Targeting the biology of aging with mTOR inhibitors
Open accessAbstract
Inhibition of the protein kinase mechanistic target of rapamycin (mTOR) with the Food and Drug Administration (FDA)-approved therapeutic rapamycin promotes health and longevity in diverse model organisms. More recently, specific inhibition of mTORC1 to treat aging-related conditions has become the goal of basic and translational scientists, clinicians and biotechnology companies. Here, we review the effects of rapamycin on the longevity and survival of both wild-type mice and mouse models of human diseases. We discuss recent clinical trials that have explored whether existing mTOR inhibitors can safely prevent, delay or treat multiple diseases of aging. Finally, we discuss how new molecules may provide routes to the safer and more selective inhibition of mTOR complex 1 (mTORC1) in the decade ahead. We conclude by discussing what work remains to be done and the questions that will need to be addressed to make mTOR inhibitors part of the standard of care for diseases of aging.
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The activity of mTOR in the brain increases with age, substantially inhibiting autophagy, which could explain why pathological proteins are prone to accumulation.
“The activity of mTOR in the brain increases with age,117 substantially inhibiting autophagy, which could explain why pathological proteins are prone to accumulation.118”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [117]
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Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351 · see citing works
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227 · see citing works
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766 · see citing works
Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults
Jain, S., Self, W. H., Wunderink, R. G., Fakhran, S. S., BALK, R. A., Bramley, A. M., Reed, C., Grijalva, C. G., Anderson, E. J., Courtney, D. M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500245 · Cited by 3,353 · see citing works
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773 · see citing works
Sarbassov, D. D., Ali, S. M., Kim, D.-H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. M. (2004) · Current Biology · doi:10.1016/j.cub.2004.06.054 · Cited by 2,665 · see citing works
Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB
Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,645 · see citing works
Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for Autophagy
Hosokawa, N., Hara, T., Kaizuka, T., Kishi, C., Takamura, A., Miura, Y., Iemura, S.-I., Natsume, T., Takehana, K., Yamada, N., et al. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-12-1248 · Cited by 2,076 · see citing works
Thoreen, C. C., Kang, S. A., Chang, J. W., Liu, Q., Zhang, J., Gao, Y., Reichling, L. J., Sim, T., Sabatini, D. M., & Gray, N. S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900301200 · Cited by 1,803 · see citing works
Vézina, C., KUDELSKI, A., & Sehgal, S. N. (1975) · The Journal of Antibiotics · doi:10.7164/antibiotics.28.721 · Cited by 1,691 · see citing works
A unifying model for mTORC1-mediated regulation of mRNA translation
Thoreen, C. C., Chantranupong, L., Keys, H. R., Wang, T., Gray, N. S., & Sabatini, D. M. (2012) · Nature · doi:10.1038/nature11083 · Cited by 1,477 · see citing works
Regulation of TORC1 by Rag GTPases in nutrient response
Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P., & Guan, K.-L. (2008) · Nature Cell Biology · doi:10.1038/ncb1753 · Cited by 1,349 · see citing works
Sestrin2 is a leucine sensor for the mTORC1 pathway
Wolfson, R. L., Chantranupong, L., Saxton, R. A., Shen, K., Scaria, S. M., Cantor, J. R., & Sabatini, D. M. (2016) · Science · doi:10.1126/science.aab2674 · Cited by 1,306 · see citing works
Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway
Kapahi, P., Zid, B. M., Harper, T., Koslover, D., Sapin, V., & Benzer, S. (2004) · Current Biology · doi:10.1016/j.cub.2004.03.059 · Cited by 1,293 · see citing works
Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients
Kaeberlein, M., Powers, R. W., Steffen, K. K., Westman, E. A., Hu, D., Dang, N., Kerr, E. O., Kirkland, K. T., Fields, S., & Kennedy, B. K. (2005) · Science · doi:10.1126/science.1115535 · Cited by 1,293 · see citing works
Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells
Yilmaz, Ö. H., Valdez, R., Theisen, B. K., Guo, W., Ferguson, D. O., Wu, H., & Morrison, S. J. (2006) · Nature · doi:10.1038/nature04703 · Cited by 1,272 · see citing works
Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity
Lamming, D. W., Ye, L., Katajisto, P., Goncalves, M. D., Saitoh, M., Stevens, D. M., Davis, J. G., Salmon, A. B., Richardson, A., Ahima, R. S., et al. (2012) · Science · doi:10.1126/science.1215135 · Cited by 1,199 · see citing works
Self-citationRibosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span
Selman, C., Tullet, J. M. A., Wieser, D., Irvine, E., Lingard, S. J., Choudhury, A. I., Claret, M., Al-Qassab, H., Carmignac, D., Ramadani, F., et al. (2009) · Science · doi:10.1126/science.1177221 · Cited by 1,120 · see citing works
Bar-Peled, L., Chantranupong, L., Cherniack, A. D., Chen, W. W., Ottina, K. A., Grabiner, B. C., Spear, E. D., Carter, S. L., Meyerson, M., & Sabatini, D. M. (2013) · Science · doi:10.1126/science.1232044 · Cited by 1,080 · cited 1× · see citing works
“167 ,168).”
Influence of TOR kinase on lifespan in C. elegans
Vellai, T., Takacs-Vellai, K., Zhang, Y., Kovacs, A. L., Orosz, L., & Müller, F. (2003) · Nature · doi:10.1038/426620a · Cited by 1,057 · see citing works
Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila Melanogaster
Bjedov, I., Toivonen, J. M., Kerr, F., Slack, C., Jacobson, J., Foley, A., & Partridge, L. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2009.11.010 · Cited by 1,057 · see citing works
Spilman, P., Podlutskaya, N., Hart, M. J., Debnath, J., Gorostiza, O., Bredesen, D., Richardson, A., Strong, R., & Galvan, V. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009979 · Cited by 1,033 · see citing works
Rheb Binds and Regulates the mTOR Kinase
Long, X., Lin, Y., Ortiz-Vega, S., Yonezawa, K., & Avruch, J. (2005) · Current Biology · doi:10.1016/j.cub.2005.02.053 · Cited by 1,005 · see citing works
Extension of Chronological Life Span in Yeast by Decreased TOR Pathway Signaling
Powers, R. W., Kaeberlein, M., Caldwell, S. D., Kennedy, B. K., & Fields, S. (2006) · Genes & Development · doi:10.1101/gad.1381406 · Cited by 982 · see citing works
An aged immune system drives senescence and ageing of solid organs
Yousefzadeh, M. J., Flores, R. R., Zhu, Y., Schmiechen, Z. C., Brooks, R. W., Trussoni, C. E., Cui, Y., Angelini, L., Lee, K.-A., McGowan, S. J., et al. (2021) · Nature · doi:10.1038/s41586-021-03547-7 · Cited by 972 · cited 1× · see citing works
“Premature aging of the immune system has been shown to drive aging of multiple other organ systems in mice 81 .”
THE MAINTENANCE OF THE ACCURACY OF PROTEIN SYNTHESIS AND ITS RELEVANCE TO AGEING
Orgel, L. E. (1963) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.49.4.517 · Cited by 968 · see citing works
Rapamycin suppresses 5′TOP mRNA translation through inhibition of p70s6k
Jefferies, H. B. J., Fumagalli, S., Dennis, P. B., Reinhard, C., Pearson, R. B., & Thomas, G. (1997) · The EMBO Journal · doi:10.1093/emboj/16.12.3693 · Cited by 934 · see citing works
Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans
Hansen, M., Taubert, S., Crawford, D., Libina, N., Lee, S.-J., & Kenyon, C. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2006.00267.x · Cited by 918 · see citing works
Solon-Biet, S. M., McMahon, A. C., Ballard, J. W. O., Ruohonen, K., Wu, L. E., Cogger, V. C., Warren, A., Huang, X., Pichaud, N., Melvin, R. G., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.02.009 · Cited by 904 · see citing works
Rapamycin, But Not Resveratrol or Simvastatin, Extends Life Span of Genetically Heterogeneous Mice
Miller, R. A., Harrison, D. E., Astle, C. M., Baur, J. A., Boyd, A. R., de Cabo, R., Fernandez, E., Flurkey, K., Javors, M. A., Nelson, J. F., et al. (2011) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glq178 · Cited by 896 · see citing works
Jang, Y.-Y., & Sharkis, S. J. (2007) · Blood · doi:10.1182/blood-2007-05-087759 · Cited by 894 · see citing works
Molecular Interplay between Mammalian Target of Rapamycin (mTOR), Amyloid-β, and Tau
Caccamo, A., Majumder, S., Richardson, A., Strong, R., & Oddo, S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.100420 · Cited by 881 · see citing works
Brandhorst, S., Choi, I. Y., Wei, M., Cheng, C. W., Sedrakyan, S., Navarrete, G., Dubeau, L., Yap, L. P., Park, R., Vinciguerra, M., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.012 · Cited by 850 · see citing works
The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway
Chantranupong, L., Scaria, S. M., Saxton, R. A., Gygi, M. P., Shen, K., Wyant, G. A., Wang, T., Harper, J. W., Gygi, S. P., & Sabatini, D. M. (2016) · Cell · doi:10.1016/j.cell.2016.02.035 · Cited by 843 · see citing works
Regulation of Immune Responses by mTOR
Powell, J. D., Pollizzi, K. N., Heikamp, E. B., & Horton, M. R. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075024 · Cited by 836 · see citing works
Leucyl-tRNA Synthetase Is an Intracellular Leucine Sensor for the mTORC1-Signaling Pathway
Han, J. M., Jeong, S. J., Park, M. C., Kim, G., Kwon, N. H., Kim, H. K., Ha, S. H., Ryu, S. H., & Kim, S. (2012) · Cell · doi:10.1016/j.cell.2012.02.044 · Cited by 824 · see citing works
Autophagy and aging: The importance of maintaining "clean" cells
Cuervo, A. M., Bergamini, E., Brunk, U. T., Dröge, W., Ffrench, M., & Terman, A. (2005) · Autophagy · doi:10.4161/auto.1.3.2017 · Cited by 792 · see citing works
Menon, S., Dibble, C. C., Talbott, G., Hoxhaj, G., Valvezan, A., Takahashi, H., Cantley, L., & Manning, B. (2014) · Cell · doi:10.1016/j.cell.2013.11.049 · Cited by 787 · see citing works
mTOR inhibition improves immune function in the elderly
Mannick, J. B., Del Giudice, G., Lattanzi, M., Valiante, N. M., Praestgaard, J., Huang, B., Lonetto, M. A., Maecker, H. T., Kovarik, J., Carson, S., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009892 · Cited by 786 · see citing works
Self-citationKim, K. H., Jeong, Y. T., Oh, H., Kim, S. H., Cho, J. M., Kim, Y.-N., Kim, S. S., Kim, D. H., Hur, K. Y., Kim, H. K., et al. (2013) · Nature Medicine · doi:10.1038/nm.3014 · Cited by 774 · see citing works
A Role for Autophagy in the Extension of Lifespan by Dietary Restriction in C. elegans
Hansen, M., Chandra, A., Mitic, L. L., Onken, B., Driscoll, M., & Kenyon, C. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.0040024 · Cited by 766 · see citing works
mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake
Yilmaz, Ö. H., Katajisto, P., Lamming, D. W., Gültekin, Y., Bauer-Rowe, K. E., Sengupta, S., Birsoy, K., Dursun, A., Yilmaz, V. O., Selig, M., et al. (2012) · Nature · doi:10.1038/nature11163 · Cited by 753 · see citing works
Self-citationMiller, R. A., Buehner, G., Chang, Y., Harper, J. M., Sigler, R. E., & Smith‐Wheelock, M. (2005) · Aging Cell · doi:10.1111/j.1474-9726.2005.00152.x · Cited by 734 · see citing works
ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS
Alexander, A., Cai, S.-L., Kim, J., Nanez, A., Sahin, M., MacLean, K. H., Inoki, K., Guan, K.-L., Shen, J., Person, M. D., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913860107 · Cited by 717 · see citing works
Wilkinson, J. E., Burmeister, L., Brooks, S. V., Chan, C., Friedline, S., Harrison, D. E., Hejtmancik, J. F., Nadon, N. L., Strong, R., Wood, L. K., et al. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00832.x · Cited by 682 · see citing works
mTOR Regulation and Therapeutic Rejuvenation of Aging Hematopoietic Stem Cells
Chen, C., Liu, Y., Liu, Y., & Zheng, P. (2009) · Science Signaling · doi:10.1126/scisignal.2000559 · Cited by 680 · see citing works
TOR Signaling and Rapamycin Influence Longevity by Regulating SKN-1/Nrf and DAF-16/FoxO
Robida-Stubbs, S., Glover-Cutter, K., Lamming, D. W., Mizunuma, M., Narasimhan, S. D., Neumann-Haefelin, E., Sabatini, D. M., & Blackwell, T. K. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.007 · Cited by 648 · see citing works
Self-citationKume, S., Uzu, T., Horiike, K., Chin-Kanasaki, M., Isshiki, K., Araki, S.-I., Sugimoto, T., Haneda, M., Kashiwagi, A., & Koya, D. (2010) · Journal of Clinical Investigation · doi:10.1172/jci41376 · Cited by 640 · see citing works
Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex.
Zeng, L., Xu, L., Gutmann, D. H., & Wong, M. (2008) · Annals of Neurology · doi:10.1002/ana.21331 · Cited by 639 · see citing works
Miller, R. A., Harrison, D. E., Astle, C. M., Fernández, E., Flurkey, K., Han, M. L., Javors, M. A., Li, X., Nadon, N. L., Nelson, J. F., et al. (2013) · Aging Cell · doi:10.1111/acel.12194 · Cited by 624 · see citing works
mTOR Is Essential for Growth and Proliferation in Early Mouse Embryos and Embryonic Stem Cells
Murakami, M., Ichisaka, T., Maeda, M., Oshiro, N., Hara, K., Edenhofer, F., Kiyama, H., Yonezawa, K., & Yamanaka, S. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.15.6710-6718.2004 · Cited by 620 · see citing works
Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells
Sadtler, K., Estrellas, K., Allen, B. W., Wolf, M. T., Fan, H., Tam, A. J., Patel, C. H., Luber, B. S., Wang, H., Wagner, K. R., et al. (2016) · Science · doi:10.1126/science.aad9272 · Cited by 605 · see citing works
Tsun, Z.-Y., Bar-Peled, L., Chantranupong, L., Zoncu, R., Wang, T., Kim, C., Spooner, E., & Sabatini, D. M. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.09.016 · Cited by 565 · see citing works
Lysosomal cholesterol activates mTORC1 via an SLC38A9–Niemann-Pick C1 signaling complex
Castellano, B. M., Thelen, A. M., Moldavski, O., Feltes, M., van der Welle, R. E. N., Mydock-McGrane, L., Jiang, X., van Eijkeren, R. J., Davis, O. B., Louie, S. M., et al. (2017) · Science · doi:10.1126/science.aag1417 · Cited by 562 · see citing works
Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40
Yang, H., Jiang, X., Li, B., Yang, H. J., Miller, M., Yang, A., Dhar, A., & Pavletich, N. P. (2017) · Nature · doi:10.1038/nature25023 · Cited by 548 · see citing works
Tabernero, J. M., Rojo, F., Calvo, E., Burris, H. A., Judson, I. R., Hazell, K., Martinelli, E., y Cajal, S. R., Jones, S. F., Vidal, L., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.5482 · Cited by 537 · see citing works
Rapalogs and mTOR inhibitors as anti-aging therapeutics
Lamming, D. W., Ye, L., Sabatini, D. M., & Baur, J. A. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64099 · Cited by 531 · see citing works
Self-citationThe metabolic footprint of aging in mice
Houtkooper, R. H., Argmann, C., Houten, S. M., Cantó, C., Jeninga, E. H., Andreux, P. A., Thomas, C., Doenlen, R., Schoonjans, K., & Auwerx, J. (2011) · Scientific Reports · doi:10.1038/srep00134 · Cited by 528 · see citing works
Zhang, C., & Cuervo, A. M. (2008) · Nature Medicine · doi:10.1038/nm.1851 · Cited by 520 · see citing works
mTOR Inhibition Alleviates Mitochondrial Disease in a Mouse Model of Leigh Syndrome
Johnson, S. C., Yanos, M. E., Kayser, E., Quintana, A., Sangesland, M., Castanza, A. S., Uhde, L., Hui, J., Wall, V., Gagnidze, A., et al. (2013) · Science · doi:10.1126/science.1244360 · Cited by 520 · see citing works
A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice
Roberts, M. N., Wallace, M. A., Tomilov, A. A., Zhou, Z., Marcotte, G. R., Tran, D., Perez, G., Gutierrez-Casado, E., Koike, S., Knotts, T. A., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.005 · Cited by 514 · see citing works
TORC1 inhibition enhances immune function and reduces infections in the elderly
Mannick, J. B., Morris, M., Hockey, H.-U. P., Roma, G., Beibel, M., Kulmatycki, K., Watkins, M., Shavlakadze, T., Zhou, W., Quinn, D., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aaq1564 · Cited by 496 · see citing works
Self-citationTransient rapamycin treatment can increase lifespan and healthspan in middle-aged mice
Bitto, A., Ito, T. K., Pineda, V. V., LeTexier, N. J., Huang, H. Z., Sutlief, E., Tung, H., Vizzini, N., Chen, B., Smith, K., et al. (2016) · eLife · doi:10.7554/elife.16351 · Cited by 474 · see citing works
Yeast Life Span Extension by Depletion of 60S Ribosomal Subunits Is Mediated by Gcn4
Steffen, K. K., MacKay, V. L., Kerr, E. O., Tsuchiya, M., Hu, D., Fox, L. A., Dang, N., Johnston, E. D., Oakes, J. A., Tchao, B. N., et al. (2008) · Cell · doi:10.1016/j.cell.2008.02.037 · Cited by 465 · see citing works
Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway
Saxton, R. A., Knockenhauer, K. E., Wolfson, R. L., Chantranupong, L., Pacold, M. E., Wang, T., Schwartz, T. U., & Sabatini, D. M. (2016) · Science · doi:10.1126/science.aad2087 · Cited by 457 · see citing works
Sirolimus Is Associated with New-Onset Diabetes in Kidney Transplant Recipients
Johnston, O., Rose, C., Webster, A. C., & Gill, J. S. (2008) · Journal of the American Society of Nephrology · doi:10.1681/asn.2007111202 · Cited by 425 · see citing works
Structure of the Human mTOR Complex I and Its Implications for Rapamycin Inhibition
Yip, C. K., Murata, K., Walz, T., Sabatini, D. M., & Kang, S. A. W. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.017 · Cited by 413 · see citing works
Rictor/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegansPreprint
Soukas, A. A., Kane, E., Carr, C. E., Melo, J. A. T., & Ruvkun, G. (2009) · Genes & Development · doi:10.1101/gad.1775409 · Cited by 410 · see citing works
mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice
Guertin, D. A., Stevens, D. M., Saitoh, M., Kinkel, S., Crosby, K., Sheen, J.-H., Mullholland, D. J., Magnuson, M. A., Wu, H., & Sabatini, D. M. (2009) · Cancer Cell · doi:10.1016/j.ccr.2008.12.017 · Cited by 402 · see citing works
Majumder, S., Richardson, A. G., Strong, R., & Oddo, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025416 · Cited by 401 · see citing works
Rapamycin extends murine lifespan but has limited effects on aging
Neff, F., Flores-Dominguez, D., Ryan, D. P., Horsch, M., Schröder, S., Adler, T., Afonso, L. C., Aguilar-Pimentel, J. A., Becker, L., Garrett, L., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67674 · Cited by 374 · see citing works
Zhang, X., Li, L., Chen, S., Yang, D., Wang, Y., Zhang, X., Wang, Z., & Le, W. (2011) · Autophagy · doi:10.4161/auto.7.4.14541 · Cited by 364 · see citing works
Strong, R., Miller, R. A., Antebi, A., Astle, C. M., Bogue, M., Denzel, M. S., Fernandez, E., Flurkey, K., Hamilton, K. L., Lamming, D. W., et al. (2016) · Aging Cell · doi:10.1111/acel.12496 · Cited by 362 · see citing works
Self-citationDeelen, J., Kettunen, J., Fischer, K., van der Spek, A., Trompet, S., Kastenmüller, G., Boyd, A., Zierer, J., van den Akker, E. B., Ala-Korpela, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11311-9 · Cited by 362 · see citing works
eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans
Syntichaki, P., Troulinaki, K., & Tavernarakis, N. (2007) · Nature · doi:10.1038/nature05603 · Cited by 361 · see citing works
Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism
Wang, R., Yu, Z., Sunchu, B., Shoaf, J., Dang, I., Zhao, S., Caples, K., Bradley, L., Beaver, L. M., Ho, E., et al. (2017) · Aging Cell · doi:10.1111/acel.12587 · Cited by 360 · see citing works
Ramos, F. J., Chen, S. C., Garelick, M. G., Dai, D.-F., Liao, C.-Y., Schreiber, K. H., MacKay, V. L., An, E. H., Strong, R., Ladiges, W. C., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003802 · Cited by 349 · see citing works
Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice
Anisimov, V. N., Zabezhinski, M. A., Popovich, I. G., Piskunova, T. S., Semenchenko, A. V., Тындык, М. Л., Yurova, M. N., Rosenfeld, S. V., & Blagosklonny, M. V. (2011) · Cell Cycle · doi:10.4161/cc.10.24.18486 · Cited by 347 · see citing works
Tramutola, A., Triplett, J. C., Di Domenico, F., Niedowicz, D. M., Murphy, M. P., Coccia, R., Perluigi, M., & Butterfield, D. A. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13037 · Cited by 347 · see citing works
Architecture of human mTOR complex 1
Aylett, C. H. S., Sauer, E., Imseng, S., Boehringer, D., Hall, M. N., Ban, N., & Maier, T. (2016) · Science · doi:10.1126/science.aaa3870 · Cited by 344 · see citing works
New functions of aminoacyl-tRNA synthetases beyond translation
Guo, M., Yang, X., & SCHIMMEL, P. R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2956 · Cited by 333 · see citing works
Wu, J., Liu, J., Chen, E. B., Wang, J., Cao, L., Narayan, N., Fergusson, M. M., Rovira, I. I., Allen, M. D., Springer, D., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.07.030 · Cited by 328 · see citing works
Dai, D., Karunadharma, P. P., Chiao, Y. A., Basisty, N., Crispin, D. A., Hsieh, E. J., Chen, T., Gu, H., Djukovic, D., Raftery, D., et al. (2014) · Aging Cell · doi:10.1111/acel.12203 · Cited by 328 · see citing works
An, W.-L., Cowburn, R. F., Li, L., Braak, H., Alafuzoff, I., Iqbal, K., Iqbal, I.-G., Winblad, B., & Pei, J.-J. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63687-5 · Cited by 312 · see citing works
Late-life rapamycin treatment reverses age-related heart dysfunction
Flynn, J. M., O’Leary, M. N., Zambataro, C. A., Academia, E. C., Presley, M. P., Garrett, B., Zykovich, A., Mooney, S. D., Strong, R., Rosen, C. J., et al. (2013) · Aging Cell · doi:10.1111/acel.12109 · Cited by 311 · see citing works
Medvedik, O., Lamming, D. W., Kim, K. D., & Sinclair, D. A. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050261 · Cited by 311 · see citing works
Self-citationMechanism of arginine sensing by CASTOR1 upstream of mTORC1
Saxton, R., Chantranupong, L., Knockenhauer, K., Schwartz, T., & Sabatini, D. (2016) · Nature · doi:10.1038/nature19079 · Cited by 301 · see citing works
The Emerging Roles of mTORC1 in Macromanaging Autophagy
Dossou, A. S., & Basu, A. (2019) · Cancers · doi:10.3390/cancers11101422 · Cited by 292 · see citing works
Panchaud, N., Gulli, M., & VIRGILIO, C. D. (2013) · Science Signaling · doi:10.1126/scisignal.2004112 · Cited by 290 · see citing works
Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia
Maude, S. L., Tasian, S. K., Vincent, T. L., Hall, J., Sheen, C., Roberts, K. G., Seif, A. E., Barrett, D. M., Chen, I., Collins, J. R., et al. (2012) · Blood · doi:10.1182/blood-2012-03-415448 · Cited by 288 · see citing works
The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas
Hernando, E., Charytonowicz, E., Dudas, M. E., Menéndez, S., Matushansky, I., Mills, J. E., Socci, N. D., Behrendt, N., Ma, L., Maki, R. G., et al. (2007) · Nature Medicine · doi:10.1038/nm1560 · Cited by 288 · see citing works
Rapamycin Extends Life and Health in C57BL/6 Mice
Zhang, Y., Bokov, A. F., Gelfond, J., Soto, V., Ikeno, Y., Hubbard, G. B., Diaz, V., Sloane, L. B., Maslin, K., Treaster, S. B., et al. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt056 · Cited by 276 · see citing works
Richardson, N. E., Konon, E. N., Schuster, H. S., Mitchell, A. T., Boyle, C., Rodgers, A. C., Finke, M., Haider, L. R., Yu, D., Flores, V., et al. (2021) · Nature Aging · doi:10.1038/s43587-020-00006-2 · Cited by 264 · see citing works
Self-citationRapamycin Extends Maximal Lifespan in Cancer-Prone Mice
Anisimov, V. N., Zabezhinski, M. A., Popovich, I. G., Piskunova, T. S., Semenchenko, A. V., Тындык, М. Л., Yurova, M. N., Antoch, M. P., & Blagosklonny, M. V. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.091050 · Cited by 257 · see citing works
Activating transcription factor 4-dependent induction of FGF21 during amino acid deprivation
De Sousa-Coelho, A. L., Marrero, P. F., & Haro, D. (2012) · Biochemical Journal · doi:10.1042/bj20111748 · Cited by 246 · see citing works
Dihydroxyacetone phosphate signals glucose availability to mTORC1
Orozco, J. M., Krawczyk, P. A., Scaria, S. M., Cangelosi, A. L., Chan, S. H., Kunchok, T., Lewis, C. A., & Sabatini, D. M. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0250-5 · Cited by 245 · see citing works
Park, Y., Reyna‐Neyra, A., Philippe, L., & Thoreen, C. C. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.04.042 · Cited by 242 · see citing works
Autophagy Regulates Ageing in<i>C. elegans</i>
Hars, E. S., Qi, H., Jin, S. V., Cai, L., Hu, C., & Liu, L. F. (2007) · Autophagy · doi:10.4161/auto.3636 · Cited by 238 · see citing works
Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island
Apelo, S. I. A., & Lamming, D. W. (2016) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw090 · Cited by 238 · see citing works
Self-citationChung, C. L., Lawrence, I., Hoffman, M. L., Elgindi, D., Nadhan, K. S., Potnis, M., Jin, A., Sershon, C., Binnebose, R., Lorenzini, A., et al. (2019) · GeroScience · doi:10.1007/s11357-019-00113-y · Cited by 226 · see citing works
Halloran, J. J., Hussong, S. A., Burbank, R. R., Podlutskaya, N., Fischer, K. E., Sloane, L. B., Austad, S. N., Strong, R., Richardson, A. G., Hart, M. J., et al. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.06.054 · Cited by 221 · see citing works
BMAL1-dependent regulation of the mTOR signaling pathway delays aging
Khapre, R. V., Kondratova, A. A., Patel, S. A., Dubrovsky, Y. V., Wrobel, M. M., Antoch, M. P., & Kondratov, R. V. (2014) · Aging · doi:10.18632/aging.100633 · Cited by 215 · see citing works
Autophagy is required for extension of yeast chronological life span by rapamycin
Alvers, A. L., Wood, M. S., Hu, D., Kaywell, A. C., Dunn, W. A., & Aris, J. P. (2009) · Autophagy · doi:10.4161/auto.8824 · Cited by 212 · see citing works
Zhou, J., Su, P., Wang, L., Chen, J., Zimmermann, M., Genbačev, O., Afonja, O., Horne, M. C., Tanaka, T. S., Duan, E., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0901854106 · Cited by 205 · see citing works
Hua, Y., Zhang, Y., Ceylan‐Isik, A. F., Wold, L. E., Nunn, J. M., & Ren, J. T. (2011) · Basic Research in Cardiology · doi:10.1007/s00395-011-0222-8 · Cited by 204 · see citing works
A novel rapamycin analog is highly selective for mTORC1 in vivo
Schreiber, K. H., Apelo, S. I. A., Yu, D., Brinkman, J. A., Velarde, M. C., Syed, F. A., Liao, C., Baar, E. L., Carbajal, K. A., Sherman, D. S., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11174-0 · Cited by 194 · see citing works
Self-citationArchitecture of the human GATOR1 and GATOR1–Rag GTPases complexes
Shen, K., Huang, R. K., Brignole, E. J., Condon, K. J., Valenstein, M. L., Chantranupong, L., Bomaliyamu, A., Choe, A., Hong, C., Yu, Z., et al. (2018) · Nature · doi:10.1038/nature26158 · Cited by 192 · see citing works
Structural basis for the docking of mTORC1 on the lysosomal surface
Rogala, K. B., Gu, X., Kedir, J. F., Abu-Remaileh, M., Bianchi, L. F., Bottino, A. M. S., Dueholm, R., Niehaus, A., Overwijn, D., Fils, A.-C. P., et al. (2019) · Science · doi:10.1126/science.aay0166 · Cited by 191 · see citing works
A Kinase Inhibitor Targeted to mTORC1 Drives Regression in Glioblastoma
Fan, Q.-W., Aksoy, O., Wong, R. A., Ilkhanizadeh, S., Novotny, C. J., Gustafson, W. C., Truong, A. Y.-Q., Cayanan, G., Simonds, E. F., Haas-Kogan, D. A., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.01.014 · Cited by 184 · see citing works
Lysosome: The metabolic signaling hub
Lamming, D. W., & Bar‐Peled, L. (2018) · Traffic · doi:10.1111/tra.12617 · Cited by 183 · see citing works
Self-citationArriola Apelo, S. I., Neuman, J. C., Baar, E. L., Syed, F. A., Cummings, N. E., Brar, H. K., Pumper, C. P., Kimple, M. E., & Lamming, D. W. (2016) · Aging Cell · doi:10.1111/acel.12405 · Cited by 182 · see citing works
Self-citationWarner, L. M., Adams, L. M., & Sehgal, S. N. (1994) · Arthritis & Rheumatism · doi:10.1002/art.1780370219 · Cited by 180 · see citing works
The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia
Ham, D. J., Börsch, A., Lin, S., Thürkauf, M., Weihrauch, M., Reinhard, J. R., Delezie, J., Battilana, F., Wang, X., Kaiser, M. S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18140-1 · Cited by 178 · see citing works
Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity
Carroll, B., Maetzel, D., Maddocks, O., Otten, G., Ratcliff, M., Smith, G. R., Dunlop, E., Passos, J., Davies, O. R., Jaenisch, R., et al. (2016) · eLife · doi:10.7554/elife.11058 · Cited by 177 · see citing works
Huyghe, É., Zairi, A., Nohra, J., Kamar, N., Plante, P., & Rostaing, L. P. E. (2006) · Transplant International · doi:10.1111/j.1432-2277.2006.00423.x · Cited by 172 · see citing works
Sex‐ and tissue‐specific changes in mTOR signaling with age in C57BL/6J mice
Baar, E. L., Carbajal, K. A., Ong, I., & Lamming, D. (2015) · Aging Cell · doi:10.1111/acel.12425 · Cited by 170 · see citing works
Self-citationSirolimus May Reduce Fertility in Male Renal Transplant Recipients
Zuber, J., Anglicheau, D., Elie, C., Bererhi, L., Timsit, M., Mamzer, M., Ciroldi, M., Martinez, F., Snanoudj, R., HIESSE, C., et al. (2008) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2008.02267.x · Cited by 169 · see citing works
Bissler, J. J., Kingswood, J. C., Radzikowska, E., Zonnenberg, B. A., Белоусова, Е. Д., Frost, M., Sauter, M., Brakemeier, S., de Vries, P. J., Berkowitz, N. C., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0180939 · Cited by 168 · see citing works
Kraig, E., Linehan, L. A., Liang, H., Romo, T. Q., Liu, Q., Wu, Y., Benavides, A. D., Curiel, T. J., Javors, M. A., Musi, N., et al. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2017.12.026 · Cited by 168 · see citing works
Urfer, S. R., Kaeberlein, T. L., Mailheau, S., Bergman, P. J., Creevy, K. E., Promislow, D., & Kaeberlein, M. R. (2017) · GeroScience · doi:10.1007/s11357-017-9972-z · Cited by 167 · see citing works
Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice
Mao, K., Quipildor, G. F., Tabrizian, T., Novaj, A., Guan, F., Walters, R. O., Delahaye, F., Hubbard, G. B., Ikeno, Y., Ejima, K., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04805-5 · Cited by 167 · see citing works
Lee, K.-W., Yook, J.-Y., Son, M., Kim, M., Koo, D., Han, Y., & Cho, Y. S. (2009) · Stem Cells and Development · doi:10.1089/scd.2009.0147 · Cited by 163 · see citing works
The central moTOR of metabolism
Simcox, J., & Lamming, D. W. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.02.024 · Cited by 163 · see citing works
Self-citationJoseph, G. A., Wang, S. X., Jacobs, C. E., Zhou, W., Kimble, G. C., Tse, H. W., Eash, J. K., Shavlakadze, T., & Glass, D. J. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00141-19 · Cited by 161 · see citing works
Markofski, M., Dickinson, J., Drummond, M., Fry, C., Fujita, S., Gundermann, D., Glynn, E., Jennings, K., Paddon-Jones, D., Reidy, P., et al. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.02.015 · Cited by 155 · see citing works
Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain
Perluigi, M., Pupo, G., Tramutola, A., Cini, C., Coccia, R., Barone, E., Head, E., Butterfield, D. A., & Di Domenico, F. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.04.007 · Cited by 155 · see citing works
Lin, A., Jahrling, J. B., Zhang, W., DeRosa, N., Bakshi, V., Romero, P., Galván, V., & Richardson, A. G. (2015) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x15621575 · Cited by 154 · see citing works
Long-term treatment of epilepsy with everolimus in tuberous sclerosis
Krueger, D. A., Wilfong, A. A., Mays, M., Talley, C., Agricola, K. D., Tudor, C., Capal, J. K., Holland‐Bouley, K. D., & Franz, D. N. (2016) · Neurology · doi:10.1212/wnl.0000000000003400 · Cited by 154 · see citing works
An open science study of ageing in companion dogs
Creevy, K. E., Akey, J. M., Kaeberlein, M. R., Promislow, D., Barnett, B. G., Benton, B., Borenstein, E., Castelhano, M. G., Chou, L., Collins, D., et al. (2022) · Nature · doi:10.1038/s41586-021-04282-9 · Cited by 151 · see citing works
Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/− mice
Komarova, E. A., Antoch, M. P., Novototskaya, L. R., Chernova, O. B., Paszkiewicz, G., Leontieva, O. V., Blagosklonny, M. V., & Gudkov, A. V. (2012) · Aging · doi:10.18632/aging.100498 · Cited by 145 · see citing works
Fok, W. C., Chen, Y., Bokov, A. F., Zhang, Y., Salmon, A. B., Diaz, V., Javors, M. A., Wood, W. H., Zhang, Y., Becker, K. G., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0083988 · Cited by 145 · see citing works
Molecular Basis of the Rapamycin Insensitivity of Target Of Rapamycin Complex 2
Gaubitz, C., de Oliveira, T. M., Prouteau, M., Leitner, A., Karuppasamy, M., Konstantinidou, G., Rispal, D., Eltschinger, S., Robinson, G., Thore, S., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.04.031 · Cited by 144 · see citing works
Sharp, Z. D., & Bartke, A. (2005) · The Journals of Gerontology Series A · doi:10.1093/gerona/60.3.293 · Cited by 140 · see citing works
Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice
Apelo, S. I. A., Pumper, C. P., Baar, E. L., Richardson, N. E., & Lamming, D. W. (2016) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw064 · Cited by 134 · see citing works
Self-citationZhang, L., Tschumi, B., López‐Mejía, I. C., Oberle, S. G., Meyer, M., Samson, G. P. B., Rüegg, M. A., Hall, M. N., Lluis Fajas, A., Zehn, D., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.095 · Cited by 132 · see citing works
Condon, K. J., Orozco, J. M., Adelmann, C. H., Spinelli, J. B., van der Helm, P. W., Roberts, J. M., Kunchok, T., & Sabatini, D. M. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2022120118 · Cited by 132 · see citing works
Muscle-specific 4E-BP1 signaling activation improves metabolic parameters during aging and obesity
Tsai, S., Sitzmann, J. M., Dastidar, S. G., Rodriguez, A. A., Vu, S. L., McDonald, C. E., Academia, E. C., O’Leary, M. N., Ashe, T. D., Spada, A. R. L., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci77361 · Cited by 130 · see citing works
EPRS is a critical mTORC1–S6K1 effector that influences adiposity in mice
Arif, A., Terenzi, F., Potdar, A. A., Jia, J., Sacks, J., China, A., Halawani, D., Vasu, K. I., Li, X., Brown, J. M., et al. (2017) · Nature · doi:10.1038/nature21380 · Cited by 129 · see citing works
Hurez, V. J., Dao, V. A., Liu, A., Pandeswara, S., Gelfond, J., Sun, L., Bergman, M. A., Orihuela, C. J., Galván, V., Padron, A. S., et al. (2015) · Aging Cell · doi:10.1111/acel.12380 · Cited by 127 · see citing works
Targeting mTOR dependency in pancreatic cancer
Morran, D. C., Wu, J., Jamieson, N. B., Mrowinska, A., Kalna, G., Karim, S. A., Au, A. Y. M., Scarlett, C. J., Chang, D. K.-F., Pajak, M. Z., et al. (2014) · Gut · doi:10.1136/gutjnl-2013-306202 · Cited by 127 · see citing works
Hallowell, R. W., Collins, S. L., Craig, J. M., Zhang, Y., Oh, M. H., Illei, P. B., Chan-Li, Y., Vigeland, C. L., Mitzner, W., Scott, A. L., et al. (2017) · Nature Communications · doi:10.1038/ncomms14208 · Cited by 126 · see citing works
Epilepsy in the mTORopathies: opportunities for precision medicine
Moloney, P. B., Cavalleri, G. L., & Delanty, N. (2021) · Brain Communications · doi:10.1093/braincomms/fcab222 · Cited by 126 · see citing works
Festuccia, W. T., Pouliot, P., Bakan, I., Sabatini, D. M., & Laplante, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0095432 · Cited by 125 · see citing works
Lysosomal GPCR-like Protein LYCHOS Signals Cholesterol Sufficiency to mTORC1
Shin, H. R., Citron, Y. R., Wang, L., Tribouillard, L., Goul, C. S., Stipp, R., Sugasawa, Y., Jain, A., Samson, N., Lim, C.-Y., et al. (2022) · Science · doi:10.1126/science.abg6621 · Cited by 125 · see citing works
Arif, A., Jia, J., Mukhopadhyay, R., Willard, B. B., Kinter, M. T., & Fox, P. L. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.05.028 · Cited by 124 · see citing works
Architecture of human Rag GTPase heterodimers and their complex with mTORC1
Anandapadamanaban, M., Masson, G., Perisic, O., Berndt, A., Kaufman, J., Johnson, C. M., Santhanam, B., Rogala, K. B., Sabatini, D., & Williams, R. L. (2019) · Science · doi:10.1126/science.aax3939 · Cited by 124 · see citing works
Green, C. L., Trautman, M. E., Chaiyakul, K., Jain, R., Alam, Y. H., Babygirija, R., Pak, H. H., Sonsalla, M. M., Calubag, M. F., Yeh, C., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.10.005 · Cited by 124 · see citing works
Self-citationA nutritional memory effect counteracts the benefits of dietary restriction in old mice
Hahn, O., Drews, L. F., Nguyen, A., Tatsuta, T., Gkioni, L., Hendrich, O., Zhang, Q., Langer, T., Pletcher, S. D., Wakelam, M. J. O., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0121-0 · Cited by 122 · see citing works
Mannick, J. B., Teo, G. S. L., Bernardo, P., Quinn, D., Russell, K. S., Klickstein, L. B., Marshall, W., & Shergill, S. (2021) · The Lancet Healthy Longevity · doi:10.1016/s2666-7568(21)00062-3 · Cited by 121 · see citing works
Self-citationDepletion of Rictor, an essential protein component of m TORC 2, decreases male lifespan
Lamming, D. W., Mihaylova, M. M., Katajisto, P., Baar, E. L., Yilmaz, Ö. H., Hutchins, A., Gültekin, Y., Gaither, R., & Sabatini, D. M. (2014) · Aging Cell · doi:10.1111/acel.12256 · Cited by 120 · see citing works
Self-citationComas, M., Toshkov, I. A., Kuropatwinski, K. K., Chernova, O. B., Polinsky, A., Blagosklonny, M. V., Gudkov, A. V., & Antoch, M. P. (2012) · Aging · doi:10.18632/aging.100496 · Cited by 115 · see citing works
Reversal of phenotypes of cellular senescence by pan-mTOR inhibition
Walters, H. E., Deneka-Hannemann, S., & Cox, L. S. (2016) · Aging · doi:10.18632/aging.100872 · Cited by 113 · see citing works
Condon, K. J., Orozco, J. M., Adelmann, C. H., Spinelli, J., van der Helm, P. W., Roberts, J. M., Kunchok, T., & Sabatini, D. (2020) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1101/2020.10.22.351361 · Cited by 112 · see citing works
Greenberger, S., Yuan, S., Walsh, L. A., Boscolo, E., Kang, K.-T., Matthews, B. J., Mulliken, J. B., & Bischoff, J. E. (2011) · Journal of Investigative Dermatology · doi:10.1038/jid.2011.300 · Cited by 111 · see citing works
Cortés, C. J., Qin, K., Cook, J., Solanki, A., & Mastrianni, J. A. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.6189-11.2012 · Cited by 107 · see citing works
The 3.2-Å resolution structure of human mTORC2
Scaiola, A., Mangia, F., Imseng, S., Boehringer, D., Berneiser, K., Shimobayashi, M., Stuttfeld, E., Hall, M. N., Ban, N., & Maier, T. (2020) · Science Advances · doi:10.1126/sciadv.abc1251 · Cited by 104 · see citing works
Chemoprevention and Treatment of Experimental Cowden's Disease by mTOR Inhibition with Rapamycin
SQUARIZE, C. H., CASTILHO, R. M., & Gutkind, J. S. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0922 · Cited by 102 · see citing works
Mieulet, V., Roceri, M., Espeillac, C., Sotiropoulos, A., Ohanna, M., Oorschot, V., Klumperman, J., Sandri, M., & Pende, M. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00499.2006 · Cited by 99 · see citing works
Rapamycin‐mediated mouse lifespan extension: Late‐life dosage regimes with sex‐specific effects
Strong, R., Miller, R. A., Bogue, M. A., Fernández, E., Javors, M. A., Libert, S., Martinez, P. A., Murphy, M. P., Musi, N., Nelson, J. F., et al. (2020) · Aging Cell · doi:10.1111/acel.13269 · Cited by 99 · see citing works
Life Extension by Diet Restriction and N-Acetyl-L-Cysteine in Genetically Heterogeneous Mice
Flurkey, K., Astle, C. M., & Harrison, D. E. (2010) · The Journals of Gerontology Series A · doi:10.1093/gerona/glq155 · Cited by 97 · see citing works
4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1
Yang, H., Wang, J., Liu, M., Chen, X., Huang, M., Tan, D., Wong, C. C. L., Wang, J., Wang, J., Xu, Y., et al. (2016) · Protein & Cell · doi:10.1007/s13238-016-0346-6 · Cited by 96 · see citing works
A small molecule inhibitor of Rheb selectively targets mTORC1 signaling
Mahoney, S. J., Narayan, S., Molz, L., Berstler, L. A., Kang, S. A. W., Vlasuk, G. P., & Saiah, E. (2018) · Nature Communications · doi:10.1038/s41467-018-03035-z · Cited by 95 · see citing works
Yu, D., Tomasiewicz, J. L., Yang, S. E., Miller, B. R., Wakai, M. H., Sherman, D. S., Cummings, N. E., Baar, E. L., Brinkman, J. A., Syed, F. A., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.084 · Cited by 94 · see citing works
Self-citationm TORC 2‐ SGK ‐1 acts in two environmentally responsive pathways with opposing effects on longevity
Mizunuma, M., Neumann‐Haefelin, E., Moroz, N., Li, Y., & Blackwell, T. K. (2014) · Aging Cell · doi:10.1111/acel.12248 · Cited by 93 · see citing works
Senescent Cells Contribute to the Physiological Remodeling of Aged Lungs
Calhoun, C., Shivshankar, P., Saker, M., Sloane, L. B., Livi, C. B., Sharp, Z. D., Orihuela, C. J., Adnot, S., White, E. S., Richardson, A., et al. (2016) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu241 · Cited by 92 · see citing works
Low-dose rapamycin extends lifespan in a mouse model of mtDNA depletion syndrome
Siegmund, S. E., Yang, H., Sharma, R., Javors, M., Skinner, O., Mootha, V., Hirano, M., & Schon, E. A. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx341 · Cited by 92 · see citing works
Dose-dependent effects of mTOR inhibition on weight and mitochondrial disease in mice
Johnson, S. C., Yanos, M. E., Bitto, A., Castanza, A. S., Gagnidze, A., González, B., Gupta, K., Hui, J., Jarvie, C., Johnson, B. M., et al. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00247 · Cited by 91 · see citing works
Haws, S. A., Yu, D., Ye, C., Wille, C. K., Nguyen, L. C., Krautkramer, K. A., Tomasiewicz, J. L., Yang, S. E., Miller, B. R., Liu, W. H., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.03.004 · Cited by 90 · see citing works
Self-citationRegulation of mTOR Activity in Snell Dwarf and GH Receptor Gene-Disrupted Mice
Dominick, G., Berryman, D. E., List, E. O., Kopchick, J. J., Li, X., Miller, R. A., & Garcia, G. G. (2014) · Endocrinology · doi:10.1210/en.2014-1690 · Cited by 89 · see citing works
Rapamycin extends life span of Rb1+/− mice by inhibiting neuroendocrine tumors
Livi, C. B., Hardman, R. L., Christy, B. A., Dodds, S. G., Jones, D., Williams, C. E., Strong, R., Bokov, A. F., Javors, M. A., Ikeno, Y., et al. (2013) · Aging · doi:10.18632/aging.100533 · Cited by 86 · see citing works
Bar‐Peled, L., Chantranupong, L., Cherniack, A. D., Chen, W. W., Ottina, K. A., Grabiner, B. C., Spear, E. D., Carter, S. L., Meyerson, M. M., & Sabatini, D. M. (2013) · The FASEB Journal · doi:10.1096/fasebj.27.1_supplement.832.1 · Cited by 86 · see citing works
Kim, J. H., Lee, C., Lee, M.-J., Wang, H., Kim, K., Park, S. J., Yoon, I., Jang, J., Zhao, H., Kim, H. K., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00785-0 · Cited by 86 · see citing works
The garlic constituent diallyl trisulfide increases the lifespan of C. elegans via skn-1 activation
Powolny, A. A., Singh, S. V., Melov, S., Hubbard, A., & Fisher, A. L. (2011) · Experimental Gerontology · doi:10.1016/j.exger.2011.01.005 · Cited by 83 · see citing works
Chang, K., Kang, P., Liu, Y., Huang, K., Miao, T., Sagona, A. P., Nezis, I. P., Bodmer, R., Ocorr, K. A., & Bai, H. (2019) · Autophagy · doi:10.1080/15548627.2019.1704117 · Cited by 82 · see citing works
Popovich, I. G., Anisimov, V. N., Zabezhinski, M. A., Semenchenko, A. V., Тындык, М. Л., Yurova, M. N., & Blagosklonny, M. V. (2014) · Cancer Biology & Therapy · doi:10.4161/cbt.28164 · Cited by 79 · see citing works
Wang, Y., Liu, Y., Lü, J., Zhang, P., Wang, Y., Xu, Y., Wang, Z., Mao, J., & Wei, G. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.03.077 · Cited by 79 · see citing works
mTOR drives cerebrovascular, synaptic, and cognitive dysfunction in normative aging
Skike, C. E. V., Lin, A., Burbank, R. R., Halloran, J. J., Hernandez, S. F., Cuvillier, J., Soto, V. Y., Hussong, S. A., Jahrling, J. B., Javors, M. A., et al. (2019) · Aging Cell · doi:10.1111/acel.13057 · Cited by 79 · see citing works
Shindyapina, A. V., Cho, Y., Kaya, A., Tyshkovskiy, A., Castro, J. P., Deik, A., Gordevičius, J., Poganik, J. R., Clish, C. B., Horvath, S., et al. (2022) · Science Advances · doi:10.1126/sciadv.abo5482 · Cited by 79 · see citing works
Leontieva, O. V., Paszkiewicz, G., & Blagosklonny, M. V. (2014) · Aging Cell · doi:10.1111/acel.12211 · Cited by 78 · see citing works
Rapamycin improves healthspan but not inflammaging in <i>nfκb1</i><sup>−/−</sup> mice
Correia‐Melo, C., Birch, J., Fielder, E., Rahmatika, D., Taylor, J., Chapman, J., Lagnado, A., Carroll, B. M., Miwa, S., Richardson, G., et al. (2019) · Aging Cell · doi:10.1111/acel.12882 · Cited by 77 · see citing works
Translation fidelity coevolves with longevity
Ke, Z., Mallik, P., Johnson, A. B., Luna, F., Nevo, E., Zhang, Z. D., Gladyshev, V. N., Seluanov, A., & Gorbunova, V. A. (2017) · Aging Cell · doi:10.1111/acel.12628 · Cited by 76 · see citing works
Diminished mTOR signaling: a common mode of action for endocrine longevity factors
Lamming, D. W. (2014) · SpringerPlus · doi:10.1186/2193-1801-3-735 · Cited by 74 · see citing works
Self-citationmTORC1 and mTORC2 differentially promote natural killer cell development
Yang, C., Tsaih, S., Lemke, A., Flister, M. J., Thakar, M. S., & Malarkannan, S. (2018) · eLife · doi:10.7554/elife.35619 · Cited by 73 · see citing works
The mTOR pathway is necessary for survival of mice with short telomeres
Ferrara‐Romeo, I., Martínez, P., Saraswati, S., Whittemore, K., Graña‐Castro, O., Poluha, L. T., Serrano, R., Hernández-Encinas, E., Blanco‐Aparicio, C., Flores, J. M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14962-1 · Cited by 73 · see citing works
Lee, N. Y., Woodrum, C., Nobil, A. M., Rauktys, A., Messina, M. P., & Dabora, S. L. (2009) · BMC Pharmacology · doi:10.1186/1471-2210-9-8 · Cited by 72 · see citing works
Meng, J.-G., & Ferguson, S. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201712177 · Cited by 70 · see citing works
Autophagy and ageing: Insights from invertebrate model organisms
Lionaki, E., Markaki, M., & Tavernarakis, N. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2012.05.001 · Cited by 69 · see citing works
eRapa Restores a Normal Life Span in a FAP Mouse Model
Hasty, P., Livi, C. B., Dodds, S. G., Jones, D., Strong, R., Javors, M. A., Fischer, K. E., Sloane, L. B., Murthy, K., Hubbard, G. B., et al. (2013) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-13-0299 · Cited by 68 · see citing works
Trelińska, J., Dachowska, I., Kotulska, K., Fendler, W. M., Jóźwiak, S., & Mlynarski, W. M. (2015) · Anti-Cancer Drugs · doi:10.1097/cad.0000000000000207 · Cited by 67 · see citing works
Strong, R., Miller, R. A., Cheng, C. J. A., Nelson, J. F., Gelfond, J., Allani, S. K., Diaz, V., Dorigatti, A. O., Dorigatti, J. D., Fernández, E., et al. (2022) · Aging Cell · doi:10.1111/acel.13724 · Cited by 67 · see citing works
Tsai, S., Rodriguez, A. A., Dastidar, S. G., Greco, E. D., Carr, K. L., Sitzmann, J. M., Academia, E. C., Viray, C. M., Martinez, L. L., Kaplowitz, B., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.07.029 · Cited by 66 · see citing works
Rapamycin Increases Mortality in<i>db/db</i>Mice, a Mouse Model of Type 2 Diabetes
Sataranatarajan, K., Ikeno, Y., Bokov, A., Feliers, D., Yalamanchili, H., Lee, H. J., Mariappan, M. M., Tabatabai-Mir, H., Diaz, V., Prasad, S., et al. (2016) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glv170 · Cited by 65 · see citing works
Hypothalamic mTORC2 is essential for metabolic health and longevity
Chellappa, K., Brinkman, J. A., Mukherjee, S., Morrison, M., Alotaibi, M., Carbajal, K. A., Alhadeff, A. L., Perron, I. J., Yao, R., Purdy, C. S., et al. (2019) · Aging Cell · doi:10.1111/acel.13014 · Cited by 65 · see citing works
Self-citationHan, X., Turdi, S., Hu, N., Guo, R., Zhang, Y., & Ren, J. T. (2012) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2011.11.002 · Cited by 64 · see citing works
Rapamycin Reverses Metabolic Deficits in Lamin A/C-Deficient Mice
Liao, C.-Y., Anderson, S. S., Chicoine, N. H., Mayfield, J., Academia, E. C., Wilson, J. A., Pongkietisak, C., Thompson, M. A., Lagmay, E. P., Miller, D. M., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.10.040 · Cited by 61 · see citing works
mTOR inhibition acts as an unexpected checkpoint in p53-mediated tumor suppressionPreprint
Kon, N., Ou, Y., Wang, S.-J., Li, H., Rustgi, A. K., & Gu, W. J. (2020) · Genes & Development · doi:10.1101/gad.340919.120 · Cited by 61 · see citing works
Garratt, M., Lagerborg, K. A., Tsai, Y., Gałecki, A. T., Jain, M., & Miller, R. A. (2018) · Aging Cell · doi:10.1111/acel.12786 · Cited by 60 · see citing works
Rapamycin inhibits oncogenic intestinal ion channels and neoplasia in APCMin/+ mice
Koehl, G. E., Spitzner, M., Ousingsawat, J., Schreiber, R., Geissler, E. K., & Kunzelmann, K. (2009) · Oncogene · doi:10.1038/onc.2009.435 · Cited by 59 · see citing works
White, Z. R., White, R. B., McMahon, C., Grounds, M. D., & Shavlakadze, T. (2016) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2016.06.012 · Cited by 59 · see citing works
Mitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation.
Kim, S.-H., Choi, J.-H., Wang, P., Go, C. D., Hesketh, G., Gingras, A., Jafarnejad, S. M., & Sonenberg, N. (2020) · Molecules and Cells · doi:10.1016/j.molcel.2020.11.036 · Cited by 56 · see citing works
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Mechanisms of long COVID and the path toward therapeutics
Peluso, M. J., & Deeks, S. G. (2024) · Cell · doi:10.1016/j.cell.2024.07.054 · Cited by 356 · see citing works
Molecular mechanisms of aging and anti-aging strategies
Li, Y., Tian, X., Luo, J., Bao, T., Wang, S., & Wu, X. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01663-1 · Cited by 333 · see citing works
Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology
Settembre, C., & Perera, R. M. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00676-x · Cited by 296 · see citing works
Autophagy, aging, and age-related neurodegeneration
Palmer, J. E., Wilson, N., Son, S. M., Obrocki, P., Wróbel, L., Rob, M., Takla, M., Korolchuk, V. I., & Rubinsztein, D. C. (2024) · Neuron · doi:10.1016/j.neuron.2024.09.015 · Cited by 255 · see citing works
The Nrf2-HO-1 system and inflammaging
O’Rourke, S. A., Shanley, L. C., & Dunne, A. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1457010 · Cited by 167 · see citing works
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165 · see citing works
Kuzu, O., Granerud, L. J. T., & Saatcioglu, F. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02439-w · Cited by 107 · see citing works
The 3 I’s of immunity and aging: immunosenescence, inflammaging, and immune resilience
Wrona, M. V., Ghosh, R. B., Coll, K., Chun, C., & Yousefzadeh, M. J. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1490302 · Cited by 102 · see citing works
Mihaylova, M. M., Chaix, A., Delibegović, M., Ramsey, J. J., Bass, J. T., Melkani, G. C., Singh, R., Chen, Z., Ja, W. W., Shirasu-Hiza, M., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.06.008 · Cited by 91 · see citing works
Self-citationp53/MDM2 signaling pathway in aging, senescence and tumorigenesis
Huang, Y., Che, X., Wang, P., & Qu, X. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.05.001 · Cited by 92 · see citing works
Pathological mechanisms and treatment progression of Alzheimer’s disease
Zhang, J., Kong, G., Yang, J., Pang, L., & Li, X. (2025) · European journal of medical research · doi:10.1186/s40001-025-02886-9 · Cited by 94 · see citing works
mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics
Zhang, H., Xiao, X., Pan, Z., & Dokudovskaya, S. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02493-4 · Cited by 91 · see citing works
Tassone, F., Protic, D. D., Allen, E. G., Archibald, A. D., Baud, A., Brown, T. W., Budimirovic, D. B., Cohen, J., Dufour, B. D., Eiges, R., et al. (2023) · Cells · doi:10.3390/cells12182330 · Cited by 76 · see citing works
Emerging epigenetic insights into aging mechanisms and interventions
Wu, Z., Zhang, W., Qu, J. T., & Liu, G. (2024) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2023.12.002 · Cited by 74 · see citing works
Oxidative Stress-Driven Cellular Senescence: Mechanistic Crosstalk and Therapeutic Horizons
Stojanović, B., Jovanovic, I., Stojanovic, M. D., Stojanović, B., Kovačević, V., Radosavljević, I., Jovanović, D., Kovačević, M. M., Zornić, N., Arsić, A. A., et al. (2025) · Antioxidants · doi:10.3390/antiox14080987 · Cited by 83 · see citing works
Skin health and biological aging
Furman, D., Auwerx, J. H., Bulteau, A., Church, G. M., Couturaud, V., Crabbé, L., Davies, K. J. A., Decottignies, A., Gladyshev, V. N., Kennedy, B. K., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00901-6 · Cited by 72 · see citing works
Li, Y., Berliocchi, L., Li, Z., & Rasmussen, L. J. (2023) · Aging Cell · doi:10.1111/acel.13942 · Cited by 65 · see citing works
Targeting organ-specific mitochondrial dysfunction to improve biological aging
Madreiter‐Sokolowski, C. T., Hiden, U., Krstić, J., Panzitt, K., Wagner, M., Enzinger, C., Khalil, M., Abdellatif, M., Malle, E., Madl, T., et al. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108710 · Cited by 54 · see citing works
Liang, L., Yue, Y., Zhong, L., Liang, Y., Ruixiang, S. H. I., Luo, R., Zhao, M., Cao, X., Yang, M., Du, J., et al. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.127647 · Cited by 49 · see citing works
Immune Alterations with Aging: Mechanisms and Intervention Strategies
Yu, W., Yu, Y., Sun, S., Lu, C., Zhai, J., Lei, Y., Bai, F., Wang, R., & Chen, J. (2024) · Nutrients · doi:10.3390/nu16223830 · Cited by 52 · see citing works
Blazing a trail for the clinical use of rapamycin as a geroprotecTOR
Konopka, A., Lamming, D., Grasso, B. A., Marrah, R. C., Decker, S. A., Garg, N., Park, Y., Lim, S.-Y., Simcox, J. A., Green, C. L., et al. (2023) · GeroScience · doi:10.1007/s11357-023-00935-x · Cited by 44 · see citing works
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Fu, Y., Jiang, F., Zhang, X., Pan, Y., Xu, R., Liang, X. H., Wu, X., Li, X., Lin, K., Shi, R., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49796-8 · Cited by 45 · see citing works
Lyu, Y.-X., Fu, Q., Wilczok, D., Ying, K., King, A., Antebi, A., Vojta, A., Stolzing, A., Moskalev, A., Georgievskaya, A., et al. (2024) · Aging · doi:10.18632/aging.206135 · Cited by 46 · see citing works
Self-citationSvensson, J. E., Bolin, M., Thor, D., Williams, P. A., Brautaset, R., Carlsson, M., Sörensson, P., Marlevi, D., Spin‐Neto, R., Probst, M., et al. (2024) · BMC Neurology · doi:10.1186/s12883-024-03596-1 · Cited by 44 · see citing works
Teng, H., Xiao, H., Li, X., Huang, J., Zhang, B., & Zeng, M. (2025) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2025.105000 · Cited by 46 · see citing works
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Patel, C. H., & Powell, J. D. (2025) · Immunity · doi:10.1016/j.immuni.2025.06.010 · Cited by 43 · see citing works
Cellular Senescence in Health, Disease, and Lens Aging
Qin, Y., Liu, H., & Wu, H. (2025) · Pharmaceuticals · doi:10.3390/ph18020244 · Cited by 43 · see citing works
Gkioni, L., Nespital, T., Baghdadi, M., Monzó, C., Bali, J., Nassr, T., Cremer, A. L., Beyer, A., Deelen, J., Backes, H., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00876-4 · Cited by 41 · see citing works
Senescence, NK cells, and cancer: navigating the crossroads of aging and disease
Gergues, M., Bari, R., Koppisetti, S., Gosiewska, A., Kang, L., & HARIRI, R. J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1565278 · Cited by 42 · see citing works
Epigenetic Regulation of Aging and its Rejuvenation
An, Y., Wang, Q., Gao, K., Zhang, C., Ouyang, Y., Li, R., Zhou, M., Wu, T., Zhou, L., Xie, Z., et al. (2025) · MedComm · doi:10.1002/mco2.70369 · Cited by 44 · see citing works
Anti-ageing interventions for the treatment of cardiovascular disease
Abdellatif, M., Schmid, S., Fuerlinger, A., & Kroemer, G. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae177 · Cited by 37 · see citing works
Sun, B., Li, L., Harris, O. A., & Luo, J. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00478-5 · Cited by 43 · see citing works
Age-associated changes in innate and adaptive immunity: role of the gut microbiota
Gao, H., Nepovimová, E., Adam, V., Heger, Z., Valko, M., Wu, Q., & Kuča, K. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1421062 · Cited by 37 · see citing works
Kritchevsky, S. B., & Cummings, S. R. (2025) · JAMA · doi:10.1001/jama.2025.11289 · Cited by 38 · see citing works
Luo, Z., Wei, W., Qiu, D., Su, Z., Liu, L., Zhou, H., Cui, H., & Yang, L. (2024) · Bone Research · doi:10.1038/s41413-024-00351-7 · Cited by 35 · see citing works
Rapamycin for longevity: the pros, the cons, and future perspectives
Roark, K. M., & Iffland, P. H. (2025) · Frontiers in Aging · doi:10.3389/fragi.2025.1628187 · Cited by 37 · see citing works
mTORC1 in energy expenditure: consequences for obesity
Allard, C., Miralpeix, C., López-Gambero, A. J., & Cota, D. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00934-0 · Cited by 29 · see citing works
Molecular hallmarks of ageing in amyotrophic lateral sclerosis
Jagaraj, C. J., Shadfar, S., Kashani, S. A., Saravanabavan, S., Farzana, F., & Atkin, J. D. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05164-9 · Cited by 33 · see citing works
Late-life protein or isoleucine restriction impacts physiological and molecular signatures of aging
Yeh, C., Chini, L., Davidson, J. W., Garcia, G. G., Gallagher, M. S., Freichels, I. T., Calubag, M. F., Rodgers, A. C., Green, C. L., Babygirija, R., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00744-7 · Cited by 32 · see citing works
Self-citationA nutrigeroscience approach: Dietary macronutrients and cellular senescence
Calubag, M. F., Robbins, P. D., & Lamming, D. W. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.07.025 · Cited by 32 · see citing works
Self-citationYao, W., Zhang, Y., & Zhang, G. (2024) · Food Chemistry · doi:10.1016/j.foodchem.2024.140413 · Cited by 31 · see citing works
Fan, Y., Yuan, J., Somekh, J., Mor Peleg, B., Zhu, Y., Jia, Z., Wu, F. L., & Huang, Z. (2025) · Science Advances · doi:10.1126/sciadv.adr3757 · Cited by 28 · see citing works
Popescu, I. R., Deelen, J., Illario, M., & Adams, J. (2023) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17912 · Cited by 28 · see citing works
Current and Future Treatments of Vascular Cognitive Impairment
Ip, B. Y. M., Ko, H., Lam, B. Y. K., Au, L. W. C., Lau, A. Y. L., Huang, J., Kwok, A. J., Leng, X., Cai, Y., Leung, T. W. H., et al. (2024) · Stroke · doi:10.1161/strokeaha.123.044174 · Cited by 26 · see citing works
Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results
Harinath, G., Lee, V., Nyquist, A., Moel, M., Morgan, S. L., Isman, A., & Zalzala, S. (2025) · Aging · doi:10.18632/aging.206235 · Cited by 37 · see citing works
Aging reshapes the adaptive immune system from healer to saboteur
Delgado-Pulido, S., Yousefzadeh, M. J., & Mittelbrunn, M. (2025) · Nature Aging · doi:10.1038/s43587-025-00906-1 · Cited by 29 · see citing works
GCN1 couples GCN2 to ribosomal state to initiate amino acid response pathway signaling
Zhou, C., Zhang, M., Murray, J., Paulo, J. A., Gygi, S. P., Shao, S., Whitman, M., & Keller, T. L. (2025) · Science · doi:10.1126/science.ads8728 · Cited by 30 · see citing works
Roles of Stress Response in Autophagy Processes and Aging-Related Diseases
Watanabe, Y., Taguchi, K., & Tanaka, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813804 · Cited by 26 · see citing works
Baghdadi, M., Nespital, T., Monzó, C., Deelen, J., Grönke, S., & Partridge, L. (2024) · Molecular Metabolism · doi:10.1016/j.molmet.2024.101902 · Cited by 27 · see citing works
Effects of Ginger (Zingiber officinale) on the Hallmarks of Aging
Matin, M., Joshi, T., Wang, D., Tzvetkov, N. T., Matin, F. B., Wierzbicka, A., Jóźwik, A., Horbańczuk, J. O., & Atanasov, A. G. (2024) · Biomolecules · doi:10.3390/biom14080940 · Cited by 25 · see citing works
Single-cell and spatial transcriptomics analysis of human adrenal aging
Iwahashi, N., Umakoshi, H., Fujita, M., Fukumoto, T., Ogasawara, T., Yokomoto‐Umakoshi, M., Kaneko, H., Nakao, H., Kawamura, N., Uchida, N., et al. (2024) · Molecular Metabolism · doi:10.1016/j.molmet.2024.101954 · Cited by 24 · see citing works
Mandelblatt, J. S., Antoni, M. H., Bethea, T. N., Cole, S. W., Hudson, B. I., Penedo, F. J., Ramírez, A. G., Rebeck, G. W., Sarkar, S., Schwartz, A. G., et al. (2024) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djae211 · Cited by 24 · see citing works
Ginkgolide B increases healthspan and lifespan of female mice
Lee, C., Wang, B. Y., Wong, S. H., Chen, Y., Cao, Q., Hsiao, A. W., Fung, S.-H., Chen, Y.-F., Wu, H.-H., Cheng, P.-Y., et al. (2025) · Nature Aging · doi:10.1038/s43587-024-00802-0 · Cited by 24 · see citing works
Body-wide multi-omic counteraction of aging with GLP-1R agonism
Huang, J., Kwok, A. J., Li, J. C. Y., Chiu, C. L. H., Ip, B. Y. M., Tung, L. Y., Chan, R. C. H., Chan, D. T.-M., Wang, Z., Zheng, X., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.10.014 · Cited by 31 · see citing works
Geroprotector drugs and exercise: friends or foes on healthy longevity?
Elliehausen, C. J., Anderson, R. M., Diffee, G. M., Rhoads, T. W., Lamming, D. W., Hornberger, T. A., & Konopka, A. R. (2023) · BMC Biology · doi:10.1186/s12915-023-01779-9 · Cited by 24 · see citing works
Self-citationMechanisms of Senescence and Anti-Senescence Strategies in the Skin
Konstantinou, E. K., Longange, E., & Kaya, G. (2024) · Biology · doi:10.3390/biology13090647 · Cited by 26 · see citing works
Wellens, J., Vissers, E., Dumoulin, A., Hoekx, S., Vanderstappen, J., Verbeke, J., Vangoitsenhoven, R., Derrien, M., Verstockt, B., Ferrante, M., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102091 · Cited by 23 · see citing works
Research progress on interferon and cellular senescence
Wang, D., Chen, K., Wang, Z., Wu, H., & Li, Y. (2024) · The FASEB Journal · doi:10.1096/fj.202400808rr · Cited by 23 · see citing works
Pietrogrande, G., Shaker, M. R., Stednitz, S. J., Soheilmoghaddam, M., Aguado, J., Morrison, S. D., Zambrano, S., Tabassum, T., Javed, I., Cooper-White, J. J., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02732-0 · Cited by 22 · see citing works
Aging Lung: Molecular Drivers and Impact on Respiratory Diseases—A Narrative Clinical Review
Górski, P., Białas, A. J., & Piotrowski, W. J. (2024) · Antioxidants · doi:10.3390/antiox13121480 · Cited by 23 · see citing works
Cardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets
Zheng, P., Yan, W., Ding, Y.-N., Zhang, Y., Chen, Z., Qian, J., & Ge, J. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02630-7 · Cited by 26 · see citing works
Siwach, A., Patel, H., Khairnar, A., & Parekh, P. (2025) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70192 · Cited by 21 · see citing works
Dietary methionine restriction started late in life promotes healthy aging in a sex-specific manner
Hernández-Arciga, U., Stamenkovic, C., Yadav, S., Nicoletti, C., Albalawy, W. N., hammood, F. A., Gonzalez, T. F., Naikwadi, M. U., Graham, A., Smarz, C., et al. (2025) · Science Advances · doi:10.1126/sciadv.ads1532 · Cited by 24 · see citing works
Translatability of life‐extending pharmacological treatments between different species
Burdusel, D., Coman, C., Ancuța, D.-L., Hermann, D. M., Doeppner, T. R., Greșiță, A., & Popa‐Wagner, A. (2024) · Aging Cell · doi:10.1111/acel.14208 · Cited by 20 · see citing works
Cormerais, Y., Lapp, S. C., Kalafut, K. C., Cissé, M. Y., Shin, J., Stefadu, B., Personnaz, J., Schrotter, S., Freed, J., D’Amore, A., et al. (2025) · Developmental Cell · doi:10.1016/j.devcel.2025.05.008 · Cited by 15 · see citing works
Cui, Z., Li, J., Li, C., Deng, S., Liu, W., Lei, T., Cao, J., Wang, Z., Wang, X., Ma, S., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115917 · Cited by 21 · see citing works
Baseline immune states (BIS) associated with vaccine responsiveness and factors that shape the BIS
Nehar-Belaid, D., Sokolowski, M. J., Ravichandran, S., Banchereau, J., Chaussabel, D., & Ucar, D. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101842 · Cited by 19 · see citing works
Autophagy-targeting modulation to promote peripheral nerve regeneration
Chen, Y., Deng, H., & Zhang, N. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01948 · Cited by 19 · see citing works
Rapamycin enhances CAR-T control of HIV replication and reservoir elimination in vivo
Mu, W., Tomer, S., Harding, J. S., Kedia, N., Rezek, V. K., Cook, E., Patankar, V., Carrillo, M. A., Martin, H. A., Ng, H. L., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci185489 · Cited by 19 · see citing works
Sheppard, A. J., Delgado, K., Barfield, A. M., Xu, Q., Massey, P. A., Dong, Y., & Barton, R. S. (2024) · Stem Cell Reviews and Reports · doi:10.1007/s12015-024-10682-x · Cited by 18 · see citing works
Kosakamoto, H., Sakuma, C., Okada, R., Miura, M., & Obata, F. (2024) · Science Advances · doi:10.1126/sciadv.adn7167 · Cited by 18 · see citing works
Ma, X., Mao, M., Liu, Z., Liang, C. L., He, J., Qu, Y., Xu, L., Cheng, R., Zhuang, W., Lei, Y., et al. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.4c11072 · Cited by 18 · see citing works
TRIM-endous functional network of tripartite motif 29 (TRIM29) in cancer progression and beyond
Wu, Q., Nandi, D., & Sharma, D. (2024) · Cancer and Metastasis Reviews · doi:10.1007/s10555-024-10226-2 · Cited by 20 · see citing works
Kelu, J. J., & Hughes, S. M. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2422446122 · Cited by 19 · see citing works
The Immune System and Cellular Senescence: A Complex Interplay in Aging and Disease
Ayoub, M., Jaoude, C. A., Ayoub, M., Hamadé, A., & Rima, M. (2025) · Immunology · doi:10.1111/imm.70036 · Cited by 22 · see citing works
Compression of morbidity by interventions that steepen the survival curve
Yang, Y., Mayo, A., Levy, T., Raz, N., Shenhar, B., Jarosz, D. F., & Alon, U. (2025) · Nature Communications · doi:10.1038/s41467-025-57807-5 · Cited by 16 · see citing works
Nanomedicines Against Mitochondrial Dysfunction‐Induced Metabolic Diseases
Xu, K., Wang, L., Lv, T., Jin, C., Wu, Q., Zhou, Y., Xu, G., Duan, Z., Luo, K., & Yang, J. (2025) · Advanced Science · doi:10.1002/advs.202514522 · Cited by 18 · see citing works
Immune Diseases Associated with Aging: Molecular Mechanisms and Treatment Strategies
Kim, M. E., & Lee, J. S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242115584 · Cited by 17 · see citing works
Nurturing longevity through natural compounds: Where do we stand, and where do we go?
Todorova, M. N., Savova, M. S., Mihaylova, L. V., & Georgiev, M. I. (2024) · Food Frontiers · doi:10.1002/fft2.350 · Cited by 17 · see citing works
Mitochondrial One-Carbon Metabolism and Alzheimer’s Disease
Yu, Y., & Martins, L. M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126302 · Cited by 17 · see citing works
Lost in translation: challenges of current pharmacotherapy for sarcopenia
Tsai, S. (2024) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2024.05.016 · Cited by 18 · see citing works
Microbial natural compounds and secondary metabolites as Immunomodulators: A review
Mahmoudi, F., Jalayeri, M. H. T., Montaseri, A., Khosroshahi, L. M., & Baradaran, B. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.134778 · Cited by 19 · see citing works
Brain Plasticity and Cell Competition: Immediate Early Genes Are the Focus
Tregub, P. P., Komleva, Y. K., Kukla, M. V., Сергеевич, А. А., Vetchinova, A. S., Rozanova, N. A., Illarioshkin, S. N., & Salmina, A. B. (2025) · Cells · doi:10.3390/cells14020143 · Cited by 19 · see citing works
Dong, J., Wang, Q., Gu, T., Liu, G., Petrov, Y. V., Баулин, В. Е., Tsivadze, A. Y., Jia, D., Zhou, Y., Yuan, H., et al. (2024) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2024.01.032 · Cited by 16 · see citing works
Obata, F., & Miura, M. (2024) · Annual Review of Genetics · doi:10.1146/annurev-genet-111523-102042 · Cited by 16 · see citing works
Targeting a mTOR/autophagy axis: a double-edged sword of rapamycin in spontaneous miscarriage
Li, M., Shen, H.-H., Cao, X.-Y., Gao, X.-X., Xu, F.-Y., Ha, S., Sun, J., Liu, S., Xie, F., & Li, M. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116976 · Cited by 18 · see citing works
Duan, H., Yu, Q., Ni, Y., Li, J., Yu, L., Yan, X., & Fan, L. (2024) · Food Bioscience · doi:10.1016/j.fbio.2024.104615 · Cited by 16 · see citing works
Sharma, N., Singh, L., Sharma, A., Kumar, A., & Mahajan, D. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107375 · Cited by 16 · see citing works
Combinatorial interventions in aging
Parkhitko, A. A., Filine, E., & Tatar, M. (2023) · Nature Aging · doi:10.1038/s43587-023-00489-9 · Cited by 16 · see citing works
Shafqat, A., Masters, M. C., Tripathi, U., Tchkonia, T., Kirkland, J. L., & Hashmi, S. K. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102400 · Cited by 15 · see citing works
A high-fiber diet mimics aging-related signatures of caloric restriction in mammals
Hu, F., Yu, L., Tu, X., Huang, R., Yan, X., Wang, L., Wei, X., Wei, X., & Wu, Z. (2025) · Nature Communications · doi:10.1038/s41467-025-61046-z · Cited by 14 · see citing works
mTORC1 senses glutamine and other amino acids through GCN2
Figlia, G., Müller, S., Garcia-Cortizo, F., Neff, M., Klinke, G., Poschet, G., & Teleman, A. A. (2025) · EMBO Journal · doi:10.1038/s44318-025-00505-1 · Cited by 17 · see citing works
Next-generation T cell immunotherapy: overcoming exhaustion, senescence, and suppression
Li, G., Li, D., & Zhu, X. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1662145 · Cited by 15 · see citing works
Common features between aging and cancer: a narrative review
Abubakar, M., Hameed, Y., Kiani, M. N., & Aftab, A. (2024) · Aging advances. · doi:10.4103/agingadv.agingadv-d-24-00023 · Cited by 14 · see citing works
Șerban, M., Toader, C., & Covache-Busuioc, R.-A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26168072 · Cited by 15 · see citing works
The impacts of different dietary restriction regimens on aging and longevity: from yeast to humans
Ching, T., & Hsu, A. (2025) · Journal of Biomedical Science · doi:10.1186/s12929-025-01188-w · Cited by 15 · see citing works
Kell, L., Jones, E. J., Gharahdaghi, N., Wilkinson, D. J., Smith, K., Atherton, P. J., Simon, A. K., Cox, L. S., & Alsaleh, G. (2026) · Aging Cell · doi:10.1111/acel.70364 · Cited by 13 · see citing works
Rivas, V. N., Kaplan, J. L., Kennedy, S. A., Fitzgerald, S., Crofton, A. E., Farrell, A., Grubb, L., Jauregui, C. E., Grigorean, G., Choi, E. A., et al. (2023) · Animals · doi:10.3390/ani13203184 · Cited by 13 · see citing works
Yu, Y., Meng, X., Fu, H., Lu, S., Yang, J., Geng, C., Li, X., Gu, W., Zhou, J., & Meng, Q. (2024) · Aquaculture · doi:10.1016/j.aquaculture.2024.740556 · Cited by 13 · see citing works
The proteomic landscape of microglia in health and disease
Davis, E., & Lloyd, A. F. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1379717 · Cited by 12 · see citing works
- Authors
- Mannick, J. B., & Lamming, D. W.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Lamming, Dudley W.
- Venue
- Nature Aging
- Published
- 2023-05-04
- Volume
- 3
- Issue
- 6
- Pages
- 642-660
- ISSN
- 2662-8465 (ISSN-L)
- PMC
- PMC10330278
- OpenAlex
- W4368374116
- Cited by
- 372
- References
- 256
- Citations by year
- 2026: 103 · 2025: 135 · 2024: 116 · 2023: 18
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Aging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (AG056771, AG062328, AG061635 and AG076941)
- U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (DK125859)
- U.S. Department of Veterans Affairs (BX004031)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mTOR inhibitors, rapamycin, mTORC1, aging, longevity, age-related diseases, clinical trials, mouse model, drug safety
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, MTOR Inhibitors, Aging, Animals, Biology, Humans, United States, Sirolimus, Mice, TOR Serine-Threonine Kinases
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