Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity

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

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

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 2,659 · see citing works

Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys

Colman, R. J., Anderson, R. M., Johnson, S. C., Kastman, E. K., Kosmatka, K. J., Beasley, T. M., Allison, D. B., Cruzen, C., Simmons, H. A., Kemnitz, J. W., et al. (2009) · Science · doi:10.1126/science.1173635 · Cited by 2,277 · see citing works

mTOR controls mitochondrial oxidative function through a YY1–PGC-1α transcriptional complex

Cunningham, J. T., Rodgers, J. T., Arlow, D. H., Vazquez, F., Mootha, V. K., & Puigserver, P. (2007) · Nature · doi:10.1038/nature06322 · Cited by 1,488 · see citing works

Ablation in Mice of the mTORC Components raptor, rictor, or mLST8 Reveals that mTORC2 Is Required for Signaling to Akt-FOXO and PKCα, but Not S6K1

Guertin, D. A., Stevens, D. M., Thoreen, C. C., Burds, A. A., Kalaany, N. Y., Moffat, J., Brown, M., Fitzgerald, K. J., & Sabatini, D. M. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.10.007 · Cited by 1,409 · see citing works

Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue

Blüher, M., Kahn, B. B., & Kahn, C. R. (2003) · Science · doi:10.1126/science.1078223 · Cited by 1,348 · see citing works

Obesity-associated improvements in metabolic profile through expansion of adipose tissue

Kim, J.-Y., van de Wall, E., Laplante, M., Azzara, A., Trujillo, M. E., Hofmann, S. M., Schraw, T., Durand, J. L., Li, H., Li, G., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31021 · Cited by 1,310 · 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

Ribosomal 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

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

Calorie restriction, SIRT1 and metabolism: understanding longevity

Bordone, L., & Guarente, L. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1616 · Cited by 1,021 · see citing works

mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)

García-Martínez, J. M., & Alessi, D. R. (2008) · Biochemical Journal · doi:10.1042/bj20081668 · Cited by 907 · see citing works

Deletion of the Developmentally Essential Gene ATR in Adult Mice Leads to Age-Related Phenotypes and Stem Cell Loss

Ruzankina, Y., Pinzon‐Guzman, C., Asare, A., Ong, T., Pontano, L. L., Cotsarelis, G., Zediak, V. P., Velez, M., Bhandoola, A., & Brown, E. J. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.03.002 · Cited by 780 · see citing works

Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

Anson, R. M., Guo, Z., de Cabo, R., Iyun, T., Rios, M., Hagepanos, A., Ingram, D. K., Lane, M. A., & Mattson, M. P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1035720100 · Cited by 732 · 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

mTORC1 controls fasting-induced ketogenesis and its modulation by ageing

Sengupta, S., Peterson, T. R., Laplante, M., Oh, S., & Sabatini, D. M. (2010) · Nature · doi:10.1038/nature09584 · Cited by 646 · see citing works

Skeletal Muscle-Specific Ablation of raptor, but Not of rictor, Causes Metabolic Changes and Results in Muscle Dystrophy

Bentzinger, C. F., Romanino, K., Cloëtta, D., Lin, S., Mascarenhas, J. B., Oliveri, F., Xia, J., Casanova, E., Costa, C. F., Brink, M., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.10.002 · Cited by 640 · see citing works

Evidence for lifespan extension and delayed age–related biomarkers in insulin receptor substrate 1 null mice

Selman, C., Lingard, S., Choudhury, A. I., Batterham, R. L., Claret, M., Clements, M., Ramadani, F., Okkenhaug, K., Schuster, E., Blanc, E., et al. (2008) · The FASEB Journal · doi:10.1096/fj.07-9261com · Cited by 532 · see citing works

Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis

Taguchi, A., Wartschow, L. M., & White, M. F. (2007) · Science · doi:10.1126/science.1142179 · Cited by 523 · see citing works

Chronic Rapamycin Treatment Causes Glucose Intolerance and Hyperlipidemia by Upregulating Hepatic Gluconeogenesis and Impairing Lipid Deposition in Adipose Tissue

Houde, V. P., Brûlé, S., Festuccia, W. T., Blanchard, P.-G., Bellmann, K., Deshaies, Y., & Marette, A. (2010) · Diabetes · doi:10.2337/db09-1324 · Cited by 456 · 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

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

mTOR Inhibition by Rapamycin Prevents β-Cell Adaptation to Hyperglycemia and Exacerbates the Metabolic State in Type 2 Diabetes

Fraenkel, M., Ketzinel‐Gilad, M., Ariav, Y., Pappo, O., Karaca, M., Castel, J., Berthault, M., Magnan, C., Cerasi, E., Kaiser, N., et al. (2008) · Diabetes · doi:10.2337/db07-0922 · Cited by 380 · see citing works

Targeted expression of catalase to mitochondria prevents age-associated reductions in mitochondrial function and insulin resistance

Lee, H.-Y., Choi, C. S., Birkenfeld, A. L., Alves, T. C., Jornayvaz, F. R., Jurczak, M. J., Zhang, D., Woo, D. K., Shadel, G. S., Ladiges, W., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.11.004 · Cited by 319 · see citing works

MSN2 and MSN4 Link Calorie Restriction and TOR to Sirtuin-Mediated Lifespan Extension in Saccharomyces cerevisiae

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

Fat Cell–Specific Ablation of Rictor in Mice Impairs Insulin-Regulated Fat Cell and Whole-Body Glucose and Lipid Metabolism

Kumar, A. T., Lawrence, J. C., Jung, D. Y., Ko, H. J., Keller, S. R., Kim, J. K., Magnuson, M. A., & Harris, T. E. (2010) · Diabetes · doi:10.2337/db09-1061 · Cited by 250 · see citing works

Glucose Metabolism in Renal Transplant Recipients

Teutonico, A., Schena, P. F., & Paolo, S. D. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2005050487 · Cited by 238 · see citing works

Increased insulin sensitivity and upregulation of insulin receptor, insulin receptor substrate (IRS)-1 and IRS-2 in liver of Ames dwarf mice

Dominici, F. P., Hauck, S., Argentino, D., Bartke, A., & Turyn, D. (2002) · Journal of Endocrinology · doi:10.1677/joe.0.1730081 · Cited by 176 · see citing works

mTOR complex 2 in adipose tissue negatively controls whole-body growth

Cybulski, N., Polak, P., Auwerx, J. H., Rüegg, M. A., & Hall, M. N. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811321106 · Cited by 175 · see citing works

Mechanisms of the depot specificity of peroxisome proliferator-activated receptor γ action on adipose tissue metabolism.

Laplante, M., Festuccia, W. T., Soucy, G., Gélinas, Y., Lalonde, J., Berger, J. P., & Deshaies, Y. (2006) · Diabetes · doi:10.2337/db06-0551 · Cited by 119 · see citing works

Inhibition of ADRP prevents diet-induced insulin resistance

Varela, G. M., Antwi, D. A., Dhir, R. N., Yin, X., Singhal, N. S., Graham, M. J., Crooke, R. M., & Ahima, R. S. (2008) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.90204.2008 · Cited by 111 · see citing works

Central Resistin Induces Hepatic Insulin Resistance via Neuropeptide Y

Singhal, N. S., Lazar, M. A., & Ahima, R. S. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2443-07.2007 · Cited by 95 · see citing works

Improved insulin sensitivity by calorie restriction is associated with reduction of ERK and p70S6K activities in the liver of obese Zucker rats

Zheng, Y., Zhang, W., Pendleton, E., Leng, S.-H., Wu, J., Chen, R., & Sun, X. (2009) · Journal of Endocrinology · doi:10.1677/joe-09-0181 · Cited by 73 · see citing works

Basal adrenergic tone is required for maximal stimulation of rat brown adipose tissue UCP1 expression by chronic PPAR-γ activation

Festuccia, W. T., Blanchard, P.-G., Richard, D., & Deshaies, Y. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00821.2009 · Cited by 59 · see citing works

Pursuing longevity: delay vs elimination of degenerative diseases.

Olshansky, S. J. (1985) · American Journal of Public Health · doi:10.2105/ajph.75.7.754 · Cited by 27 · see citing works

The Hallmarks of Aging

López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works

mTOR Signaling in Growth, Metabolism, and Disease

Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.02.004 · Cited by 7,555 · see citing works

mTOR at the nexus of nutrition, growth, ageing and disease

Liu, G. Y., & Sabatini, D. M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0199-y · Cited by 2,737 · see citing works

Sarcopenia: Aging-Related Loss of Muscle Mass and Function

Larsson, L., Degens, H., Li, M., Salviati, L., Lee, Y. I., Thompson, W., Kirkland, J. L., & Sandri, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00061.2017 · Cited by 1,797 · see citing works

mTOR is a key modulator of ageing and age-related disease

Johnson, S. C., Rabinovitch, P. S., & Kaeberlein, M. (2013) · Nature · doi:10.1038/nature11861 · Cited by 1,676 · see citing works

Branched-chain amino acids in metabolic signalling and insulin resistance

Lynch, C. J., & Adams, S. H. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.171 · Cited by 1,461 · see citing works

Rapamycin: one drug, many effects

Li, J., Kim, S. G., & Blenis, J. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.001 · Cited by 1,287 · see citing works

Cellular senescence: a translational perspective

Kirkland, J. L., & Tchkonia, T. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.04.013 · Cited by 1,013 · see citing works

Metabolic control of autophagy

Galluzzi, L., Pietrocola, F., Levine, B., & Kroemer, G. (2014) · Cell · doi:10.1016/j.cell.2014.11.006 · Cited by 855 · see citing works

Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles

Galluzzi, L., Bravo-San Pedro, J. M., Levine, B., Green, D. R., & Kroemer, G. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.22 · Cited by 842 · see citing works

Targeting the translation machinery in cancer

Bhat, M., Robichaud, N., Hulea, L., Sonenberg, N., Pelletier, J., & Topisirovic, I. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4505 · Cited by 799 · see citing works

Molecular mechanisms of dietary restriction promoting health and longevity

Green, C. L., Lamming, D. W., & Fontana, L. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00411-4 · Cited by 714 · 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

Canonical Nlrp3 Inflammasome Links Systemic Low-Grade Inflammation to Functional Decline in Aging

Youm, Y.-H., Grant, R. W., McCabe, L. R., Albarado, D. C., Nguyen, K. Y., Ravussin, A., Pistell, P., Newman, S., Carter, R., Laque, A., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.010 · Cited by 674 · see citing works

SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans

Blackwell, T. K., Steinbaugh, M. J., Hourihan, J. M., Ewald, C. Y., & Isik, M. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.06.008 · Cited by 622 · see citing works

Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential

Madeo, F., Carmona-Gutierrez, D., Hofer, S. J., & Kroemer, G. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.018 · Cited by 630 · see citing works

mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review

Weichhart, T. (2018) · Gerontology · doi:10.1159/000484629 · Cited by 596 · see citing works

Interventions to slow aging in humans: are we ready?

Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., Curiel, T. J., Cabo, R., Franceschi, C., Gems, D., et al. (2015) · Aging Cell · doi:10.1111/acel.12338 · Cited by 592 · see citing works

Signaling pathways controlling skeletal muscle mass

Egerman, M. A., & Glass, D. J. (2014) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.857291 · Cited by 555 · see citing works

Meta-hallmarks of aging and cancer

López-Otín, C., Pietrocola, F., Roiz-Valle, D., Galluzzi, L., & Kroemer, G. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2022.11.001 · Cited by 529 · 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

The mechanistic target of rapamycin: the grand conducTOR of metabolism and aging

Kennedy, B. K., & Lamming, D. W. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.009 · Cited by 544 · see citing works

The role of cellular senescence in ageing and endocrine disease

Khosla, S., Farr, J. N., Tchkonia, T., & Kirkland, J. L. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0335-y · Cited by 523 · see citing works

Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)

Ristow, M., & Schmeisser, K. (2014) · Dose-Response · doi:10.2203/dose-response.13-035.ristow · Cited by 534 · 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

Transient 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

The quest to slow ageing through drug discovery

Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0067-7 · Cited by 468 · see citing works

Insulin resistance causes inflammation in adipose tissue

Shimobayashi, M., Albert, V., Woelnerhanssen, B., Frei, I. C., Weissenberger, D., Meyer-Gerspach, A. C., Clement, N., Moes, S., Colombi, M., Meier, J. A., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96139 · Cited by 480 · see citing works

mTOR: Role in cancer, metastasis and drug resistance

Murugan, A. K. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.07.003 · Cited by 483 · see citing works

The Autophagy–Lysosomal Pathway in Neurodegeneration: A TFEB Perspective

Martini-Stoica, H., Xu, Y., Ballabio, A., & Zheng, H. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.02.002 · Cited by 436 · see citing works

Targeting the biology of aging with mTOR inhibitors

Mannick, J. B., & Lamming, D. W. (2023) · Nature Aging · doi:10.1038/s43587-023-00416-y · Cited by 372 · see citing works

Inhibition of the mTORC Pathway in the Antiphospholipid Syndrome

Canaud, G., Bienaimé, F., Tabarin, F., Bataillon, G., Seilhean, D., Noël, L.-H., Dragon-Durey, M.-A., Snanoudj, R., Friedlander, G., Halbwachs-Mecarelli, L., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1312890 · Cited by 355 · see citing works

The Search for Antiaging Interventions: From Elixirs to Fasting Regimens

de Cabo, R., Carmona-Gutierrez, D., Bernier, M., Hall, M. N., & Madeo, F. (2014) · Cell · doi:10.1016/j.cell.2014.05.031 · Cited by 345 · see citing works

Signalling pathways regulating muscle mass in ageing skeletal muscle. The role of the IGF1-Akt-mTOR-FoxO pathway

Sandri, M., Barberi, L., Bijlsma, A. Y., Blaauw, B., Dyar, K. A., Milan, G., Mammucari, C., Meskers, C. G. M., Pallafacchina, G., Paoli, A., et al. (2013) · Biogerontology · doi:10.1007/s10522-013-9432-9 · Cited by 340 · see citing works

Animal models of aging research: implications for human aging and age-related diseases

Mitchell, S. J., Scheibye-Knudsen, M., Longo, D. L., & de Cabo, R. (2015) · Annual Review of Animal Biosciences · doi:10.1146/annurev-animal-022114-110829 · Cited by 328 · see citing works

Repairing mitochondrial dysfunction in disease

Sorrentino, V., Menzies, K. J., & Auwerx, J. (2018) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104908 · Cited by 337 · see citing works

Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes

Shivaswamy, V., Boerner, B., & Larsen, J. (2016) · Endocrine Reviews · doi:10.1210/er.2015-1084 · Cited by 328 · see citing works

The metabolic regulation of aging

Finkel, T. (2015) · Nature Medicine · doi:10.1038/nm.3998 · Cited by 325 · see citing works

Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration

Querfurth, H., & Lee, H.-K. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00428-5 · Cited by 288 · see citing works

mTOR signaling in cellular and organismal energetics

Albert, V., & Hall, M. N. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2014.12.001 · Cited by 304 · see citing works

Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3

Lee, J. H., Budanov, A. V., Talukdar, S., Park, E. J., Park, H. L., Park, H.-W., Bandyopadhyay, G., Li, N., Aghajan, M., Jang, I., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.004 · Cited by 295 · see citing works

The Genetics of Aging: A Vertebrate Perspective

Singh, P. P., Demmitt, B. A., Nath, R. D., & Brunet, A. (2019) · Cell · doi:10.1016/j.cell.2019.02.038 · Cited by 259 · see citing works

A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan

Mohammed, I., Hollenberg, M. D., Ding, H., & Triggle, C. R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.718942 · Cited by 278 · see citing works

Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium

Pentinmikko, N., Iqbal, S., Mana, M., Andersson, S., Cognetta, A. B., Suciu, R. M., Roper, J., Luopajärvi, K., Markelin, E., Gopalakrishnan, S., et al. (2019) · Nature · doi:10.1038/s41586-019-1383-0 · Cited by 271 · see citing works

Autophagy in Cardiovascular Aging

Abdellatif, M., Sedej, S., Carmona-Gutierrez, D., Madeo, F., & Kroemer, G. (2018) · Circulation Research · doi:10.1161/circresaha.118.312208 · Cited by 239 · see citing works

Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling

Peng, M., Yin, N., & Li, M. O. (2014) · Cell · doi:10.1016/j.cell.2014.08.038 · Cited by 220 · see citing works

mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging

Perl, A. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12756 · Cited by 218 · see citing works

Duration of Rapamycin Treatment Has Differential Effects on Metabolism in Mice

Fang, Y., Westbrook, R., Hill, C., Boparai, R. K., Arum, O., Spong, A., Wang, F., Javors, M. A., Chen, J., Sun, L. Y., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.02.008 · Cited by 195 · see citing works

Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system

Arriola 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

Protein synthesis and quality control in aging

Anisimova, A. S., Alexandrov, A. I., Makarova, N. E., Gladyshev, V. N., & Dmitriev, S. E. (2018) · Aging · doi:10.18632/aging.101721 · Cited by 172 · see citing works

Clinical strategies and animal models for developing senolytic agents

Kirkland, J. L., & Tchkonia, T. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2014.10.012 · Cited by 168 · see citing works

Myelination and mTOR

Figlia, G., Gerber, D., & Suter, U. (2018) · Glia · doi:10.1002/glia.23273 · Cited by 165 · see citing works

Signaling networks determining life span

Riera, C. E., Merkwirth, C., De Magalhaes Filho, C. D., & Dillin, A. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014451 · Cited by 161 · see citing works

MicroRNA 33 Regulates Glucose Metabolism

Ramírez, C. M., Goedeke, L., Rotllan, N., Yoon, J.-H., Cirera-Salinas, D., Mattison, J. A., Suárez, Y., de Cabo, R., Gorospe, M., & Fernández-Hernando, C. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00016-13 · Cited by 154 · see citing works

Differential response of skeletal muscles to mTORC1 signaling during atrophy and hypertrophy

Bentzinger, C. F., Lin, S., Romanino, K., Castets, P., Guridi, M., Summermatter, S., Handschin, C., Tintignac, L. A., Hall, M. N., & Rüegg, M. A. (2013) · Skeletal Muscle · doi:10.1186/2044-5040-3-6 · Cited by 153 · see citing works

Tipping the metabolic scales towards increased longevity in mammals

Riera, C. E., & Dillin, A. (2015) · Nature Cell Biology · doi:10.1038/ncb3107 · Cited by 153 · see citing works

Large FK506-binding proteins shape the pharmacology of rapamycin

März, A. M., Fabian, A.-K., Kozany, C., Bracher, A., & Hausch, F. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00678-12 · Cited by 141 · see citing works

Cyclin G1 and TASCC regulate kidney epithelial cell G ₂ -M arrest and fibrotic maladaptive repair

Canaud, G., Brooks, C. R., Kishi, S., Taguchi, K., Nishimura, K., Magassa, S., Scott, A., Hsiao, L.-L., Ichimura, T., Terzi, F., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aav4754 · Cited by 139 · see citing works

Disturbed glucose and pyruvate metabolism in glaucoma with neuroprotection by pyruvate or rapamycin

Harder, J. M., Guymer, C., Wood, J. P. M., Daskalaki, E., Chidlow, G., Zhang, C., Balasubramanian, R., Cardozo, B. H., Foxworth, N. E., Deering, K. E., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2014213117 · Cited by 127 · see citing works

Role of mTORC1 in mechanically induced increases in translation and skeletal muscle mass

Goodman, C. A. (2019) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01011.2018 · Cited by 133 · see citing works

Insulin signalling promotes dendrite and synapse regeneration and restores circuit function after axonal injury

Agostinone, J., Alarcon-Martinez, L., Gamlin, C., Yu, W.-Q., Wong, R. O. L., & Di Polo, A. (2018) · Brain · doi:10.1093/brain/awy142 · Cited by 124 · see citing works

<scp>TOR</scp>‐mediated regulation of metabolism in aging

Antikainen, H., Driscoll, M., Haspel, G., & Dobrowolski, R. (2017) · Aging Cell · doi:10.1111/acel.12689 · Cited by 122 · see citing works

Rapamycin transiently induces mitochondrial remodeling to reprogram energy metabolism in old hearts

Chiao, Y. A., Kolwicz, S. C., Basisty, N., Gagnidze, A., Zhang, J., Gu, H., Djukovic, D., Beyer, R. P., Raftery, D., MacCoss, M., et al. (2016) · Aging · doi:10.18632/aging.100881 · Cited by 128 · see citing works

Drugs that modulate aging: the promising yet difficult path ahead

Kennedy, B. K., & Pennypacker, J. K. (2014) · Translational research · doi:10.1016/j.trsl.2013.11.007 · Cited by 127 · see citing works

Long-lasting geroprotection from brief rapamycin treatment in early adulthood by persistently increased intestinal autophagy

Juricic, P., Lu, Y.-X., Leech, T., Drews, L. F., Paulitz, J., Lu, J., Nespital, T., Azami, S., Regan, J. C., Funk, E., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00278-w · Cited by 118 · see citing works

Mouse Models to Disentangle the Hallmarks of Human Aging

Folgueras, A. R., Freitas-Rodríguez, S., Velasco, G., & López-Otín, C. (2018) · Circulation Research · doi:10.1161/circresaha.118.312204 · Cited by 113 · see citing works

mTOR complex 1: a key player in neuroadaptations induced by drugs of abuse

Neasta, J., Barak, S., Hamida, S. B., & Ron, D. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12725 · Cited by 114 · see citing works

Impact of Senescent Cell Subtypes on Tissue Dysfunction and Repair: Importance and Research Questions

Tripathi, U., Misra, A., Tchkonia, T., & Kirkland, J. L. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111548 · Cited by 104 · see citing works

Unraveling female reproductive senescence to enhance healthy longevity

Dong, L., Teh, D. B. L., Kennedy, B. K., & Huang, Z. (2023) · Cell Research · doi:10.1038/s41422-022-00718-7 · Cited by 101 · see citing works

<scp>mTOR</scp> signaling and Alzheimer's disease: What we know and where we are?

Davoody, S., Asgari Taei, A., Khodabakhsh, P., & Dargahi, L. (2024) · CNS Neuroscience &amp; Therapeutics · doi:10.1111/cns.14463 · Cited by 96 · see citing works

The Role of Rapamycin in Healthspan Extension via the Delay of Organ Aging

Zhang, Y., Zhang, J., & Wang, S. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101376 · Cited by 92 · see citing works

Assessment of mitochondrial biogenesis and mTORC1 signaling during chronic rapamycin feeding in male and female mice

Drake, J. C., Peelor, F. F., Biela, L. M., Watkins, M. K., Miller, R. A., Hamilton, K. L., & Miller, B. F. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt047 · Cited by 87 · see citing works

Translating the Science of Aging into Therapeutic Interventions

Kirkland, J. L. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a025908 · Cited by 78 · see citing works

Increased mTOR activation in idiopathic multicentric Castleman disease

Arenas, D. J., Floess, K., Kobrin, D., Pai, R.-A. L., Srkalovic, M. B., Tamakloe, M.-A., Rasheed, R., Ziglar, J., Khor, J., Parente, S. A. T., et al. (2020) · Blood · doi:10.1182/blood.2019002792 · Cited by 83 · see citing works

Fasting and rapamycin: diabetes versus benevolent glucose intolerance

Blagosklonny, M. V. (2019) · Cell Death &amp; Disease · doi:10.1038/s41419-019-1822-8 · Cited by 74 · see citing works

The role of the TOR pathway in mediating the link between nutrition and longevity

Lushchak, O., Strilbytska, O., Piskovatska, V., Storey, K. B., Koliada, A., & Vaiserman, A. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.03.005 · Cited by 73 · see citing works

AMPK hyperactivation promotes dendrite retraction, synaptic loss, and neuronal dysfunction in glaucoma

Belforte, N., Agostinone, J., Alarcon-Martinez, L., Villafranca-Baughman, D., Dotigny, F., Cueva Vargas, J. L., & Di Polo, A. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00466-z · Cited by 67 · see citing works

Restriction of dietary protein decreases mTORC1 in tumors and somatic tissues of a tumor-bearing mouse xenograft model

Lamming, D. W., Cummings, N. E., Rastelli, A. L., Gao, F., Cava, E., Bertozzi, B., Spelta, F., Pili, R., & Fontana, L. (2015) · Oncotarget · doi:10.18632/oncotarget.5180 · Cited by 69 · see citing works

Rapamycin-induced metabolic defects are reversible in both lean and obese mice

Liu, Y., Diaz, V., Fernandez, E., Strong, R., Ye, L., Baur, J. A., Lamming, D. W., Richardson, A., & Salmon, A. B. (2014) · Aging · doi:10.18632/aging.100688 · Cited by 68 · 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

mTOR regulates the expression of DNA damage response enzymes in long‐lived Snell dwarf, GHRKO, and PAPPA‐KO mice

Dominick, G., Bowman, J., Li, X., Miller, R. A., & Garcia, G. G. (2017) · Aging Cell · doi:10.1111/acel.12525 · Cited by 62 · see citing works

mTORC2 (Rictor) in Alzheimer’s Disease and Reversal of Amyloid-β Expression-Induced Insulin Resistance and Toxicity in Rat Primary Cortical Neurons

Lee, H.-K., Kwon, B., Lemere, C. A., de la Monte, S., Itamura, K., Ha, A. Y., & Querfurth, H. W. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-161029 · Cited by 57 · see citing works

Potential therapeutic effects of the MTOR inhibitors for preventing ageing and progeria-related disorders

Evangelisti, C., Cenni, V., & Lattanzi, G. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12928 · Cited by 53 · see citing works

Differential localization and anabolic responsiveness of mTOR complexes in human skeletal muscle in response to feeding and exercise

Hodson, N., McGlory, C., Oikawa, S. Y., Jeromson, S., Song, Z., Rüegg, M. A., Hamilton, D. L., Phillips, S. M., & Philp, A. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00176.2017 · Cited by 51 · see citing works

Anti-tumor Effects of Everolimus and Metformin Are Complementary and Glucose-dependent in Breast Cancer Cells

Ariaans, G., Jalving, M., Vries, E. G. E. D., & Jong, S. D. (2017) · BMC Cancer · doi:10.1186/s12885-017-3230-8 · Cited by 51 · see citing works

Therapeutic Use of mTOR Inhibitors in Renal Diseases: Advances, Drawbacks, and Challenges

Viana, S. D., Reis, F., & Alves, R. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/3693625 · Cited by 48 · see citing works

Insulin Regulation of Hepatic Lipid Homeostasis

Uehara, K., Santoleri, D., Whitlock, A. E. G., & Titchenell, P. M. (2023) · Comprehensive Physiology · doi:10.1002/cphy.c220015 · Cited by 49 · see citing works

T cell receptor-mediated activation is a potent inducer of macroautophagy in human CD8(+)CD28(+) T cells but not in CD8(+)CD28(-) T cells

Arnold, C. R., Pritz, T., Brunner, S., Knabb, C., Salvenmoser, W., Holzwarth, B., Thedieck, K., & Grubeck-Loebenstein, B. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.01.018 · Cited by 42 · see citing works

Metabolic reprogramming: a bridge between aging and tumorigenesis

Drapela, S., Ilter, D., & Gomes, A. P. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13261 · Cited by 41 · see citing works

AKT/mTORC pathway in antiphospholipid-related vasculopathy: a new player in the game

Canaud, G., Legendre, C., & Terzi, F. (2015) · Lupus · doi:10.1177/0961203315569336 · Cited by 32 · see citing works

Paradoxical effect of rapamycin on inflammatory stress-induced insulin resistance in vitro and in vivo

Yang, P., Zhao, Y., Zhao, L., Yuan, J., Chen, Y., Varghese, Z., Moorhead, J. F., Chen, Y., & Ruan, X. Z. (2015) · Scientific Reports · doi:10.1038/srep14959 · Cited by 21 · see citing works

The significance of caloric restriction mimetics as anti-aging drugs

Nassar, K., El-mekawey, D., Elmasry, A. E., Refaey, M. S., El-Sayed Ghoneim, M., & Elshaier, Y. A. M. M. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2023.149354 · Cited by 16 · see citing works

Therapeutic Manipulation of Ageing: Repurposing Old Dogs and Discovering New Tricks

Mallikarjun, V., & Swift, J. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.11.020 · Cited by 14 · see citing works

Rapamycin impacts positively on longevity, despite glucose intolerance induction

Piguet, A., Martins, P. J. F., & Kozma, S. C. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.06.038 · Cited by 4 · see citing works

Effects of rapamycin on growth hormone receptor knockout mice

Fang, Y., Hill, C. M., Darcy, J., Reyes‐Ordoñez, A., Arauz, E. J., McFadden, S., Zhang, C., Osland, J. M., Gao, J., Zhang, T., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1717065115 · Cited by 46 · see citing works

Dietary induced insulin resistance is independent of mammalian target of rapamycin complex 1 (mTORC1) activity in skeletal muscle of mice

Phelps, C., Berk, E. Z., & Reynolds, T. H. (2008) · The FASEB Journal · doi:10.1096/fasebj.22.1_supplement.1226.25

Alternative Rapamycin Treatment Regimens Mitigate the Impact of Rapamycin on Glucose Homeostasis and the Immune System, and Extends Lifespan

Apelo, S. I. A., Pumper, C. P., Baar, E. L., Cummings, N., Brar, H., Kimple, M., Lamming, D. W., & Jc, N. (2016) · Journal of Investigative Medicine · doi:10.1136/jim-2016-000120.45 · Cited by 1 · see citing works

P101The effect of rapamycin in cardiac mTORC2-deficient mice under pressure overload conditions

Brink, M., Xu, L., & Morandi, C. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu082.43