An Ancient, Unified Mechanism for Metformin Growth Inhibition in C. Elegans and Cancer
Open accessAbstract
Metformin has utility in cancer prevention and treatment, though the mechanisms for these effects remain elusive. Through genetic screening in C. elegans, we uncover two metformin response elements: the nuclear pore complex (NPC) and acyl-CoA dehydrogenase family member-10 (ACAD10). We demonstrate that biguanides inhibit growth by inhibiting mitochondrial respiratory capacity, which restrains transit of the RagA-RagC GTPase heterodimer through the NPC. Nuclear exclusion renders RagC incapable of gaining the GDP-bound state necessary to stimulate mTORC1. Biguanide-induced inactivation of mTORC1 subsequently inhibits growth through transcriptional induction of ACAD10. This ancient metformin response pathway is conserved from worms to humans. Both restricted nuclear pore transit and upregulation of ACAD10 are required for biguanides to reduce viability in melanoma and pancreatic cancer cells, and to extend C. elegans lifespan. This pathway provides a unified mechanism by which metformin kills cancer cells and extends lifespan, and illuminates potential cancer targets. PAPERCLIP.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In C. elegans the beneficial effects of metformin on lifespan are, at least in part, argued to be mediated through changing the microbiome and modifying microbial folate and methionine metabolism and potentially due to an anti-oxidant action via transcription factors SKN-1/Nrf2, a requirement for AMPK and the upstream serine-threonine kinase LKB1.
“In C. elegans the beneficial effects of metformin on lifespan are, at least in part, argued to be mediated through changing the microbiome and modifying microbial folate and methionine metabolism and potentially due to an anti-oxidant action via transcription factors, SKN-1/Nrf2, a requirement for AMPK and the upstream serine-threonine kinase, liver kinase B1 (LKB1) (67, 71, 86).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [86]
In C. elegans studies, very high concentrations of metformin, from 10 to 150 mM, were used, and are equivalent to a dose in humans of approximately 5 kg/day.
“However, in these studies with C. elegans, very high concentrations of metformin, from 10 to 150 mM, were used (67, 86), and are the equivalent to a dose in humans of approximately 5 kg/day.”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [86]
Metformin exerts many of its growth inhibitory and anti-neoplastic effects through the nuclear pore complex and ACAD10.
“Metformin exerts many of its growth inhibitory and anti-neoplastic effects through the nuclear pore complex and acyl-CoA dehydrogensase family member-10 (ACAD10)(278).”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [278]
Nucleocytoplasmic shuttling regulates mTORC activity, and this effect can be reversed by RNA silencing.
“Nucleocytoplasmic shuttling regulates mTORC activity, an effect that can be reversed by RNA silencing.”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [278]
By preventing access to the nucleus, RagC becomes incapable of stimulating mTORC1 and therefore stimulates cellular growth.
“By preventing access to the nucleus, RagC becomes incapable of stimulating mTORC1 and, therefore, stimulates cellular growth (Figure 12)(278).”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [278]
Biguanides inhibit growth by suppressing mitochondrial respiration, which limits the transit of the RagA-RagC GTPase heterodimer through the nuclear pore complex.
“Biguanides inhibit growth by suppressing mitochondrial respiration, which limits the transit of the complex RagA-RagC GTPase heterodimer through the nuclear pore complex(278).”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [278]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
THE GENETICS OF CAENORHABDITIS ELEGANS
Brenner, S. (1974) · Genetics · doi:10.1093/genetics/77.1.71 · Cited by 14,984 · see citing works
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652 · 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
Metformin and reduced risk of cancer in diabetic patients
Evans, J. M. M., Donnelly, L. A., Emslie-Smith, A. M., Alessi, D. R., & Morris, A. D. (2005) · BMJ · doi:10.1136/bmj.38415.708634.f7 · Cited by 2,388 · see citing works
OWEN, M. R., DORAN, E., & HALESTRAP, A. P. (2000) · Biochemical Journal · doi:10.1042/bj3480607 · Cited by 2,157 · see citing works
TOR, a central controller of cell growth.
Schmelzle, T., & Hall, M. (2000) · Cell · doi:10.1016/s0092-8674(00)00117-3 · Cited by 2,044 · 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
Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase
Madiraju, A. K., Erion, D. M., Rahimi, Y., Zhang, X.-M., Braddock, D. T., Albright, R. A., Prigaro, B. J., Wood, J. L., Bhanot, S., MacDonald, M. J., et al. (2014) · Nature · doi:10.1038/nature13270 · Cited by 1,284 · see citing works
Regulation of the mTOR Complex 1 Pathway by Nutrients, Growth Factors, and Stress
Sengupta, S., Peterson, T. R., & Sabatini, D. M. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.026 · Cited by 1,234 · see citing works
Foretz, M., Hébrard, S., Leclerc, J., Zarrinpashneh, E., Soty, M., Mithieux, G., Sakamoto, K., Andreelli, F., & Viollet, B. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40671 · Cited by 1,181 · see citing works
Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis
Wheaton, W. W., Weinberg, S. E., Hamanaka, R. B., Soberanes, S., Sullivan, L. B., Anso, E., Glasauer, A., Dufour, E., Mutlu, G. M., Budigner, G. S., et al. (2014) · eLife · doi:10.7554/elife.02242 · Cited by 1,105 · see citing works
Metformin as a tool to target aging
Barzilai, N., Crandall, J. P., Kritchevsky, S. B., & Espeland, M. A. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.011 · Cited by 1,096 · see citing works
Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism
Cabreiro, F., Au, C., Leung, K.-Y., Vergara-Irigaray, N., Cochemé, H. M., Noori, T., Weinkove, D., Schuster, E., Greene, N. D. E., & Gems, D. (2013) · Cell · doi:10.1016/j.cell.2013.02.035 · Cited by 967 · see citing works
Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner
Kalender, A., Selvaraj, A., Kim, S. Y., Gulati, P., Brûlé, S., Viollet, B., Kemp, B. E., Bardeesy, N., Dennis, P., Schlager, J. J., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.03.014 · Cited by 889 · see citing works
Analysis and prediction of leucine-rich nuclear export signals
COUR, T. L., Kiemer, L., Mølgaard, A., Gupta, R., Skriver, K., & Brunak, S. (2004) · Protein Engineering Design and Selection · doi:10.1093/protein/gzh062 · Cited by 752 · see citing works
Onken, B., & Driscoll, M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008758 · Cited by 671 · 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
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
D'Angelo, M. A., Raices, M., Panowski, S. H., & Hetzer, M. W. (2009) · Cell · doi:10.1016/j.cell.2008.11.037 · Cited by 565 · see citing works
Where is mTOR and what is it doing there?
Betz, C., & Hall, M. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201306041 · Cited by 529 · see citing works
REAP: A two minute cell fractionation method
Suzuki, K., Bose, P., Leong-Quong, R. Y. Y., Fujita, D. J., & Riabowol, K. T. (2010) · BMC Research Notes · doi:10.1186/1756-0500-3-294 · Cited by 474 · see citing works
Han, S. K., Lee, D.-Y., Lee, H., Kim, D., Son, H. G., Yang, J., Lee, S., & Kim, S. (2016) · Oncotarget · doi:10.18632/oncotarget.11269 · Cited by 468 · see citing works
Simple rules for passive diffusion through the nuclear pore complex
Timney, B. L., Raveh, B., Mironska, R., Trivedi, J. M., Kim, S. J., Russel, D., Wente, S. R., Šali, A., & Rout, M. P. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201601004 · Cited by 461 · see citing works
Kordes, S., Pollak, M., Zwinderman, A. H., Mathôt, R. A. A., Weterman, M. J., Beeker, A., Punt, C. J. A., Richel, D. J., & Wilmink, J. W. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00027-3 · Cited by 387 · see citing works
Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2
De Haes, W., Frooninckx, L., Van Assche, R., Smolders, A., Depuydt, G., Billen, J., Braeckman, B. P., Schoofs, L., & Temmerman, L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321776111 · Cited by 355 · see citing works
Watson, E. V., MacNeil, L. T., Ritter, A. D., Yilmaz, L. S., Rosebrock, A. P., Caudy, A. A., & Walhout, A. J. M. (2014) · Cell · doi:10.1016/j.cell.2014.01.047 · Cited by 269 · see citing works
Transient nuclear envelope rupturing during interphase in human cancer cells
Vargas, J. D., Hatch, E. M., Anderson, D. J., & Hetzer, M. W. (2012) · Nucleus · doi:10.4161/nucl.18954 · Cited by 263 · see citing works
Phenformin enhances the therapeutic benefit of BRAF V600E inhibition in melanoma
Yuan, P., Ito, K., Pérez‐Lorenzo, R., Guzzo, C. D., Lee, J. H., Shen, C., Bosenberg, M., McMahon, M., Cantley, L. C., & Zheng, B. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1317577110 · Cited by 218 · see citing works
Self-citationSystematic analysis of barrier‐forming FG hydrogels from Xenopus nuclear pore complexes
Labokha, A. A., Gradmann, S., Frey, S., Hülsmann, B. B., Urlaub, H., Baldus, M., & Görlich, D. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.302 · Cited by 213 · see citing works
Lipid-mediated regulation of SKN-1/Nrf in response to germ cell absence
Steinbaugh, M. J., Narasimhan, S. D., Robida-Stubbs, S., Mazzeo, L. E. M., Dreyfuss, J. M., Hourihan, J. M., Raghavan, P., Operaña, T. N., Esmaillie, R., & Blackwell, T. K. (2015) · eLife · doi:10.7554/elife.07836 · Cited by 213 · see citing works
Cheng, G., Zielonka, J., Ouari, O., López, M., McAllister, D. M., Boyle, K., Barrios, C. S., Weber, J. J., Johnson, B. D., Hardy, M., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2534 · Cited by 212 · see citing works
Metformin Antagonizes Cancer Cell Proliferation by Suppressing Mitochondrial-Dependent Biosynthesis
Griss, T., Vincent, E. E., Egnatchik, R. A., Chen, J., Ma, E. H., Faubert, B., Viollet, B., DeBerardinis, R. J., & Jones, R. G. (2015) · PLoS Biology · doi:10.1371/journal.pbio.1002309 · Cited by 211 · see citing works
Kim, J. E., & Chen, J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.011511898 · Cited by 200 · see citing works
Distinct perturbation of the translatome by the antidiabetic drug metformin
Larsson, O. S., Morita, M., Topisirović, I., Alain, T., Blouin, M., Pollak, M., & Sonenberg, N. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201689109 · Cited by 199 · see citing works
Galy, V., Mattaj, I. W., & Askjaer, P. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-04-0237 · Cited by 186 · see citing works
Mitochondrial SKN-1/Nrf Mediates a Conserved Starvation Response
Paek, J., Lo, J. Y., Narasimhan, S. D., Nguyen, T. N., Glover-Cutter, K. M., Robida-Stubbs, S., Suzuki, T., Yamamoto, M. P., Blackwell, T. K., & Curran, S. P. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.09.007 · Cited by 178 · see citing works
Yuan, M., Pino, E. C., Wu, L., Kacergis, M. C., & Soukas, A. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.386854 · Cited by 154 · see citing works
Self-citationDAF-16/FOXO targets genes that regulate tumor growth in Caenorhabditis elegans
Pinkston-Gosse, J., & Kenyon, C. J. (2007) · Nature Genetics · doi:10.1038/ng.2007.1 · Cited by 154 · see citing works
Cancer and the Nuclear Pore Complex
Simon, D. N., & Rout, M. P. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4899-8032-8_13 · Cited by 121 · see citing works
RagA is a functional homologue of S. cerevisiae Gtr1p involved in the Ran/Gsp1-GTPase pathway
Hirose, E., Nakashima, N., Sekiguchi, T., & Nishimoto, T. (1998) · Journal of Cell Science · doi:10.1242/jcs.111.1.11 · Cited by 89 · see citing works
ATP-Induced Shape Change of Nuclear Pores Visualized with the Atomic Force Microscope
RAKOWSKA, A., Danker, T., Schneider, S. W., & Oberleithner, H. (1998) · The Journal of Membrane Biology · doi:10.1007/s002329900377 · Cited by 82 · see citing works
Biochemical and High Throughput Microscopic Assessment of Fat Mass in Caenorhabditis Elegans
Pino, E. C., Webster, C. M., Carr, C. E., & Soukas, A. A. (2013) · Journal of Visualized Experiments · doi:10.3791/50180 · Cited by 74 · see citing works
Self-citationOshiro, N., Rapley, J., & Avruch, J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.528505 · Cited by 59 · see citing works
Altering nuclear pore complex function impacts longevity and mitochondrial function in S. cerevisiae
Lord, C. L., Timney, B. L., Rout, M. P., & Wente, S. R. (2015) · The Journal of Cell Biology · doi:10.1083/jcb.201412024 · Cited by 58 · see citing works
MAGIC Investigators, Bian, L., Hanson, R. L., Muller, Y. L., Ma, L., Kobes, S., Knowler, W. C., BOGARDUS, C., & Baier, L. J. (2010) · Diabetologia · doi:10.1007/s00125-010-1695-y · Cited by 43 · see citing works
Kinoshita, Y., Kalir, T., Rahaman, J., Dottino, P., & Kohtz, D. S. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.09.024 · Cited by 40 · see citing works
Prachař, J. (2003) · PubMed · Cited by 27 · see citing works
The expanding relevance of nuclear mTOR in carcinogenesis
Back, J. H., & Kim, A. L. (2011) · Cell Cycle · doi:10.4161/cc.10.22.18329 · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The mechanisms of action of metformin
Rena, G., Hardie, D. G., & Pearson, E. R. (2017) · Diabetologia · doi:10.1007/s00125-017-4342-z · Cited by 2,287 · see citing works
Spermidine in health and disease
Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G. (2018) · Science · doi:10.1126/science.aan2788 · Cited by 1,154 · see citing works
Benefits of Metformin in Attenuating the Hallmarks of Aging
Kulkarni, A. S., Gubbi, S., & Barzilai, N. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.04.001 · Cited by 766 · see citing works
Low-dose metformin targets the lysosomal AMPK pathway through PEN2
Ma, T., Tian, X., Zhang, B., Li, M., Wang, Y., Yang, C., Wu, J., Wei, X., Qu, Q., Yu, Y., et al. (2022) · Nature · doi:10.1038/s41586-022-04431-8 · Cited by 644 · see citing works
Self-citationMetformin: Mechanisms in Human Obesity and Weight Loss
Yerevanian, A., & Soukas, A. A. (2019) · Current Obesity Reports · doi:10.1007/s13679-019-00335-3 · Cited by 414 · see citing works
Self-citationmTOR-dependent phosphorylation controls TFEB nuclear export
Napolitano, G., Esposito, A., Choi, H., Matarese, M., Benedetti, V., Malta, C. D., Monfregola, J., Medina, D. L., Lippincott‐Schwartz, J., & Ballabio, A. (2018) · Nature Communications · doi:10.1038/s41467-018-05862-6 · Cited by 408 · see citing works
Metformin: a review of its potential indications
Wang, Y., He, S., Feng, X., Cheng, J. Q., Luo, Y.-T., Tian, L., & Huang, Q. (2017) · Drug Design Development and Therapy · doi:10.2147/dddt.s141675 · Cited by 324 · see citing works
Role of mitochondria in the mechanism(s) of action of metformin
Vial, G., Detaille, D., & Guigas, B. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00294 · Cited by 303 · see citing works
Metformin as an Anticancer Agent
Vancura, A., Bu, P., Bhagwat, M., Zeng, J., & Vancurova, I. (2018) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2018.07.006 · Cited by 274 · see citing works
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
Host-microbe-drug-nutrient screen identifies bacterial effectors of metformin therapy
Pryor, R., Norvaisas, P., Marinos, G., Best, L., Thingholm, L. B., Quintaneiro, L. M., De Haes, W., Esser, D., Waschina, S., Lujan, C., et al. (2019) · Cell · doi:10.1016/j.cell.2019.08.003 · Cited by 274 · see citing works
Metformin as Anti-Aging Therapy: Is It for Everyone?
Soukas, A. A., Hao, H., & Wu, L. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.07.015 · Cited by 260 · see citing works
Self-citationRomero, R., Erez, O., Hüttemann, M., Maymon, E., Panaitescu, B., Conde-Agudelo, A., Pacora, P., Yoon, B. H., & Grossman, L. I. (2017) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2017.06.003 · Cited by 253 · see citing works
Inflammageing and metaflammation: The yin and yang of type 2 diabetes
Prattichizzo, F., Nigris, V. D., Spiga, R., Mancuso, E., Sala, L. L., Antonicelli, R., Testa, R., Procopio, A. D., Olivieri, F., & Ceriello, A. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.10.003 · Cited by 249 · see citing works
Han, H., Hou, Y., Chen, X., Zhang, P., Kang, M., Jin, Q., Ji, J., & Gao, M. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c00650 · Cited by 232 · see citing works
Metformin extends C. elegans lifespan through lysosomal pathway
Chen, J., Ou, Y., Li, Y., Hu, S., Shao, L.-W., & Liu, Y. (2017) · eLife · doi:10.7554/elife.31268 · Cited by 202 · see citing works
Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing
Hua, Y., Zheng, Y., Yao, Y., Jia, R., Ge, S., & Zhuang, A. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04263-8 · Cited by 207 · see citing works
The lysosome: a crucial hub for AMPK and mTORC1 signalling.
Carroll, B., & Dunlop, E. (2017) · Biochemical Journal · doi:10.1042/bcj20160780 · Cited by 173 · see citing works
Li, B., Zhou, P., Xu, K., Chen, T., Jiao, J., Wei, H., Yang, X., Xu, W., Wan, W., & Xiao, J. (2019) · International Journal of Biological Sciences · doi:10.7150/ijbs.33787 · Cited by 194 · see citing works
Fang, J., Yang, J., Wu, X., Zhang, G., Li, T., Wang, X., Zhang, H., Wang, C., Liu, G., & Wang, L. (2018) · Aging Cell · doi:10.1111/acel.12765 · Cited by 179 · see citing works
Menegazzo, L., Scattolini, V., Cappellari, R., Bonora, B. M., Albiero, M., Bortolozzi, M., Romanato, F., Ceolotto, G., de Kreutzeberg, S. V., Avogaro, A., et al. (2018) · Acta Diabetologica · doi:10.1007/s00592-018-1129-8 · Cited by 162 · see citing works
Karnewar, S., Neeli, P. K., Panuganti, D., Kotagiri, S., Mallappa, S., Jain, N., Jerald, M. K., & Kotamraju, S. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.01.018 · Cited by 161 · see citing works
Anticancer Activity of Metformin: A Systematic Review of the Literature
Aljofan, M., & Riethmacher, D. (2019) · Future Science OA · doi:10.2144/fsoa-2019-0053 · Cited by 160 · see citing works
Zhang, Z., Li, F., Tian, Y., Cao, L., Gao, Q., Zhang, C., Zhang, K., Shen, C., Ping, Y., Maimela, N. R., et al. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1901213 · Cited by 159 · see citing works
TOR Signaling in Caenorhabditis elegans Development, Metabolism, and Aging
Blackwell, T., Sewell, A. K., Wu, Z.-Y., & Han, M. (2019) · Genetics · doi:10.1534/genetics.119.302504 · Cited by 145 · see citing works
Cai, T., Ye, S., Liu, Y.-N., He, J., Chen, Q.-Y., Mai, H., Zhang, C.-X., Cui, J., Zhang, X.-S., Busson, P., et al. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006503 · Cited by 138 · see citing works
Metformin use in pregnancy: promises and uncertainties
Lindsay, R. S., & Loeken, M. R. (2017) · Diabetologia · doi:10.1007/s00125-017-4351-y · Cited by 129 · see citing works
Molecular Mechanisms of Metformin for Diabetes and Cancer Treatment
Li, M., Li, X., Zhang, H., & Lü, Y. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01039 · Cited by 121 · see citing works
Self-citationLithocholic acid binds TULP3 to activate sirtuins and AMPK to slow down ageing
Qu, Q., Chen, Y., Wang, Y., Wang, W., Long, S., Yang, H.-Y., Wu, J., Li, M., Tian, X., Wei, X., et al. (2024) · Nature · doi:10.1038/s41586-024-08348-2 · Cited by 115 · see citing works
Self-citationPrattichizzo, F., Giuliani, A., Mensa’, E., Sabbatinelli, J., Nigris, V. D., Rippo, M. R., Sala, L. L., Procopio, A. D., Olivieri, F., & Ceriello, A. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.10.003 · Cited by 111 · see citing works
Lithocholic acid phenocopies anti-ageing effects of calorie restriction
Qu, Q., Chen, Y., Wang, Y., Long, S., Wang, W., Yang, H.-Y., Li, M., Tian, X., Wei, X., Liu, Y., et al. (2024) · Nature · doi:10.1038/s41586-024-08329-5 · Cited by 116 · see citing works
Self-citationDrug discovery: Insights from the invertebrate Caenorhabditis elegans
Giunti, S., Andersen, N., Rayes, D., & Rosa, M. J. D. (2021) · Pharmacology Research & Perspectives · doi:10.1002/prp2.721 · Cited by 102 · see citing works
Non-Small-Cell Lung Cancer Signaling Pathways, Metabolism, and PD-1/PD-L1 Antibodies
Santarpía, M., Aguilar, A., CHAIB-OUKADOUR, I., Cardona, A. F., Fancelli, S., Laguía, F., Bracht, J. W. P., Cao, P., Molina‐Vila, M. Á., Karachaliou, N., et al. (2020) · Cancers · doi:10.3390/cancers12061475 · Cited by 100 · see citing works
The aldolase inhibitor aldometanib mimics glucose starvation to activate lysosomal AMPK
Zhang, C., Li, M., Wang, Y., Li, X., Zong, Y., Long, S., Zhang, M., Feng, J.-W., Wei, X., Liu, Y., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00640-7 · Cited by 99 · see citing works
Self-citationLoss of Metabolic Plasticity Underlies Metformin Toxicity in Aged Caenorhabditis Elegans
Espada, L., Dakhovnik, A., Chaudhari, P., Martirosyan, A., Miek, L., Poliezhaieva, T., Schaub, Y., Nair, A., Döring, N., Rahnis, N., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00307-1 · Cited by 100 · see citing works
Zheng, M., Wu, C., Yang, K., Yang, Y., Liu, Y., Gao, S., Wang, Q., Li, C., Chen, L., & Li, H. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105367 · Cited by 100 · see citing works
Metformin as an archetype immuno-metabolic adjuvant for cancer immunotherapy
Verdura, S., Cuyàs, E., Martı́n-Castillo, B., & Menéndez, J. A. (2019) · OncoImmunology · doi:10.1080/2162402x.2019.1633235 · Cited by 99 · see citing works
Lessons Learned from Two Decades of Anticancer Drugs
Liu, Z., Delavan, B., Roberts, R. A., & Tong, W. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.06.005 · Cited by 95 · see citing works
The mitochondrial permeability transition: Nexus of aging, disease and longevity
Rottenberg, H., & Hoek, J. B. (2021) · Cells · doi:10.3390/cells10010079 · Cited by 94 · see citing works
Metformin blocks myeloid-derived suppressor cell accumulation through AMPK-DACH1-CXCL1 axis
Qin, G., Lian, J., Huang, L. J., Zhao, Q., Liu, S., Zhang, Z., Chen, X., Yue, D., Li, L., Li, F., et al. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1442167 · Cited by 94 · see citing works
Olatunde, A., Nigam, M., SINGH, R. K., Panwar, A. S., Lasisi, A., Alhumaydhi, F. A., Kumar, V., Mishra, A. P., & Sharifi‐Rad, J. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02202-5 · Cited by 93 · see citing works
Metformin: An old drug against old age and associated morbidities
Salvatore, T., Pafundi, P. C., Morgillo, F., Liello, R. D., Galiero, R., Nevola, R., Marfella, R., Monaco, L., Rinaldi, L., Adinolfi, L. E., et al. (2020) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2020.108025 · Cited by 87 · see citing works
Zhu, Y., Xia, X., He, Q., Xiao, Q.-A., Wang, D., Huang, M., & Zhang, X. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1202463 · Cited by 92 · see citing works
Drug repurposing for the treatment of glioblastoma multiforme
Abbruzzese, C., Matteoni, S., Signore, M., Cardone, L., Nath, K., Glickson, J. D., & Paggi, M. G. (2017) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-017-0642-x · Cited by 86 · see citing works
Wang, C., Zhang, T., Liao, Q., Dai, M., Guo, J., Yang, X., Tan, W., Lin, D., Wu, C., & Zhao, Y. (2021) · Protein & Cell · doi:10.1007/s13238-020-00760-4 · Cited by 82 · see citing works
Denzel, M. S., Lapierre, L. R., & Mack, H. I. D. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.08.001 · Cited by 81 · see citing works
Metformin: A Potential Candidate for Targeting Aging Mechanisms
Hu, D., Xie, F., Xiao, Y., Chen, L., Zhong, J., Huang, D., Chen, J., Wei, J., Jiang, Y., & Zhong, T. (2021) · Aging and Disease · doi:10.14336/ad.2020.0702 · Cited by 79 · see citing works
Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L antitumoral activities
Pulito, C., Mori, F., Sacconi, A., Goeman, F., Ferraiuolo, M. A., Pasanisi, P., Campagnoli, C., Berrino, F., Fanciulli, M., Ford, R. J., et al. (2017) · Cell Discovery · doi:10.1038/celldisc.2017.22 · Cited by 76 · see citing works
Sorrenti, V., Benedetti, F., Buriani, A., Fortinguerra, S., Caudullo, G., Davinelli, S., Zella, D., & Scapagnini, G. (2022) · Pharmaceuticals · doi:10.3390/ph15080912 · Cited by 78 · see citing works
Inflammatory macrophages reprogram to immunosuppression by reducing mitochondrial translation
Cortés, M., Brischetto, A., Martínez-Campanario, M. C., Ninfali, C., Domínguez, V., Fernández, S., Celis, R., Esteve‐Codina, A., Lozano, J. J., Sidorova, J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42277-4 · Cited by 75 · see citing works
Metformin and Breast Cancer: Molecular Targets
Faria, J., Negalha, G. D. C., Azevedo, A., & Martel, F. (2019) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-019-09429-z · Cited by 75 · see citing works
Metformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway
Xiao, Y., Liu, F., Li, S., Jiang, N., Yu, C., Zhu, X., Qin, Y., Hui, J., Meng, L., Song, C., et al. (2019) · Virulence · doi:10.1080/21505594.2019.1706305 · Cited by 74 · see citing works
Meng, J.-G., & Ferguson, S. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201712177 · Cited by 70 · see citing works
Xia, C., Liu, C., He, Z., Cai, Y., & Chen, J. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01627-6 · Cited by 74 · see citing works
Zhou, P., Li, B., Liu, F.-R., Zhang, M., Wang, Q., Li, Y., Xu, C., Liu, Y., Yao Zong, Y. U. A. N., & Li, D. (2017) · Oncotarget · doi:10.18632/oncotarget.15692 · Cited by 71 · see citing works
Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells
Mishra, A. K., & Dingli, D. (2019) · Leukemia · doi:10.1038/s41375-019-0470-4 · Cited by 71 · see citing works
Association of metformin use and cancer incidence: a systematic review and meta-analysis
O’Connor, L. E., Bailey‐Whyte, M., Bhattacharya, M., Butera, G., Hardell, K. N. L., Seidenberg, A. B., Castle, P. E., & Loomans-Kropp, H. A. (2024) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djae021 · Cited by 71 · see citing works
Calorie Restriction Mimetics: Upstream-Type Compounds for Modulating Glucose Metabolism
Shintani, H., Shintani, T., Ashida, H., & Sato, M. (2018) · Nutrients · doi:10.3390/nu10121821 · Cited by 68 · see citing works
Health benefits of late-onset metformin treatment every other week in mice
Alfaras, I., Mitchell, S. J., Mora, H., Lugo, D. R., Warren, A., Navas-Enamorado, I., Hoffmann, V., Hine, C., Mitchell, J. R., Le Couteur, D. G., et al. (2017) · npj Aging and Mechanisms of Disease · doi:10.1038/s41514-017-0018-7 · Cited by 68 · see citing works
Zhang, R., He, Y., Yao, L., Chen, J., Zhu, S., Rao, X., Tang, P., You, J., Hua, G., Zhang, L., et al. (2021) · Environment International · doi:10.1016/j.envint.2020.106244 · Cited by 65 · see citing works
Self-citationMetformin's Mechanisms in Attenuating Hallmarks of Aging and Age-Related Disease
Cheng, F., Liu, Y.-L., Du, J., & Lin, J. (2022) · Aging and Disease · doi:10.14336/ad.2021.1213 · Cited by 69 · see citing works
Therapeutic Repurposing of Biguanides in Cancer
Zhao, H., Swanson, K. D., & Zheng, B. (2021) · Trends in cancer · doi:10.1016/j.trecan.2021.03.001 · Cited by 65 · see citing works
Self-citationUnderstanding the action mechanisms of metformin in the gastrointestinal tract
Cheng, M., Ren, L., Jia, X., Wang, J., & Cong, B. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1347047 · Cited by 70 · see citing works
Nutritional Regulation of Intestinal Stem Cells
Alonso, S., & Yilmaz, Ö. H. (2018) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-082117-051644 · Cited by 61 · see citing works
PPARγ agonists delay age‐associated metabolic disease and extend longevity
Xu, L., Ma, X., Verma, N., Pèrié, L., Pendse, J., Shamloo, S., Josephson, A. M., Wang, D., Qiu, J., Guo, M., et al. (2020) · Aging Cell · doi:10.1111/acel.13267 · Cited by 63 · see citing works
Metformin ameliorates arsenic trioxide hepatotoxicity via inhibiting mitochondrial complex I
Ling, S., Shan, Q., Liu, P., Feng, T., Zhang, X., Xiang, P., Chen, K., Xie, H., Song, P., Zhou, L., et al. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.482 · Cited by 61 · see citing works
Metabolic Adaptations of CD4+ T Cells in Inflammatory Disease
Dumitru, C., Kabat, A. M., & Maloy, K. J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00540 · Cited by 62 · see citing works
Li, K., Zhang, T., Wang, F., Cui, B., Zhao, C.-X., Yu, J., Lv, X., Zhang, X., Yang, Z.-N., Huang, B., et al. (2018) · Oncogene · doi:10.1038/s41388-018-0172-9 · Cited by 58 · see citing works
Targeting Mitochondria to Counteract Age-Related Cellular Dysfunction
Madreiter‐Sokolowski, C. T., Sokolowski, A., Waldeck‐Weiermair, M., Malli, R., & Graier, W. F. (2018) · Genes · doi:10.3390/genes9030165 · Cited by 60 · see citing works
Changes of Cell Biochemical States Are Revealed in Protein Homomeric Complex Dynamics
Stynen, B., Abd-Rabbo, D., Kowarzyk, J., Miller‐Fleming, L., Aulakh, S. K., Garneau, P., Ralser, M., & Michnick, S. W. (2018) · Cell · doi:10.1016/j.cell.2018.09.050 · Cited by 59 · see citing works
A Systems Approach to Refine Disease Taxonomy by Integrating Phenotypic and Molecular Networks
Zhou, X., Lei, L., Liu, J. H., Halu, A., Zhang, Y., Li, B., Guo, Z., Liu, G., Sun, C., Loscalzo, J., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.04.002 · Cited by 55 · see citing works
Xiao, Y., Liu, F., Kong, Q., Zhu, X., Wang, H., Li, S., Jiang, N., Yu, C., & Liu, Y. (2022) · Aging Cell · doi:10.1111/acel.13567 · Cited by 56 · see citing works
The Use of Metformin to Increase the Human Healthspan
Piskovatska, V., Storey, K. B., Vaiserman, A. M., & Lushchak, O. V. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-42667-5_13 · Cited by 54 · see citing works
Disease or not, aging is easily treatable
Blagosklonny, M. V. (2018) · Aging · doi:10.18632/aging.101647 · Cited by 54 · see citing works
Qin, S., Wang, Y., Li, L., Liu, J., Xiao, C., Duan, D., Hao, W., Qin, C., Chen, J., Yao, L., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111381 · Cited by 53 · see citing works
Self-citationAnti-Aging Effects of Calorie Restriction (CR) and CR Mimetics Based on the Senoinflammation Concept
Kim, D. H., Bang, E., Jung, H. J., Noh, S. G., Yu, B. P., Choi, Y. J., & Chung, H. Y. (2020) · Nutrients · doi:10.3390/nu12020422 · Cited by 53 · see citing works
Regulation of organelle function by metformin
Kim, J., & You, Y. (2017) · IUBMB Life · doi:10.1002/iub.1633 · Cited by 49 · see citing works
Chen, X., Bahramimehr, F., Shahhamzehei, N., Fu, H., Lin, S., Wang, H., Li, C., Efferth, T., & Hong, C. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155665 · Cited by 50 · see citing works
Kosaisawe, N., Sparta, B., Pargett, M., Teragawa, C., & Albeck, J. G. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.01.014 · Cited by 46 · see citing works
Metformin for non-small cell lung cancer patients: Opportunities and pitfalls
Lévy, A., & Doyen, J. (2018) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2018.03.001 · Cited by 46 · see citing works
Low-density-lipoprotein-receptor-related protein 1 mediates Notch pathway activation
Bian, W., Tang, M., Jiang, H., Xu, W., Hao, W., Sui, Y., Hou, Y., Nie, L., Zhang, H., Wang, C., et al. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.09.015 · Cited by 44 · see citing works
Self-citationMetformin: Restraining Nucleocytoplasmic Shuttling to Fight Cancer and Aging
Castillo-Quan, J. I., & Blackwell, T. K. (2016) · Cell · doi:10.1016/j.cell.2016.11.058 · Cited by 44 · see citing works
Onken, B., Sedore, C. A., Coleman-Hulbert, A. L., Hall, D., Johnson, E., Jones, E. G., Banse, S. A., Huynh, P., Guo, S., Xue, J., et al. (2021) · Aging Cell · doi:10.1111/acel.13488 · Cited by 43 · see citing works
Repurposing of Chronically Used Drugs in Cancer Therapy: A Chance to Grasp
Hijazi, M. A., Gessner, A., & El‐Najjar, N. (2023) · Cancers · doi:10.3390/cancers15123199 · Cited by 42 · see citing works
Cedillo, L., Li, S., Ahsan, F. M., Stuhr, N. L., Zhou, Y., Zhang, Y., Adedoja, A., Murphy, L., Yerevanian, A. I., Emans, S. W., et al. (2023) · eLife · doi:10.7554/elife.82210 · Cited by 41 · see citing works
Self-citationNuclear Functions of TOR: Impact on Transcription and the Epigenome
Laribee, R. N., & Weisman, R. (2020) · Genes · doi:10.3390/genes11060641 · Cited by 43 · see citing works
Effects of High Dietary Carbohydrate and Lipid Intake on the Lifespan of C. elegans
Franco-Juárez, B., Gómez‐Manzo, S., Hernández‐Ochoa, B., Cárdenas‐Rodríguez, N., Arreguín‐Espinosa, R., de la Cruz, V. P., & Ortega-Cuéllar, D. (2021) · Cells · doi:10.3390/cells10092359 · Cited by 38 · see citing works
Shim, S. M., Choi, H. R., Kwon, S. C., Kim, H. Y., Sung, K. W., Jung, E. J., Mun, S. R., Bae, T. H., Kim, D. H., Son, Y. S., et al. (2022) · Autophagy · doi:10.1080/15548627.2022.2126617 · Cited by 39 · see citing works
Qian, R., Lv, J. C., & Long, Y. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.8b04159 · Cited by 38 · see citing works
Effects of Lycium barbarum Polysaccharides on Health and Aging of C. elegans Depend on daf-12/daf-16
Zhang, Z., Zhou, Y., Fan, H., Kirunda, J. B., Zhao, Y., Zhan, X., Yang, L., & Jia, Y. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/6379493 · Cited by 36 · see citing works
Mbara, K., Mato, P. E. M., Driver, C., Nzuza, S., Mkhombo, N. T., Gcwensa, S. K., Mcobothi, E. N., & Owira, P. M. O. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.173934 · Cited by 21 · see citing works
Yeo, S. K., Paul, R., Haas, M., Wang, C., & Guan, J. (2018) · Autophagy · doi:10.1080/15548627.2018.1460010 · Cited by 35 · see citing works
Song, J., Jiang, G., Zhang, J., Guo, J., Li, Z., Hao, K., Liu, L., Cheng, Z., Tong, X., & Dai, F. (2019) · Aging · doi:10.18632/aging.101746 · Cited by 36 · see citing works
The direct targets of metformin in diabetes and beyond
Yao, L., Wang, L., Zhang, R., Soukas, A. A., & Wu, L. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.07.017 · Cited by 39 · see citing works
Self-citationXia, C., Fang, Y., He, Z., & Cai, Y. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109762 · Cited by 32 · see citing works
Genes in human obesity loci are causal obesity genes in C. elegans
Ke, W., Reed, J. N., Yang, C., Higgason, N. M., Rayyan, L., Wählby, C., Carpenter, A. E., Civelek, M., & O’Rourke, E. J. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009736 · Cited by 32 · see citing works
Vicentini, M., Ballotari, P., Rossi, P. G., Venturelli, F., Sacchettini, C., Greci, M., Mangone, L., Pezzarossi, A., & Manicardi, V. (2018) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2018.04.036 · Cited by 30 · see citing works
Ryan, K. C., Ashkavand, Z., Sarasija, S., Laboy, J. T., Samarakoon, R., & Norman, K. R. (2021) · Aging Cell · doi:10.1111/acel.13472 · Cited by 9 · see citing works
Gorgich, E. A. C., Parsaie, H., Yarmand, S., Baharvand, F., & Sarbishegi, M. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113343 · Cited by 28 · see citing works
Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits
Yip, J., Chiang, G. S. H., Lee, I. C. J., Lehming-Teo, R., Dai, K., Dongol, L., Wang, L. Y.-T., Teo, D. W. X., Seah, G. T., & Lehming, N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26010364 · Cited by 28 · see citing works
- Authors
- Wu, L., Zhou, B., Oshiro-Rapley, N., Li, M., Paulo, J. A., Webster, C. M., Mou, F., Kacergis, M. C., Talkowski, M. E., Carr, C. E., Gygi, S. P., Zheng, B., & Soukas, A. A.
- Affiliations
- Broad Institute (US)
- Massachusetts General Hospital (US)
- Harvard University (US)
- Corresponding author
- Soukas, Alexander A.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 167
- Issue
- 7
- Pages
- 1705-1718.e13
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5390486
- OpenAlex
- W2564326418
- Cited by
- 227
- References
- 48
- Citations by year
- 2026: 13 · 2025: 18 · 2024: 26 · 2023: 17 · 2022: 19 · 2021: 22 · 2020: 26 · 2019: 24 · 2018: 35 · 2017: 26 · 2016: 1
- FWCI
- 14.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (P40 OD010440, R03DK098436, K08DK087941, R01DK072041, R01CA166717)
- Broad Institute SPARC Grant
- NORC of Harvard (P30DK040561)
- Boston Area DERC (P30DK057521)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- metformin, biguanides, growth inhibition, nuclear pore complex, acyl-CoA dehydrogenase, mTORC1, mitochondrial respiration, nuclear exclusion, melanoma, pancreatic cancer, lifespan extension, cancer therapy, Caenorhabditis elegans
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Aging, Animals, DNA-Binding Proteins, Humans, Longevity, Metformin, Mitochondria, Neoplasms, Oxidative Phosphorylation, Transcription Factors, Signal Transduction, Caenorhabditis elegans, Monomeric GTP-Binding Proteins, Nuclear Pore, Caenorhabditis elegans Proteins, Acyl-CoA Dehydrogenase, Cell Line, Tumor, Multiprotein Complexes, Body Size, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
