serine residue. Proc Natl Acad Sci U S A. 1995;92(11):4947\u201351.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"Pt 4","key":"2306_CR52","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1107\/S0907444998014747","volume":"55","author":"J Liang","year":"1999","unstructured":"Liang J, Choi J, Clardy J. Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A resolution. Acta Crystallogr D Biol Crystallogr. 1999;55(Pt 4):736\u201344.","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"5","key":"2306_CR53","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/j.molcel.2010.05.017","volume":"38","author":"CK Yip","year":"2010","unstructured":"Yip CK, Murata K, Walz T, Sabatini DM, Kang SA. Structure of the human mTOR complex I and its implications for rapamycin inhibition. Mol Cell. 2010;38(5):768\u201374.","journal-title":"Mol Cell"},{"issue":"5","key":"2306_CR54","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/s41422-018-0029-3","volume":"28","author":"X Chen","year":"2018","unstructured":"Chen X, Liu M, Tian Y, Li J, Qi Y, Zhao D, et al. Cryo-EM structure of human mTOR complex 2. Cell Res. 2018;28(5):518\u201328.","journal-title":"Cell Res"},{"key":"2306_CR55","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc1251","author":"A Scaiola","year":"2020","unstructured":"Scaiola A, Mangia F, Imseng S, Boehringer D, Berneiser K, Shimobayashi M, et al. The 3.2-A resolution structure of human mTORC2. Sci Adv. 2020. https:\/\/doi.org\/10.1126\/sciadv.abc1251.","journal-title":"Sci Adv"},{"issue":"2","key":"2306_CR56","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.molcel.2006.03.029","volume":"22","author":"DD Sarbassov","year":"2006","unstructured":"Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, et al. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt\/PKB. Mol Cell. 2006;22(2):159\u201368.","journal-title":"Mol Cell"},{"issue":"2","key":"2306_CR57","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1111\/acel.12313","volume":"14","author":"KH Schreiber","year":"2015","unstructured":"Schreiber KH, Ortiz D, Academia EC, Anies AC, Liao CY, Kennedy BK. Rapamycin-mediated mTORC2 inhibition is determined by the relative expression of FK506-binding proteins. Aging Cell. 2015;14(2):265\u201373.","journal-title":"Aging Cell"},{"issue":"6","key":"2306_CR58","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.molmet.2014.06.004","volume":"3","author":"M Kleinert","year":"2014","unstructured":"Kleinert M, Sylow L, Fazakerley DJ, Krycer JR, Thomas KC, Oxboll AJ, et al. Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo. Molecular metabolism. 2014;3(6):630\u201341.","journal-title":"Molecular metabolism"},{"issue":"1","key":"2306_CR59","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.celrep.2019.08.084","volume":"29","author":"D Yu","year":"2019","unstructured":"Yu D, Tomasiewicz JL, Yang SE, Miller BR, Wakai MH, Sherman DS, et al. Calorie-restriction-induced insulin sensitivity is mediated by adipose mTORC2 and not required for lifespan extension. Cell Rep. 2019;29(1):236-48 e3.","journal-title":"Cell Rep"},{"issue":"1","key":"2306_CR60","doi-asserted-by":"publisher","first-page":"3194","DOI":"10.1038\/s41467-019-11174-0","volume":"10","author":"KH Schreiber","year":"2019","unstructured":"Schreiber KH, Arriola Apelo SI, Yu D, Brinkman JA, Velarde MC, Syed FA, et al. A novel rapamycin analog is highly selective for mTORC1 in vivo. Nat Commun. 2019;10(1):3194.","journal-title":"Nat Commun"},{"issue":"5","key":"2306_CR61","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1111\/acel.12256","volume":"13","author":"DW Lamming","year":"2014","unstructured":"Lamming DW, Mihaylova MM, Katajisto P, Baar EL, Yilmaz OH, Hutchins A, et al. Depletion of Rictor, an essential protein component of mTORC2, decreases male lifespan. Aging Cell. 2014;13(5):911\u20137.","journal-title":"Aging Cell"},{"issue":"5","key":"2306_CR62","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13014","volume":"18","author":"K Chellappa","year":"2019","unstructured":"Chellappa K, Brinkman JA, Mukherjee S, Morrison M, Alotaibi MI, Carbajal KA, et al. Hypothalamic mTORC2 is essential for metabolic health and longevity. Aging Cell. 2019;18(5):e13014.","journal-title":"Aging Cell"},{"issue":"10","key":"2306_CR63","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1080\/15548627.2019.1704117","volume":"16","author":"K Chang","year":"2020","unstructured":"Chang K, Kang P, Liu Y, Huang K, Miao T, Sagona AP, et al. TGFB-INHB\/activin signaling regulates age-dependent autophagy and cardiac health through inhibition of MTORC2. Autophagy. 2020;16(10):1807\u201322.","journal-title":"Autophagy"},{"key":"2306_CR64","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.866210","volume":"10","author":"P Liu","year":"2022","unstructured":"Liu P, Chang K, Requejo G, Bai H. mTORC2 protects the heart from high-fat diet-induced cardiomyopathy through mitochondrial fission in Drosophila. Front Cell Dev Biol. 2022;10:866210.","journal-title":"Front Cell Dev Biol"},{"issue":"5","key":"2306_CR65","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1111\/acel.12248","volume":"13","author":"M Mizunuma","year":"2014","unstructured":"Mizunuma M, Neumann-Haefelin E, Moroz N, Li Y, Blackwell TK. mTORC2-SGK-1 acts in two environmentally responsive pathways with opposing effects on longevity. Aging Cell. 2014;13(5):869\u201378.","journal-title":"Aging Cell"},{"issue":"2","key":"2306_CR66","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.cell.2019.02.013","volume":"177","author":"B Zhou","year":"2019","unstructured":"Zhou B, Kreuzer J, Kumsta C, Wu L, Kamer KJ, Cedillo L, et al. Mitochondrial permeability uncouples elevated autophagy and lifespan extension. Cell. 2019;177(2):299-314 e16.","journal-title":"Cell"},{"key":"2306_CR67","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1146\/annurev-immunol-020711-075024","volume":"30","author":"JD Powell","year":"2012","unstructured":"Powell JD, Pollizzi KN, Heikamp EB, Horton MR. Regulation of immune responses by mTOR. Annu Rev Immunol. 2012;30:39\u201368.","journal-title":"Annu Rev Immunol"},{"issue":"1","key":"2306_CR68","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1111\/acel.12405","volume":"15","author":"SI Arriola Apelo","year":"2016","unstructured":"Arriola Apelo SI, Neuman JC, Baar EL, Syed FA, Cummings NE, Brar HK, et al. Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system. Aging Cell. 2016;15(1):28\u201338.","journal-title":"Aging Cell"},{"issue":"2","key":"2306_CR69","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/S0002-9440(10)63687-5","volume":"163","author":"WL An","year":"2003","unstructured":"An WL, Cowburn RF, Li L, Braak H, Alafuzoff I, Iqbal K, et al. Up-regulation of phosphorylated\/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer\u2019s disease. Am J Pathol. 2003;163(2):591\u2013607.","journal-title":"Am J Pathol"},{"issue":"5","key":"2306_CR70","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1111\/jnc.13037","volume":"133","author":"A Tramutola","year":"2015","unstructured":"Tramutola A, Triplett JC, Di Domenico F, Niedowicz DM, Murphy MP, Coccia R, et al. Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD. J Neurochem. 2015;133(5):739\u201349.","journal-title":"J Neurochem"},{"issue":"17","key":"2306_CR71","doi-asserted-by":"publisher","first-page":"13107","DOI":"10.1074\/jbc.M110.100420","volume":"285","author":"A Caccamo","year":"2010","unstructured":"Caccamo A, Majumder S, Richardson A, Strong R, Oddo S. Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. J Biol Chem. 2010;285(17):13107\u201320.","journal-title":"J Biol Chem"},{"issue":"1","key":"2306_CR72","doi-asserted-by":"publisher","first-page":"5217","DOI":"10.1038\/s41467-024-49589-z","volume":"15","author":"R Babygirija","year":"2024","unstructured":"Babygirija R, Sonsalla MM, Mill J, James I, Han JH, Green CL, et al. Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer\u2019s disease. Nat Commun. 2024;15(1):5217.","journal-title":"Nat Commun"},{"issue":"4","key":"2306_CR73","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009979","volume":"5","author":"P Spilman","year":"2010","unstructured":"Spilman P, Podlutskaya N, Hart MJ, Debnath J, Gorostiza O, Bredesen D, et al. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer\u2019s disease. PLoS ONE. 2010;5(4):e9979.","journal-title":"PLoS ONE"},{"issue":"1","key":"2306_CR74","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1177\/0271678X15621575","volume":"37","author":"AL Lin","year":"2017","unstructured":"Lin AL, Jahrling JB, Zhang W, DeRosa N, Bakshi V, Romero P, et al. Rapamycin rescues vascular, metabolic and learning deficits in apolipoprotein E4 transgenic mice with pre-symptomatic Alzheimer\u2019s disease. J Cereb Blood Flow Metab. 2017;37(1):217\u201326.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"9","key":"2306_CR75","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1038\/jcbfm.2013.82","volume":"33","author":"AL Lin","year":"2013","unstructured":"Lin AL, Zheng W, Halloran JJ, Burbank RR, Hussong SA, Hart MJ, et al. Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer\u2019s disease. J Cereb Blood Flow Metab. 2013;33(9):1412\u201321.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"9","key":"2306_CR76","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025416","volume":"6","author":"S Majumder","year":"2011","unstructured":"Majumder S, Richardson A, Strong R, Oddo S. Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits. PLoS One. 2011;6(9):e25416.","journal-title":"PLoS One"},{"key":"2306_CR77","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2025.126011","volume":"683","author":"VV Sugandhi","year":"2025","unstructured":"Sugandhi VV, Gattu K, Mundrathi V, Khairnar R, Arshad T, Kumar S, et al. Intranasal delivery of rapamycin via brain-targeting polymeric micelles for Alzheimer\u2019s disease treatment. Int J Pharm. 2025;683:126011.","journal-title":"Int J Pharm"},{"issue":"2","key":"2306_CR78","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1111\/j.1474-9726.2011.00791.x","volume":"11","author":"S Majumder","year":"2012","unstructured":"Majumder S, Caccamo A, Medina DX, Benavides AD, Javors MA, Kraig E, et al. Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL-1beta and enhancing NMDA signaling. Aging Cell. 2012;11(2):326\u201335.","journal-title":"Aging Cell"},{"key":"2306_CR79","doi-asserted-by":"crossref","unstructured":"Yin Z, Guo X, Qi Y, Li P, Liang S, Xu X, et al. Dietary restriction and rapamycin affect brain aging in mice by attenuating age-related DNA methylation changes. Genes (Basel). 2022;13(4).","DOI":"10.3390\/genes13040699"},{"issue":"11","key":"2306_CR80","doi-asserted-by":"publisher","DOI":"10.1111\/acel.70235","volume":"24","author":"S Navakkode","year":"2025","unstructured":"Navakkode S, Kennedy BK. Alpha-ketoglutarate ameliorates synaptic plasticity deficits in APP\/PS1 mice model of Alzheimer\u2019s disease. Aging Cell. 2025;24(11):e70235.","journal-title":"Aging Cell"},{"key":"2306_CR81","doi-asserted-by":"crossref","unstructured":"Oddo S, Lanza M, Casili G, Caccamo A. The role of S6K1 in aging and Alzheimer\u2019s disease: mechanistic insights and therapeutic potential. Int J Mol Sci. 2025;26(13).","DOI":"10.3390\/ijms26135923"},{"issue":"1","key":"2306_CR82","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/s43856-025-00904-9","volume":"5","author":"MM Gonzales","year":"2025","unstructured":"Gonzales MM, Garbarino VR, Kautz TF, Song X, Lopez-Cruzan M, Linehan L, et al. Rapamycin treatment for Alzheimer\u2019s disease and related dementias: a pilot phase 1 clinical trial. Commun Med (Lond). 2025;5(1):189.","journal-title":"Commun Med (Lond)"},{"key":"2306_CR83","doi-asserted-by":"publisher","unstructured":"Lin AL, Aware C, Neher C, Hamdi M, Ericsson A, Khegai O, et al. Rapamycin enhances neurovascular, peripheral metabolic, and immune function in cognitively normal, middle-aged APOE4 Carriers: genotype-dependent effects compared to non-carriers. Res Sq [Preprint]. 2025 Mar 19:rs.3.rs-6214340. https:\/\/doi.org\/10.21203\/rs.3.rs-6214340\/v1.","DOI":"10.21203\/rs.3.rs-6214340\/v1"},{"issue":"21","key":"2306_CR84","doi-asserted-by":"publisher","first-page":"2789","DOI":"10.1161\/CIRCULATIONAHA.108.822403","volume":"119","author":"DF Dai","year":"2009","unstructured":"Dai DF, Santana LF, Vermulst M, Tomazela DM, Emond MJ, MacCoss MJ, et al. Overexpression of catalase targeted to mitochondria attenuates murine cardiac aging. Circulation. 2009;119(21):2789\u201397.","journal-title":"Circulation"},{"issue":"5","key":"2306_CR85","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1111\/acel.12109","volume":"12","author":"JM Flynn","year":"2013","unstructured":"Flynn JM, O\u2019Leary MN, Zambataro CA, Academia EC, Presley MP, Garrett BJ, et al. Late-life rapamycin treatment reverses age-related heart dysfunction. Aging Cell. 2013;12(5):851\u201362.","journal-title":"Aging Cell"},{"issue":"2","key":"2306_CR86","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13086","volume":"19","author":"E Quarles","year":"2020","unstructured":"Quarles E, Basisty N, Chiao YA, Merrihew G, Gu H, Sweetwyne MT, et al. Rapamycin persistently improves cardiac function in aged, male and female mice, even following cessation of treatment. Aging Cell. 2020;19(2):e13086.","journal-title":"Aging Cell"},{"key":"2306_CR87","doi-asserted-by":"publisher","unstructured":"Chakraborty AD, Kooiker K, Kobak KA, Cheng Y, Lee CF, Razumova M, et al. Late-life rapamycin treatment enhances cardiomyocyte relaxation kinetics and reduces myocardial stiffness. bioRxiv [Preprint]. 2023 Jun 13:2023.06.12.544619. https:\/\/doi.org\/10.1101\/2023.06.12.544619.","DOI":"10.1101\/2023.06.12.544619"},{"issue":"11","key":"2306_CR88","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.2460\/javma.23.04.0187","volume":"261","author":"JL Kaplan","year":"2023","unstructured":"Kaplan JL, Rivas VN, Walker AL, Grubb L, Farrell A, Fitzgerald S, et al. Delayed-release rapamycin halts progression of left ventricular hypertrophy in subclinical feline hypertrophic cardiomyopathy: results of the RAPACAT trial. J Am Vet Med Assoc. 2023;261(11):1628\u201337.","journal-title":"J Am Vet Med Assoc"},{"issue":"2","key":"2306_CR89","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s11357-017-9972-z","volume":"39","author":"SR Urfer","year":"2017","unstructured":"Urfer SR, Kaeberlein TL, Mailheau S, Bergman PJ, Creevy KE, Promislow DEL, et al. A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs. Geroscience. 2017;39(2):117\u201327.","journal-title":"Geroscience"},{"key":"2306_CR90","doi-asserted-by":"publisher","unstructured":"Moody AJ, Wu Y, Romo TQ, Koek W, Li J, Linehan LA, et al. Short-term mTOR inhibition by rapamycin improves cardiac and endothelial function in older men: a proof-of concept pilot study. Geroscience. 2025. https:\/\/doi.org\/10.1007\/s11357-025-01855-8.","DOI":"10.1007\/s11357-025-01855-8"},{"key":"2306_CR91","doi-asserted-by":"crossref","unstructured":"Chen C, Liu Y, Liu Y, Zheng P. mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signal. 2009;2(98):ra75.","DOI":"10.1126\/scisignal.2000559"},{"key":"2306_CR92","doi-asserted-by":"publisher","first-page":"1682406","DOI":"10.3389\/fimmu.2025.1682406","volume":"16","author":"LAD Queiroz","year":"2025","unstructured":"Queiroz LAD, Barros RS, Assis JB, Silva CCC, Turato WM, Bustia SX, et al. Effects of Long-term low-dose intermittent rapamycin administration on glucose metabolism and immune system of SAMP8 and SAMR1 mice. Front Immunol. 2025;16:1682406.","journal-title":"Front Immunol"},{"issue":"1","key":"2306_CR93","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1111\/acel.12280","volume":"14","author":"EL Goldberg","year":"2015","unstructured":"Goldberg EL, Romero-Aleshire MJ, Renkema KR, Ventevogel MS, Chew WM, Uhrlaub JL, et al. Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms. Aging Cell. 2015;14(1):130\u20138.","journal-title":"Aging Cell"},{"issue":"2","key":"2306_CR94","doi-asserted-by":"publisher","first-page":"757","DOI":"10.4049\/jimmunol.1400188","volume":"193","author":"EL Goldberg","year":"2014","unstructured":"Goldberg EL, Smithey MJ, Lutes LK, Uhrlaub JL, Nikolich-Zugich J. Immune memory-boosting dose of rapamycin impairs macrophage vesicle acidification and curtails glycolysis in effector CD8 cells, impairing defense against acute infections. J Immunol. 2014;193(2):757\u201363.","journal-title":"J Immunol"},{"issue":"268","key":"2306_CR95","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009892","volume":"6","author":"JB Mannick","year":"2014","unstructured":"Mannick JB, Del Giudice G, Lattanzi M, Valiante NM, Praestgaard J, Huang B, et al. mTOR inhibition improves immune function in the elderly. Sci Transl Med. 2014;6(268):268ra179.","journal-title":"Sci Transl Med"},{"key":"2306_CR96","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaq1564","author":"JB Mannick","year":"2018","unstructured":"Mannick JB, Morris M, Hockey HP, Roma G, Beibel M, Kulmatycki K, et al. TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci Transl Med. 2018. https:\/\/doi.org\/10.1126\/scitranslmed.aaq1564.","journal-title":"Sci Transl Med"},{"issue":"5","key":"2306_CR97","doi-asserted-by":"publisher","first-page":"e250","DOI":"10.1016\/S2666-7568(21)00062-3","volume":"2","author":"JB Mannick","year":"2021","unstructured":"Mannick JB, Teo G, Bernardo P, Quinn D, Russell K, Klickstein L, et al. Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials. Lancet Healthy Longev. 2021;2(5):e250\u201362.","journal-title":"Lancet Healthy Longev"},{"issue":"2","key":"2306_CR98","doi-asserted-by":"publisher","DOI":"10.1111\/acel.70364","volume":"25","author":"L Kell","year":"2026","unstructured":"Kell L, Jones EJ, Gharahdaghi N, Wilkinson DJ, Smith K, Atherton PJ, et al. Rapamycin exerts its geroprotective effects in the ageing human immune system by enhancing resilience against DNA damage. Aging Cell. 2026;25(2):e70364.","journal-title":"Aging Cell"},{"issue":"5","key":"2306_CR99","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.1007\/s11357-023-00818-1","volume":"45","author":"TL Kaeberlein","year":"2023","unstructured":"Kaeberlein TL, Green AS, Haddad G, Hudson J, Isman A, Nyquist A, et al. Evaluation of off-label rapamycin use to promote healthspan in 333 adults. Geroscience. 2023;45(5):2757\u201368.","journal-title":"Geroscience"},{"key":"2306_CR100","unstructured":"Green AS. Rapamycin: prevention & treatment of aging and age-related disease 2024 [Available from: https:\/\/rapamycintherapy.com\/."},{"issue":"7404","key":"2306_CR101","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1038\/nature11163","volume":"486","author":"OH Yilmaz","year":"2012","unstructured":"Yilmaz OH, Katajisto P, Lamming DW, Gultekin Y, Bauer-Rowe KE, Sengupta S, et al. mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake. Nature. 2012;486(7404):490\u20135.","journal-title":"Nature"},{"issue":"1","key":"2306_CR102","doi-asserted-by":"publisher","first-page":"6016","DOI":"10.1038\/s41467-025-61070-z","volume":"16","author":"Z Zhang","year":"2025","unstructured":"Zhang Z, Wan Q, Zhu Y, Ye J, Fu F, Fan X, et al. Lipoic acid functions in Paneth cells to prevent human intestinal stem cell aging. Nat Commun. 2025;16(1):6016.","journal-title":"Nat Commun"},{"issue":"3","key":"2306_CR103","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/j.stemcr.2018.01.026","volume":"10","author":"M Yousefi","year":"2018","unstructured":"Yousefi M, Nakauka-Ddamba A, Berry CT, Li N, Schoenberger J, Bankler-Jukes D, et al. Calorie restriction governs intestinal epithelial regeneration through cell-autonomous regulation of mTORC1 in reserve stem cells. Stem cell reports. 2018;10(3):703\u201311.","journal-title":"Stem cell reports"},{"issue":"1","key":"2306_CR104","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/s41467-019-13911-x","volume":"11","author":"D He","year":"2020","unstructured":"He D, Wu H, Xiang J, Ruan X, Peng P, Ruan Y, et al. Gut stem cell aging is driven by mTORC1 via a p38 MAPK-p53 pathway. Nat Commun. 2020;11(1):37.","journal-title":"Nat Commun"},{"issue":"12","key":"2306_CR105","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1038\/s43587-022-00308-7","volume":"2","author":"JC Regan","year":"2022","unstructured":"Regan JC, Lu YX, Urena E, Meilenbrock RL, Catterson JH, Kissler D, et al. Sexual identity of enterocytes regulates autophagy to determine intestinal health, lifespan and responses to rapamycin. Nat Aging. 2022;2(12):1145\u201358.","journal-title":"Nat Aging"},{"issue":"4","key":"2306_CR106","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1111\/j.1474-9726.2012.00832.x","volume":"11","author":"JE Wilkinson","year":"2012","unstructured":"Wilkinson JE, Burmeister L, Brooks SV, Chan CC, Friedline S, Harrison DE, et al. Rapamycin slows aging in mice. Aging Cell. 2012;11(4):675\u201382.","journal-title":"Aging Cell"},{"issue":"1","key":"2306_CR107","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0083988","volume":"9","author":"WC Fok","year":"2014","unstructured":"Fok WC, Chen Y, Bokov A, Zhang Y, Salmon AB, Diaz V, et al. Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome. PLoS One. 2014;9(1):e83988.","journal-title":"PLoS One"},{"issue":"1","key":"2306_CR108","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13059-017-1186-2","volume":"18","author":"T Wang","year":"2017","unstructured":"Wang T, Tsui B, Kreisberg JF, Robertson NA, Gross AM, Yu MK, et al. Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment. Genome Biol. 2017;18(1):57.","journal-title":"Genome Biol"},{"issue":"1","key":"2306_CR109","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s13059-017-1185-3","volume":"18","author":"JJ Cole","year":"2017","unstructured":"Cole JJ, Robertson NA, Rather MI, Thomson JP, McBryan T, Sproul D, et al. Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions. Genome Biol. 2017;18(1):58.","journal-title":"Genome Biol"},{"issue":"9","key":"2306_CR110","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1038\/nm.1851","volume":"14","author":"C Zhang","year":"2008","unstructured":"Zhang C, Cuervo AM. Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat Med. 2008;14(9):959\u201365.","journal-title":"Nat Med"},{"issue":"12","key":"2306_CR111","doi-asserted-by":"publisher","first-page":"8023","DOI":"10.1074\/jbc.M900301200","volume":"284","author":"CC Thoreen","year":"2009","unstructured":"Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, et al. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem. 2009;284(12):8023\u201332.","journal-title":"J Biol Chem"},{"issue":"1","key":"2306_CR112","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1097\/TP.0000000000000476","volume":"99","author":"J Zhu","year":"2015","unstructured":"Zhu J, Lu T, Yue S, Shen X, Gao F, Busuttil RW, et al. Rapamycin protection of livers from ischemia and reperfusion injury is dependent on both autophagy induction and mammalian target of rapamycin complex 2-Akt activation. Transplantation. 2015;99(1):48\u201355.","journal-title":"Transplantation"},{"issue":"6","key":"2306_CR113","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.1016\/j.transproceed.2015.05.013","volume":"47","author":"J Zhu","year":"2015","unstructured":"Zhu J, Hua X, Li D, Zhang J, Xia Q. Rapamycin attenuates mouse liver ischemia and reperfusion injury by inhibiting endoplasmic reticulum stress. Transplant Proc. 2015;47(6):1646\u201352.","journal-title":"Transplant Proc"},{"key":"2306_CR114","doi-asserted-by":"publisher","unstructured":"Taveras C, Cutrone A, Ajenu E, Hassan M, Longchamp A, Tessier S, et al. Preclinical evaluation of mTORC1 inhibition via rapamycin in machine-perfused rodent livers. Res Sq [Preprint]. 2025 Oct 10:rs.3.rs-7340727. [Version 1]. https:\/\/doi.org\/10.21203\/rs.3.rs-7340727\/v1.","DOI":"10.21203\/rs.3.rs-7340727\/v1"},{"issue":"4","key":"2306_CR115","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/j.jaad.2024.08.044","volume":"93","author":"R Wahhab","year":"2025","unstructured":"Wahhab R, Sanders M, Kokikian N, Ni C, Vandiver AR. Clinical consequences of age-related skin barrier dysfunction-Part I: structural, molecular, and physiologic changes with cutaneous aging. J Am Acad Dermatol. 2025;93(4):905\u201314.","journal-title":"J Am Acad Dermatol"},{"issue":"5","key":"2306_CR116","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1111\/ctr.12215","volume":"27","author":"D Ozcan","year":"2013","unstructured":"Ozcan D, Seckin D, Ada S, Haberal M. Mucocutaneous disorders in renal transplant recipients receiving sirolimus-based immunosuppressive therapy: a prospective, case-control study. Clin Transplant. 2013;27(5):742\u20138.","journal-title":"Clin Transplant"},{"issue":"6","key":"2306_CR117","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1007\/s11357-019-00113-y","volume":"41","author":"CL Chung","year":"2019","unstructured":"Chung CL, Lawrence I, Hoffman M, Elgindi D, Nadhan K, Potnis M, et al. Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial. Geroscience. 2019;41(6):861\u20139.","journal-title":"Geroscience"},{"key":"2306_CR118","doi-asserted-by":"publisher","first-page":"1681148","DOI":"10.3389\/fimmu.2025.1681148","volume":"16","author":"J Jia","year":"2025","unstructured":"Jia J, Ma X, Wang T, Ye S, Yan F, Liu J, et al. Yes-associated protein regulates autophagy to restore skin barrier function in atopic dermatitis. Front Immunol. 2025;16:1681148.","journal-title":"Front Immunol"},{"issue":"9S","key":"2306_CR119","doi-asserted-by":"publisher","first-page":"S33","DOI":"10.1097\/DSS.0000000000004805","volume":"51","author":"M Randhawa","year":"2025","unstructured":"Randhawa M, Bojanowski K, Ferraro T, Huang Cao ZF, Day D, Mehta RC. RLX-201, a novel mTORC1 inhibitor with potential to promote skin longevity and cellular health. Dermatol Surg. 2025;51(9S):S33\u20137.","journal-title":"Dermatol Surg"},{"key":"2306_CR120","unstructured":"Garth E. Longevity.Technology 2025 [cited 2025 10\/31\/2025]. Available from: https:\/\/longevity.technology\/news\/mtor-science-has-skin-in-the-game\/."},{"issue":"1","key":"2306_CR121","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1111\/acel.12425","volume":"15","author":"EL Baar","year":"2016","unstructured":"Baar EL, Carbajal KA, Ong IM, Lamming DW. Sex- and tissue-specific changes in mTOR signaling with age in C57BL\/6J mice. Aging Cell. 2016;15(1):155\u201366.","journal-title":"Aging Cell"},{"issue":"1","key":"2306_CR122","doi-asserted-by":"publisher","first-page":"4510","DOI":"10.1038\/s41467-020-18140-1","volume":"11","author":"DJ Ham","year":"2020","unstructured":"Ham DJ, Borsch A, Lin S, Thurkauf M, Weihrauch M, Reinhard JR, et al. The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia. Nat Commun. 2020;11(1):4510.","journal-title":"Nat Commun"},{"key":"2306_CR123","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00141-19","author":"GA Joseph","year":"2019","unstructured":"Joseph GA, Wang SX, Jacobs CE, Zhou W, Kimble GC, Tse HW, et al. Partial inhibition of mTORC1 in aged rats counteracts the decline in muscle mass and reverses molecular signaling associated with sarcopenia. Mol Cell Biol. 2019. https:\/\/doi.org\/10.1128\/MCB.00141-19.","journal-title":"Mol Cell Biol"},{"key":"2306_CR124","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.exger.2015.02.015","volume":"65","author":"MM Markofski","year":"2015","unstructured":"Markofski MM, Dickinson JM, Drummond MJ, Fry CS, Fujita S, Gundermann DM, et al. Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women. Exp Gerontol. 2015;65:1\u20137.","journal-title":"Exp Gerontol"},{"key":"2306_CR125","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.biocel.2016.06.012","volume":"78","author":"Z White","year":"2016","unstructured":"White Z, White RB, McMahon C, Grounds MD, Shavlakadze T. High mTORC1 signaling is maintained, while protein degradation pathways are perturbed in old murine skeletal muscles in the fasted state. Int J Biochem Cell Biol. 2016;78:10\u201321.","journal-title":"Int J Biochem Cell Biol"},{"issue":"23","key":"2306_CR126","doi-asserted-by":"publisher","first-page":"5055","DOI":"10.1113\/JP283686","volume":"600","author":"M Baraldo","year":"2022","unstructured":"Baraldo M, Zorzato S, Dondjang AHT, Geremia A, Nogara L, Dumitras AG, et al. Inducible deletion of raptor and mTOR from adult skeletal muscle impairs muscle contractility and relaxation. J Physiol. 2022;600(23):5055\u201375.","journal-title":"J Physiol"},{"issue":"1","key":"2306_CR127","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1002\/jcsm.12505","volume":"11","author":"AS Ham","year":"2020","unstructured":"Ham AS, Chojnowska K, Tintignac LA, Lin S, Schmidt A, Ham DJ, et al. mTORC1 signalling is not essential for the maintenance of muscle mass and function in adult sedentary mice. J Cachexia Sarcopenia Muscle. 2020;11(1):259\u201373.","journal-title":"J Cachexia Sarcopenia Muscle"},{"issue":"3","key":"2306_CR128","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1002\/jcsm.12412","volume":"10","author":"O Le Bacquer","year":"2019","unstructured":"Le Bacquer O, Combe K, Patrac V, Ingram B, Combaret L, Dardevet D, et al. 4E-BP1 and 4E-BP2 double knockout mice are protected from aging-associated sarcopenia. J Cachexia Sarcopenia Muscle. 2019;10(3):696\u2013709.","journal-title":"J Cachexia Sarcopenia Muscle"},{"issue":"7","key":"2306_CR129","doi-asserted-by":"publisher","first-page":"539","DOI":"10.18632\/aging.100576","volume":"5","author":"L Ye","year":"2013","unstructured":"Ye L, Widlund AL, Sims CA, Lamming DW, Guan Y, Davis JG, et al. Rapamycin doses sufficient to extend lifespan do not compromise muscle mitochondrial content or endurance. Aging (Albany NY). 2013;5(7):539\u201350.","journal-title":"Aging (Albany NY)"},{"issue":"10","key":"2306_CR130","doi-asserted-by":"publisher","DOI":"10.1111\/acel.70183","volume":"24","author":"CJ Elliehausen","year":"2025","unstructured":"Elliehausen CJ, Olszewski SS, Minton DM, Shult CG, Ailiani AR, Trautman ME, et al. Rapamycin Does Not Compromise Exercise-Induced Muscular Adaptations in Female Mice. Aging Cell. 2025;24(10):e70183.","journal-title":"Aging Cell"},{"key":"2306_CR131","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2021.111579","volume":"155","author":"CJ Elliehausen","year":"2021","unstructured":"Elliehausen CJ, Minton DM, Nichol AD, Konopka AR. Skeletal muscle mitochondrial respiration in a model of age-related osteoarthritis is impaired after dietary Rapamycin. Exp Gerontol. 2021;155:111579.","journal-title":"Exp Gerontol"},{"issue":"4","key":"2306_CR132","first-page":"908","volume":"17","author":"M Moel","year":"2025","unstructured":"Moel M, Harinath G, Lee V, Nyquist A, Morgan SL, Isman A, et al. Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results. Aging (Albany NY). 2025;17(4):908\u201336.","journal-title":"Aging (Albany NY)"},{"issue":"7","key":"2306_CR133","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1093\/gerona\/glv307","volume":"71","author":"LW Zaseck","year":"2016","unstructured":"Zaseck LW, Miller RA, Brooks SV. Rapamycin attenuates age-associated changes in tibialis anterior tendon viscoelastic properties. J Gerontol A Biol Sci Med Sci. 2016;71(7):858\u201365.","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"1","key":"2306_CR134","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1186\/s13075-021-02637-1","volume":"23","author":"DM Minton","year":"2021","unstructured":"Minton DM, Elliehausen CJ, Javors MA, Santangelo KS, Konopka AR. Rapamycin-induced hyperglycemia is associated with exacerbated age-related osteoarthritis. Arthritis Res Ther. 2021;23(1):253.","journal-title":"Arthritis Res Ther"},{"key":"2306_CR135","doi-asserted-by":"publisher","unstructured":"Minton DM, Ailiani AR, Focht MDK, Kersh ME, Li A, Elliehausen CJ, et al. Inhibition of mTORC1 by rapamycin results in feedback activation of Akt(S473) and aggravates hallmarks of osteoarthritis in female mice and non-human primates. bioRxiv [Preprint]. 2025 Mar 6:2024.05.14.594256. https:\/\/doi.org\/10.1101\/2024.05.14.594256.","DOI":"10.1101\/2024.05.14.594256"},{"key":"2306_CR136","doi-asserted-by":"publisher","first-page":"3771","DOI":"10.2147\/IJN.S252223","volume":"15","author":"CH Chen","year":"2020","unstructured":"Chen CH, Kuo SM, Tien YC, Shen PC, Kuo YW, Huang HH. Steady augmentation of anti-osteoarthritic actions of rapamycin by liposome-encapsulation in collaboration with low-intensity pulsed ultrasound. Int J Nanomedicine. 2020;15:3771\u201390.","journal-title":"Int J Nanomedicine"},{"issue":"37","key":"2306_CR137","doi-asserted-by":"publisher","first-page":"9904","DOI":"10.1016\/j.biomaterials.2014.08.041","volume":"35","author":"T Matsuzaki","year":"2014","unstructured":"Matsuzaki T, Matsushita T, Tabata Y, Saito T, Matsumoto T, Nagai K, et al. Intra-articular administration of gelatin hydrogels incorporating rapamycin-micelles reduces the development of experimental osteoarthritis in a murine model. Biomaterials. 2014;35(37):9904\u201311.","journal-title":"Biomaterials"},{"issue":"6","key":"2306_CR138","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1186\/s13075-014-0482-4","volume":"16","author":"K Takayama","year":"2014","unstructured":"Takayama K, Kawakami Y, Kobayashi M, Greco N, Cummins JH, Matsushita T, et al. Local intra-articular injection of rapamycin delays articular cartilage degeneration in a murine model of osteoarthritis. Arthritis Res Ther. 2014;16(6):482.","journal-title":"Arthritis Res Ther"},{"issue":"8","key":"2306_CR139","doi-asserted-by":"publisher","first-page":"3272","DOI":"10.1172\/JCI67674","volume":"123","author":"F Neff","year":"2013","unstructured":"Neff F, Flores-Dominguez D, Ryan DP, Horsch M, Schroder S, Adler T, et al. Rapamycin extends murine lifespan but has limited effects on aging. J Clin Invest. 2013;123(8):3272\u201391.","journal-title":"J Clin Invest"},{"issue":"4","key":"2306_CR140","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1007\/s11357-018-0036-9","volume":"40","author":"M Kaeberlein","year":"2018","unstructured":"Kaeberlein M. How healthy is the healthspan concept? Geroscience. 2018;40(4):361\u20134.","journal-title":"Geroscience"},{"key":"2306_CR141","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1093\/bmb\/ldq033","volume":"96","author":"SJ Whitehead","year":"2010","unstructured":"Whitehead SJ, Ali S. Health outcomes in economic evaluation: the QALY and utilities. Br Med Bull. 2010;96:5\u201321.","journal-title":"Br Med Bull"},{"issue":"5","key":"2306_CR142","doi-asserted-by":"publisher","first-page":"4937","DOI":"10.1007\/s11357-024-01226-9","volume":"46","author":"A Luciano","year":"2024","unstructured":"Luciano A, Robinson L, Garland G, Lyons B, Korstanje R, Di Francesco A, et al. Longitudinal fragility phenotyping contributes to the prediction of lifespan and age-associated morbidity in C57BL\/6 and Diversity Outbred mice. Geroscience. 2024;46(5):4937\u201354.","journal-title":"Geroscience"},{"issue":"8034","key":"2306_CR143","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1038\/s41586-024-08026-3","volume":"634","author":"A Di Francesco","year":"2024","unstructured":"Di Francesco A, Deighan AG, Litichevskiy L, Chen Z, Luciano A, Robinson L, et al. Dietary restriction impacts health and lifespan of genetically diverse mice. Nature. 2024;634(8034):684\u201392.","journal-title":"Nature"},{"issue":"4","key":"2306_CR144","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092684","volume":"9","author":"K Makki","year":"2014","unstructured":"Makki K, Taront S, Molendi-Coste O, Bouchaert E, Neve B, Eury E, et al. Beneficial metabolic effects of rapamycin are associated with enhanced regulatory cells in diet-induced obese mice. PLoS One. 2014;9(4):e92684.","journal-title":"PLoS One"},{"issue":"3","key":"2306_CR145","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.cmet.2013.02.008","volume":"17","author":"Y Fang","year":"2013","unstructured":"Fang Y, Westbrook R, Hill C, Boparai RK, Arum O, Spong A, et al. Duration of rapamycin treatment has differential effects on metabolism in mice. Cell Metab. 2013;17(3):456\u201362.","journal-title":"Cell Metab"},{"issue":"4","key":"2306_CR146","doi-asserted-by":"publisher","first-page":"927","DOI":"10.2337\/db15-0502","volume":"65","author":"CM Tran","year":"2016","unstructured":"Tran CM, Mukherjee S, Ye L, Frederick DW, Kissig M, Davis JG, et al. Rapamycin blocks induction of the thermogenic program in white adipose tissue. Diabetes. 2016;65(4):927\u201341.","journal-title":"Diabetes"},{"issue":"4","key":"2306_CR147","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1016\/j.transproceed.2007.04.013","volume":"39","author":"Y Ekici","year":"2007","unstructured":"Ekici Y, Emiroglu R, Ozdemir H, Aldemir D, Karakayali H, Haberal M. Effect of rapamycin on wound healing: an experimental study. Transplant Proc. 2007;39(4):1201\u20133.","journal-title":"Transplant Proc"},{"issue":"10","key":"2306_CR148","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1016\/j.devcel.2024.12.039","volume":"60","author":"G Scepanovic","year":"2025","unstructured":"Scepanovic G, Balaghi N, Rothenberg KE, Fernandez-Gonzalez R. mTor limits autophagy to facilitate cell volume expansion and rapid wound repair in Drosophila embryos. Dev Cell. 2025;60(10):1400-10 e3.","journal-title":"Dev Cell"},{"issue":"4","key":"2306_CR149","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1111\/j.1399-0012.2007.00668.x","volume":"21","author":"RJ Knight","year":"2007","unstructured":"Knight RJ, Villa M, Laskey R, Benavides C, Schoenberg L, Welsh M, et al. Risk factors for impaired wound healing in sirolimus-treated renal transplant recipients. Clin Transplant. 2007;21(4):460\u20135.","journal-title":"Clin Transplant"},{"issue":"2","key":"2306_CR150","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1097\/01.TP.0000072016.13090.4E","volume":"76","author":"C Troppmann","year":"2003","unstructured":"Troppmann C, Pierce JL, Gandhi MM, Gallay BJ, McVicar JP, Perez RV. Higher surgical wound complication rates with sirolimus immunosuppression after kidney transplantation: a matched-pair pilot study. Transplantation. 2003;76(2):426\u20139.","journal-title":"Transplantation"},{"issue":"5","key":"2306_CR151","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010643","volume":"5","author":"CH Squarize","year":"2010","unstructured":"Squarize CH, Castilho RM, Bugge TH, Gutkind JS. Accelerated wound healing by mTOR activation in genetically defined mouse models. PLoS One. 2010;5(5):e10643.","journal-title":"PLoS One"},{"issue":"5","key":"2306_CR152","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1038\/bjp.2008.167","volume":"154","author":"JH Holstein","year":"2008","unstructured":"Holstein JH, Klein M, Garcia P, Histing T, Culemann U, Pizanis A, et al. Rapamycin affects early fracture healing in mice. Br J Pharmacol. 2008;154(5):1055\u201362.","journal-title":"Br J Pharmacol"},{"issue":"4","key":"2306_CR153","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1097\/CAD.0000000000000207","volume":"26","author":"J Trelinska","year":"2015","unstructured":"Trelinska J, Dachowska I, Kotulska K, Fendler W, Jozwiak S, Mlynarski W. Complications of mammalian target of rapamycin inhibitor anticancer treatment among patients with tuberous sclerosis complex are common and occasionally life-threatening. Anticancer Drugs. 2015;26(4):437\u201342.","journal-title":"Anticancer Drugs"},{"key":"2306_CR154","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.exger.2017.12.026","volume":"105","author":"E Kraig","year":"2018","unstructured":"Kraig E, Linehan LA, Liang H, Romo TQ, Liu Q, Wu Y, et al. A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: immunological, physical performance, and cognitive effects. Exp Gerontol. 2018;105:53\u201369.","journal-title":"Exp Gerontol"},{"issue":"1","key":"2306_CR155","doi-asserted-by":"publisher","first-page":"4970","DOI":"10.1038\/s41467-023-40734-8","volume":"14","author":"J Mandrioli","year":"2023","unstructured":"Mandrioli J, D\u2019Amico R, Zucchi E, De Biasi S, Banchelli F, Martinelli I, et al. Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis. Nat Commun. 2023;14(1):4970.","journal-title":"Nat Commun"},{"issue":"2","key":"2306_CR156","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.70274","volume":"17","author":"B Stanfield","year":"2026","unstructured":"Stanfield B, Leroux B, Kaeberlein M, Jones J, Lucas R. Exercise and weekly sirolimus (rapamycin) in older adults: RAPA-EX-01 randomised, double-blind, placebo-controlled trial. J Cachexia Sarcopenia Muscle. 2026;17(2):e70274.","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"2306_CR157","unstructured":"RapAdmin. There are likely about 18,000+ Rapamycin Users in the USA Now Rapamycin News2024 [Available from: https:\/\/www.rapamycin.news\/t\/there-are-likely-about-18-000-rapamycin-users-in-the-usa-now\/16782?utm_source=chatgpt.com."},{"key":"2306_CR158","unstructured":"Johnson B. Blueprint Bryan Johnson [Internet]2025. [cited 2026]. Available from: https:\/\/blueprint.bryanjohnson.com\/blogs\/news\/i-stopped-taking-rapamycin?srsltid=AfmBOopD-r1WJl6TrTtO5kXySJKeqksuZJpL7vZN5xLMdco2cUc6qEQ5."},{"issue":"5","key":"2306_CR159","doi-asserted-by":"publisher","first-page":"2769","DOI":"10.1007\/s11357-023-00935-x","volume":"45","author":"AR Konopka","year":"2023","unstructured":"Konopka AR, Lamming DW, Investigators RP, Investigators E. Blazing a trail for the clinical use of rapamycin as a geroprotecTOR. Geroscience. 2023;45(5):2769\u201383.","journal-title":"Geroscience"},{"key":"2306_CR160","first-page":"2025","volume":"4","author":"SA Repurposed","year":"2025","unstructured":"Repurposed SA, Menopause DMD. Slow Ovarian Aging. NIH. Record. 2025July;4:2025.","journal-title":"Record"},{"key":"2306_CR161","unstructured":"ARPA-H. ARPA-H awards research teams to add more healthy years to Americans\u2019 lives as they age. In: Services USDoHaH, editor. 2026. Available from: https:\/\/arpa-h.gov\/news-and-events\/research-teams-add-more-healthy-years-americans-lives-they-age."},{"key":"2306_CR162","first-page":"2026","volume":"27","author":"S Lee","year":"2026","unstructured":"Lee S. UT San Antonio\u2019s Barshop Institute to receive up to $38M from ARPA-H. UT San Antonio Today. 2026 February 27. Available from: https:\/\/news.utsa.edu\/2026\/02\/ut-san-antonios-barshop-institute-to-receive-up-to-38-million-from-arpa-h\/.","journal-title":"UT San Antonio Today"},{"key":"2306_CR163","unstructured":"UT San Antonio to lead $38 million national trial testing drugs to extend healthspan [press release]. 2026 March 4. Available from: https:\/\/news.uthscsa.edu\/ut-san-antonio-to-lead-38-million-national-trial-testing-drugs-to-extend-healthspan\/."},{"key":"2306_CR164","unstructured":"U of A Launches Rapamycin Clinical Trial with Philanthropic Support of Alumnus Ken Coit [press release]. 2026 April 1. Available from: https:\/\/www.pharmacy.arizona.edu\/news\/2026\/u-launches-rapamycin-clinical-trial-philanthropic-support-alumnus-ken-coit."},{"issue":"12","key":"2306_CR165","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1038\/s43587-024-00744-7","volume":"4","author":"CY Yeh","year":"2024","unstructured":"Yeh CY, Chini LCS, Davidson JW, Garcia GG, Gallagher MS, Freichels IT, et al. Late-life protein or isoleucine restriction impacts physiological and molecular signatures of aging. Nat Aging. 2024;4(12):1760\u201371.","journal-title":"Nat Aging"},{"issue":"11","key":"2306_CR166","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1016\/j.cmet.2023.10.005","volume":"35","author":"CL Green","year":"2023","unstructured":"Green CL, Trautman ME, Chaiyakul K, Jain R, Alam YH, Babygirija R, et al. Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice. Cell Metab. 2023;35(11):1976-95 e6.","journal-title":"Cell Metab"},{"issue":"1","key":"2306_CR167","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29499-8","volume":"13","author":"CM Hill","year":"2022","unstructured":"Hill CM, Albarado DC, Coco LG, Spann RA, Khan MS, Qualls-Creekmore E, et al. FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice. Nat Commun. 2022;13(1):1897.","journal-title":"Nat Commun"},{"issue":"3","key":"2306_CR168","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.cmet.2014.02.009","volume":"19","author":"SM Solon-Biet","year":"2014","unstructured":"Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE, Cogger VC, et al. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab. 2014;19(3):418\u201330.","journal-title":"Cell Metab"},{"issue":"1","key":"2306_CR169","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/s43587-020-00006-2","volume":"1","author":"NE Richardson","year":"2021","unstructured":"Richardson NE, Konon EN, Schuster HS, Mitchell AT, Boyle C, Rodgers AC, et al. Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and lifespan in mice. Nat Aging. 2021;1(1):73\u201386.","journal-title":"Nat Aging"},{"issue":"3","key":"2306_CR170","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.cmet.2017.08.005","volume":"26","author":"MN Roberts","year":"2017","unstructured":"Roberts MN, Wallace MA, Tomilov AA, Zhou Z, Marcotte GR, Tran D, et al. A ketogenic diet extends longevity and healthspan in adult mice. Cell Metab. 2017;26(3):539-46 e5.","journal-title":"Cell Metab"},{"issue":"3","key":"2306_CR171","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1111\/j.1474-9726.2005.00152.x","volume":"4","author":"RA Miller","year":"2005","unstructured":"Miller RA, Buehner G, Chang Y, Harper JM, Sigler R, Smith-Wheelock M. Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell. 2005;4(3):119\u201325.","journal-title":"Aging Cell"},{"issue":"6","key":"2306_CR172","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1038\/s43587-023-00416-y","volume":"3","author":"JB Mannick","year":"2023","unstructured":"Mannick JB, Lamming DW. Targeting the biology of aging with mTOR inhibitors. Nat Aging. 2023;3(6):642\u201360.","journal-title":"Nat Aging"},{"issue":"38","key":"2306_CR173","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2021.707372","volume":"2","author":"SA Fernandes","year":"2021","unstructured":"Fernandes SA, Demetriades C. The multifaceted role of nutrient sensing and mTORC1 signaling in physiology and aging. Front Aging. 2021;2(38):707372.","journal-title":"Front Aging"},{"issue":"5882","key":"2306_CR174","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1126\/science.1157535","volume":"320","author":"Y Sancak","year":"2008","unstructured":"Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science. 2008;320(5882):1496\u2013501.","journal-title":"Science"},{"issue":"8","key":"2306_CR175","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1038\/ncb1753","volume":"10","author":"E Kim","year":"2008","unstructured":"Kim E, Goraksha-Hicks P, Li L, Neufeld TP, Guan KL. Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol. 2008;10(8):935\u201345.","journal-title":"Nat Cell Biol"},{"issue":"1","key":"2306_CR176","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.celrep.2014.09.014","volume":"9","author":"L Chantranupong","year":"2014","unstructured":"Chantranupong L, Wolfson RL, Orozco JM, Saxton RA, Scaria SM, Bar-Peled L, et al. The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell Rep. 2014;9(1):1\u20138.","journal-title":"Cell Rep"},{"issue":"6268","key":"2306_CR177","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1126\/science.aad2087","volume":"351","author":"RA Saxton","year":"2016","unstructured":"Saxton RA, Knockenhauer KE, Wolfson RL, Chantranupong L, Pacold ME, Wang T, et al. Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway. Science. 2016;351(6268):53\u20138.","journal-title":"Science"},{"issue":"6268","key":"2306_CR178","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1126\/science.aab2674","volume":"351","author":"RL Wolfson","year":"2016","unstructured":"Wolfson RL, Chantranupong L, Saxton RA, Shen K, Scaria SM, Cantor JR, et al. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science. 2016;351(6268):43\u20138.","journal-title":"Science"},{"issue":"1","key":"2306_CR179","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.cell.2016.02.035","volume":"165","author":"L Chantranupong","year":"2016","unstructured":"Chantranupong L, Scaria SM, Saxton RA, Gygi MP, Shen K, Wyant GA, et al. The CASTOR proteins are arginine sensors for the mTORC1 pathway. Cell. 2016;165(1):153\u201364.","journal-title":"Cell"},{"issue":"2","key":"2306_CR180","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.cell.2012.02.044","volume":"149","author":"JM Han","year":"2012","unstructured":"Han JM, Jeong SJ, Park MC, Kim G, Kwon NH, Kim HK, et al. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell. 2012;149(2):410\u201324.","journal-title":"Cell"},{"issue":"22","key":"2306_CR181","doi-asserted-by":"publisher","first-page":"10322","DOI":"10.1021\/acs.jmedchem.6b01190","volume":"59","author":"S Yoon","year":"2016","unstructured":"Yoon S, Kim JH, Kim SE, Kim C, Tran PT, Ann J, et al. Discovery of leucyladenylate sulfamates as novel leucyl-tRNA synthetase (LRS)-targeted mammalian target of rapamycin complex 1 (mTORC1) Inhibitors. J Med Chem. 2016;59(22):10322\u20138.","journal-title":"J Med Chem"},{"issue":"15","key":"2306_CR182","doi-asserted-by":"publisher","first-page":"4145","DOI":"10.1016\/j.bmc.2017.06.002","volume":"25","author":"S Yoon","year":"2017","unstructured":"Yoon S, Kim JH, Koh Y, Tran PT, Ann J, Yoon I, et al. Discovery of simplified leucyladenylate sulfamates as novel leucyl-tRNA synthetase (LRS)-targeted mammalian target of rapamycin complex 1 (mTORC1) inhibitors. Bioorg Med Chem. 2017;25(15):4145\u201352.","journal-title":"Bioorg Med Chem"},{"issue":"13","key":"2306_CR183","doi-asserted-by":"publisher","first-page":"3038","DOI":"10.1016\/j.bmcl.2016.05.011","volume":"26","author":"S Yoon","year":"2016","unstructured":"Yoon S, Kim JH, Yoon I, Kim C, Kim SE, Koh Y, et al. Discovery of (S)-4-isobutyloxazolidin-2-one as a novel leucyl-tRNA synthetase (LRS)-targeted mTORC1 inhibitor. Bioorg Med Chem Lett. 2016;26(13):3038\u201341.","journal-title":"Bioorg Med Chem Lett"},{"key":"2306_CR184","doi-asserted-by":"publisher","first-page":"175883591984679","DOI":"10.1177\/1758835919846798","volume":"11","author":"EY Kim","year":"2019","unstructured":"Kim EY, Lee JG, Lee JM, Kim A, Yoo HC, Kim K, et al. Therapeutic effects of the novel Leucyl-tRNA synthetase inhibitor BC-LI-0186 in non-small cell lung cancer. Ther Adv Med Oncol. 2019;11:1758835919846798.","journal-title":"Ther Adv Med Oncol"},{"issue":"1","key":"2306_CR185","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/s41467-018-03035-z","volume":"9","author":"SJ Mahoney","year":"2018","unstructured":"Mahoney SJ, Narayan S, Molz L, Berstler LA, Kang SA, Vlasuk GP, et al. A small molecule inhibitor of Rheb selectively targets mTORC1 signaling. Nat Commun. 2018;9(1):548.","journal-title":"Nat Commun"},{"issue":"3","key":"2306_CR186","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.ccell.2017.01.014","volume":"31","author":"Q Fan","year":"2017","unstructured":"Fan Q, Aksoy O, Wong RA, Ilkhanizadeh S, Novotny CJ, Gustafson WC, et al. A kinase inhibitor targeted to mTORC1 drives regression in glioblastoma. Cancer Cell. 2017;31(3):424\u201335.","journal-title":"Cancer Cell"},{"issue":"1","key":"2306_CR187","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-08345-z","volume":"15","author":"S Mukherjee","year":"2025","unstructured":"Mukherjee S, Wolan MJ, Scott MK, Riley VA, Sokolov AM, Feliciano DM. A bitopic mTORC inhibitor reverses phenotypes in a tuberous sclerosis complex model. Sci Rep. 2025;15(1):20367.","journal-title":"Sci Rep"},{"issue":"1","key":"2306_CR188","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1021\/acs.jmedchem.2c01658","volume":"66","author":"GL Burnett","year":"2023","unstructured":"Burnett GL, Yang YC, Aggen JB, Pitzen J, Gliedt MK, Semko CM, et al. Discovery of RMC-5552, a selective Bi-steric inhibitor of mTORC1, for the treatment of mTORC1-activated tumors. J Med Chem. 2023;66(1):149\u201369.","journal-title":"J Med Chem"},{"issue":"23","key":"2306_CR189","doi-asserted-by":"publisher","first-page":"4933","DOI":"10.1158\/1078-0432.CCR-25-2112","volume":"31","author":"AM Schram","year":"2025","unstructured":"Schram AM, Naqash AR, Haura EB, Riess JW, Ulahannan SV, Ou SI, et al. The Bi-steric, mTORC1-selective inhibitor, RMC-5552, in advanced solid tumors: a phase 1 trial. Clinical cancer research\u202f: an official journal of the American Association for Cancer Research. 2025;31(23):4933\u201343.","journal-title":"Clinical cancer research : an official journal of the American Association for Cancer Research"},{"issue":"1","key":"2306_CR190","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3233\/NHA-180045","volume":"5","author":"DJ Glass","year":"2018","unstructured":"Glass DJ, Lamming DW. Is rapamycin a rapalog? Nutr Healthy Aging. 2018;5(1):21\u20132.","journal-title":"Nutr Healthy Aging"},{"key":"2306_CR191","unstructured":"Sullivan D. New mTOR player storms into longevity2022 10\/12\/2022. Available from: https:\/\/longevity.technology\/news\/new-mtor-player-storms-into-longevity\/."},{"key":"2306_CR192","unstructured":"Mazin A. Lessons from Longevity Therapeutics 2021 \u2013 Part 4 2021 [updated 02\/16\/2021. Available from: https:\/\/www.lifespan.io\/news\/lessons-from-longevity-therapeutics-2021-part-4\/."},{"issue":"4","key":"2306_CR193","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.123.011110","volume":"17","author":"W Wu","year":"2024","unstructured":"Wu W, Jin Q, Ostlund C, Tanji K, Shin JY, Han J, et al. mTOR inhibition prolongs survival and has beneficial effects on heart function after onset of lamin A\/C gene mutation cardiomyopathy in mice. Circ Heart Fail. 2024;17(4):e011110.","journal-title":"Circ Heart Fail"},{"issue":"2","key":"2306_CR194","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1093\/gerona\/glq178","volume":"66","author":"RA Miller","year":"2011","unstructured":"Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R, et al. Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci. 2011;66(2):191\u2013201.","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"24","key":"2306_CR195","doi-asserted-by":"publisher","first-page":"4230","DOI":"10.4161\/cc.10.24.18486","volume":"10","author":"VN Anisimov","year":"2011","unstructured":"Anisimov VN, Zabezhinski MA, Popovich IG, Piskunova TS, Semenchenko AV, Tyndyk ML, et al. Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice. Cell Cycle. 2011;10(24):4230\u20136.","journal-title":"Cell Cycle"},{"issue":"2","key":"2306_CR196","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1093\/gerona\/glt056","volume":"69","author":"Y Zhang","year":"2014","unstructured":"Zhang Y, Bokov A, Gelfond J, Soto V, Ikeno Y, Hubbard G, et al. Rapamycin extends life and health in C57BL\/6 mice. J Gerontol A Biol Sci Med Sci. 2014;69(2):119\u201330.","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"3","key":"2306_CR197","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1111\/acel.12194","volume":"13","author":"RA Miller","year":"2014","unstructured":"Miller RA, Harrison DE, Astle CM, Fernandez E, Flurkey K, Han M, et al. Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Aging Cell. 2014;13(3):468\u201377.","journal-title":"Aging Cell"},{"issue":"11","key":"2306_CR198","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13269","volume":"19","author":"R Strong","year":"2020","unstructured":"Strong R, Miller RA, Bogue M, Fernandez E, Javors MA, Libert S, et al. Rapamycin-mediated mouse lifespan extension: Late-life dosage regimes with sex-specific effects. Aging Cell. 2020;19(11):e13269.","journal-title":"Aging Cell"},{"issue":"1","key":"2306_CR199","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1038\/s41467-020-14962-1","volume":"11","author":"I Ferrara-Romeo","year":"2020","unstructured":"Ferrara-Romeo I, Martinez P, Saraswati S, Whittemore K, Grana-Castro O, Thelma Poluha L, et al. The mTOR pathway is necessary for survival of mice with short telomeres. Nat Commun. 2020;11(1):1168.","journal-title":"Nat Commun"},{"key":"2306_CR200","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2024.101902","volume":"81","author":"M Baghdadi","year":"2024","unstructured":"Baghdadi M, Nespital T, Monzo C, Deelen J, Gronke S, Partridge L. Intermittent rapamycin feeding recapitulates some effects of continuous treatment while maintaining lifespan extension. Mol Metab. 2024;81:101902.","journal-title":"Mol Metab"},{"issue":"7","key":"2306_CR201","doi-asserted-by":"publisher","first-page":"E1495","DOI":"10.1073\/pnas.1717065115","volume":"115","author":"Y Fang","year":"2018","unstructured":"Fang Y, Hill CM, Darcy J, Reyes-Ordonez A, Arauz E, McFadden S, et al. Effects of rapamycin on growth hormone receptor knockout mice. Proc Natl Acad Sci U S A. 2018;115(7):E1495\u2013503.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"2306_CR202","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1111\/acel.12496","volume":"15","author":"R Strong","year":"2016","unstructured":"Strong R, Miller RA, Antebi A, Astle CM, Bogue M, Denzel MS, et al. Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an alpha-glucosidase inhibitor or a Nrf2-inducer. Aging Cell. 2016;15(5):872\u201384.","journal-title":"Aging Cell"},{"key":"2306_CR203","unstructured":"Large rapamycin clinical trial launches at UT Health San Antonio [press release]. UT Health San Antonio. 2026 March 16. Available from: https:\/\/news.uthscsa.edu\/large-rapamycin-clinical-trial-launches-at-ut-health-san-antonio\/."}],"container-title":["GeroScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-026-02306-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11357-026-02306-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-026-02306-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T12:02:29Z","timestamp":1783771349000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11357-026-02306-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":203,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["2306"],"URL":"https:\/\/doi.org\/10.1007\/s11357-026-02306-8","relation":{},"ISSN":["2509-2723"],"issn-type":[{"value":"2509-2723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]},"assertion":[{"value":"2 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"DWL has received funding from, and is a scientific advisory board member of, Aeovian Pharmaceuticals, which seeks to develop novel, selective mTOR inhibitors for the treatment of various diseases.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}