Metformin as a tool to target aging

Barzilai, Nir; Crandall, Jill P.; Kritchevsky, Stephen B.; Espeland, Mark A.

doi:10.1016/j.cmet.2016.05.011

Cited by 1,096Metabolism, Diabetes, and CancerGenetics, Aging, and Longevity in Model OrganismsDiabetes Treatment and Management

Metformin as a tool to target aging

Open access

Barzilai, Nir, Crandall, Jill P., Kritchevsky, Stephen B., Espeland, Mark A.·2016·Cell Metabolism

DOI 10.1016/j.cmet.2016.05.011PMC PMC5943638

Open this paper in CoChat — free account Open PDF

Abstract

Aging has been targeted by genetic and dietary manipulation and by drugs in order to increase lifespan and health span in numerous models. Metformin, which has demonstrated protective effects against several age-related diseases in humans, will be tested in the TAME (Targeting Aging with Metformin) trial, as the initial step in the development of increasingly effective next-generation drugs.

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

Crossref · 10.1016/j.cmet.2016.05.011

Cites

82 of 82 references verified0 citation errors · 0 not checkable

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?

Metformin reduces age-related disorders and improves healthspan.
“Metformin- a biguanide that combats age-related disorders and improves healthspan”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Barzilai et al. 2016
Association studies suggest metformin decreases the incidence of most age-related cancers and Alzheimer's disease, and clinical studies support reduced cognitive decline and mortality in diabetics taking metformin compared with non-diabetics.
“Association studies suggest a decrease in the incidence of most age-related cancers, Alzheimer’s Disease while clinical studies support metformin’s role in a decrease in cognitive decline and reduced mortality in diabetics taking metformin compared to non-diabetics”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Barzilai et al. 2016
A main action of metformin is inhibition of mitochondrial complex I, leading to downstream effects on metabolic and non-metabolic pathways involved in aging.
“One of the main actions of metformin is the inhibition of mitochondrial complex I (NADH:ubiquinone oxidoreductase), that leads to multiple downstream effects both on metabolic and non-metabolic pathways responsible in the aging process”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Barzilai et al. 2016
In humans, metformin has been used clinically for over 60 years, is extensively studied, has a high safety profile, and is positioned to affect pathways of aging and age-related diseases.
“In humans, metformin has been in clinical use for over 60 years, studied extensively, has a high safety profile and is uniquely positioned to intervene several crucial pathways responsible for aging and age-related diseases”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Barzilai et al. 2016
Metformin has been shown to alleviate aging in preclinical studies.
“Metformin, a widely prescribed antidiabetic drug, has been shown to alleviate aging in preclinical studies [177].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [177]

Metformin is an activator of 5′ AMP-activated protein kinase (AMPK).
“New insights may also come from the use of caloric restriction mimetics, such as metformin, an activator of 5′ AMP-activated protein kinase (AMPK).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [94]
The lifespan and healthspan of invertebrates are extended by mutations in pathways such as DAF-2, a gene that encodes for the IGF-1 pathway in C. elegans, or the mTOR signaling pathways that are linked to accelerating the aging process.
“The lifespan and healthspan of invertebrates are extended by mutations in pathways such as the DAF-2, a gene that encodes for the IGF-1 pathway in the nematode Caenorhabditis elegans (C. elegans), or the mTOR signaling pathways that are linked to accelerating the aging process (60, 62–65).”
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 [60]
The same pathways studied in C. elegans have also been investigated in mammals, where lifespan and healthspan were prolonged through modifying the aging pathways or through drugs, including metformin.
“The same pathways studied in C. elegans have also been investigated in mammals, where lifespan and healthspan were prolonged through modifying the ‘aging’ pathways or through drugs, including metformin (60, 87).”
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 [60]
The TAME trial is a double-blinded, placebo-controlled, multicenter trial planned to involve 14 research centers in the USA and enroll 3000 ethnically diverse, non-diabetic subjects aged 65-80.
“Targeting Aging with Metformin (TAME) trial is a double-blinded, placebo-controlled, multicenter trial that is planned to involve 14 research centers in the USA, and subject to funding and approval, will enroll 3000 ethnically diverse, non-diabetic subjects aged 65–80 (60, 261).”
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 [60]
It is argued that TAME trial outcomes will give more insight on whether metformin decreases the risk of developing age-dependent diseases, excluding diabetes, in non-diabetic individuals, and potentially provide a tool to target aging itself.
“It is argued that TAME trial outcomes will give more insight on whether metformin decreases the risk of developing age-dependent diseases, excluding diabetes, in non-diabetic individuals, and potentially provide a tool to target aging itself and not related diseases individually (60, 261).”
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 [60]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011 · see citing works
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)
(1998) · The Lancet · doi:10.1016/s0140-6736(98)07037-8 · Cited by 8,247 · see citing works
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group.
(1998) · PubMed · Cited by 4,290 · 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
Extending Healthy Life Span—From Yeast to Humans
Fontana, L., Partridge, L., & Longo, V. D. (2010) · Science · doi:10.1126/science.1172539 · Cited by 3,023 · 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
Metformin: An Old Drug for the Treatment of Diabetes But a New Drug for the Protection of the Endothelium
Kinaan, M., Ding, H., & Triggle, C. R. (2015) · Medical Principles and Practice · doi:10.1159/000381643 · Cited by 1,515 · see citing works
Metformin: from mechanisms of action to therapies
Foretz, M., Guigas, B., Bertrand, L., Pollak, M., & Viollet, B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.09.018 · Cited by 1,501 · see citing works
Metformin improves healthspan and lifespan in mice
Martin-Montalvo, A., Mercken, E. M., Mitchell, S. J., Palacios, H. H., Mote, P. L., Scheibye-Knudsen, M., Gomes, A. P., Ward, T. M., Minor, R. K., Blouin, M.-J., et al. (2013) · Nature Communications · doi:10.1038/ncomms3192 · Cited by 1,445 · see citing works
Promoting Health and Longevity through Diet: From Model Organisms to Humans
Fontana, L., & Partridge, L. (2015) · Cell · doi:10.1016/j.cell.2015.02.020 · Cited by 1,245 · see citing works
Metformin Inhibits Hepatic Gluconeogenesis in Mice Independently of the LKB1/AMPK Pathway via a Decrease in Hepatic Energy State
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
New Users of Metformin Are at Low Risk of Incident Cancer
Libby, G., Donnelly, L. A., Donnan, P. T., Alessi, D. R., Morris, A. D., & Evans, J. M. M. (2009) · Diabetes Care · doi:10.2337/dc08-2175 · Cited by 996 · 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
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
The Critical Role of Metabolic Pathways in Aging
Barzilai, N., Huffman, D. M., Muzumdar, R. H., & Bartke, A. (2012) · Diabetes · doi:10.2337/db11-1300 · Cited by 803 · see citing works
Self-citation
Rapamycin slows aging in mice
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
Metformin Induces a Dietary Restriction-Like State and the Oxidative Stress Response to Extend C. elegans Healthspan via AMPK, LKB1 and SKN-1
Onken, B., & Driscoll, M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008758 · Cited by 671 · see citing works
Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria
Bridges, H. R., Jones, A. J. Y., Pollak, M. N., & Hirst, J. (2014) · Biochemical Journal · doi:10.1042/bj20140620 · Cited by 661 · see citing works
Metformin inhibits the senescence‐associated secretory phenotype by interfering with <scp>IKK</scp>/<scp>NF</scp>‐κ<scp>B</scp> activation
Moiseeva, O., Deschênes‐Simard, X., St‐Germain, E., Igelmann, S., Huot, G., Cadar, A. E., Bourdeau, V., Pollak, M. N., & Ferbeyre, G. (2013) · Aging Cell · doi:10.1111/acel.12075 · Cited by 654 · 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
Self-citation
Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study
Aroda, V. R., Edelstein, S. L., Goldberg, R. B., Knowler, W. C., Marcovina, S. M., Orchard, T. J., Bray, G. A., Schade, D. S., Temprosa, M. G., White, N. H., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3754 · Cited by 536 · see citing works
Self-citation
Metformin Associated With Lower Cancer Mortality in Type 2 Diabetes
Landman, G. W. D., Kleefstra, N., van Hateren, K. J. J., Groenier, K. H., Gans, R. O. B., & Bilo, H. J. G. (2010) · Diabetes Care · doi:10.2337/dc09-1380 · Cited by 502 · see citing works
Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study
The Diabetes Prevention Program Research Group (2012) · Diabetes Care · doi:10.2337/dc11-1299 · Cited by 494 · see citing works
Improvement of Cardiac Functions by Chronic Metformin Treatment Is Associated With Enhanced Cardiac Autophagy in Diabetic OVE26 Mice
Xie, Z., Lau, K., Eby, B., Lozano, P., He, C., Pennington, B., Li, H., Rathi, S., Dong, Y., Tian, R., et al. (2011) · Diabetes · doi:10.2337/db10-0351 · Cited by 490 · see citing works
Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals
Lee, M.-S., Hsu, C.-C., Wahlqvist, M. L., Tsai, H.-N., Chang, Y., & Huang, Y.-C. (2011) · BMC Cancer · doi:10.1186/1471-2407-11-20 · Cited by 460 · see citing works
Metformin and Cancer Risk and Mortality: A Systematic Review and Meta-analysis Taking into Account Biases and Confounders
Gandini, S., Puntoni, M., Heckman-Stoddard, B. M., Dunn, B. K., Ford, L., DeCensi, A., & Szabo, E. (2014) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-13-0424 · Cited by 457 · see citing works
Metformin and inflammation: its potential Beyond glucose-lowering effect
Saisho, Y. (2015) · Endocrine, Metabolic & Immune Disorders-Drug Targets · doi:10.2174/1871530315666150316124019 · Cited by 450 · see citing works
Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males
Harrison, D. E., Strong, R., Allison, D. B., Ames, B. N., Astle, C. M., Atamna, H., Fernandez, E., Flurkey, K., Javors, M. A., Nadon, N. L., et al. (2014) · Aging Cell · doi:10.1111/acel.12170 · Cited by 445 · see citing works
Long-term Effects of Metformin on Metabolism and Microvascular and Macrovascular Disease in Patients With Type 2 Diabetes Mellitus
Kooy, A., de Jager, J., Lehert, P., Bets, D., Wulffelé, M. G., Donker, A. J. M., & Stehouwer, C. D. A. (2009) · Archives of Internal Medicine · doi:10.1001/archinternmed.2009.20 · Cited by 440 · see citing works
Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling
Kickstein, E., Krauß, S., Thornhill, P., Rutschow, D., Zeller, R., Sharkey, J., Williamson, R., Fuchs, M., Köhler, A., Glossmann, H. H., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912793107 · Cited by 432 · see citing works
Extending the Lifespan of Long-Lived Mice
Bartke, A., Wright, J. C., Mattison, J. A., Ingram, D. K., Miller, R. A., & Roth, G. S. (2001) · Nature · doi:10.1038/35106646 · Cited by 422 · see citing works
Increased Risk of Cognitive Impairment in Patients With Diabetes Is Associated With Metformin
Moore, E. M., Mander, A. G., Ames, D. J., Kotowicz, M. A., Carne, R. P., Brodaty, H., Woodward, M., Boundy, K. L., Ellis, K. A., Bush, A. I., et al. (2013) · Diabetes Care · doi:10.2337/dc13-0229 · Cited by 405 · see citing works
Metformin Activates a Duodenal Ampk-Dependent Pathway to Lower Hepatic Glucose Production in Rats
Duca, F. A., Côté, C. D., Rasmussen, B. A., Zadeh-Tahmasebi, M., Rutter, G. A., Filippi, B. M., & Lam, T. K. T. (2015) · Nature Medicine · doi:10.1038/nm.3787 · Cited by 402 · see citing works
Metformin in patients with advanced pancreatic cancer: a double-blind, randomised, placebo-controlled phase 2 trial
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 reduces endogenous reactive oxygen species and associated DNA damage
Algire, C., Moiseeva, O., Deschênes-Simard, X., Amrein, L., Petruccelli, L., Birman, E., Viollet, B., Ferbeyre, G., & Pollak, M. N. (2012) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-11-0536 · Cited by 372 · see citing works
Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls
Bannister, C. A., Holden, S. E., Jenkins‐Jones, S., Morgan, C. L., Halcox, J. P., Schernthaner, G., Mukherjee, J., & Currie, C. J. (2014) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12354 · Cited by 356 · 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
Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice
Strong, R., Miller, R. A., Astle, C. M., Floyd, R. A., Flurkey, K., Hensley, K. L., Javors, M. A., Leeuwenburgh, C., Nelson, J. F., Ongini, E., et al. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00414.x · Cited by 349 · see citing works
Metformin slows down aging and extends life span of female SHR mice
Anisimov, V. N., Berstein, L. M., Egormin, P. A., Piskunova, T. S., Popovich, I. G., Zabezhinski, M. A., Tyndyk, M. L., Yurova, M. V., Kovalenko, I. G., Poroshina, T. E., et al. (2008) · Cell Cycle · doi:10.4161/cc.7.17.6625 · Cited by 348 · 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
Long-Term Metformin Usage and Cognitive Function among Older Adults with Diabetes
Ng, T. P., Feng, L., Yap, K. B., Lee, T. S., Tan, C. H., & Winblad, B. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-131901 · Cited by 334 · see citing works
Intensive Lifestyle Intervention or Metformin on Inflammation and Coagulation in Participants With Impaired Glucose Tolerance
The Diabetes Prevention Program Research Group (2005) · Diabetes · doi:10.2337/diabetes.54.5.1566 · Cited by 333 · see citing works
Metformin Alleviates Hepatosteatosis by Restoring SIRT1-Mediated Autophagy Induction via an AMP-Activated Protein Kinase-Independent Pathway
Song, Y. M., Lee, Y.-H., Kim, J.-W., Ham, D.-S., Kang, E.-S., Cha, B. S., Lee, H. C., & Lee, B.-W. (2015) · Autophagy · doi:10.4161/15548627.2014.984271 · Cited by 332 · see citing works
The ROS Production Induced by a Reverse-Electron Flux at Respiratory-Chain Complex 1 is Hampered by Metformin
Batandier, C., Guigas, B., Détaille, D., El-Mir, M. Y. A., Fontaine, E. M., Rigoulet, M., & Leverve, X. M. (2006) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-006-9003-8 · Cited by 306 · see citing works
If Started Early in Life, Metformin Treatment Increases Life Span and Postpones Tumors in Female SHR Mice
Anisimov, V. N., Berstein, L. M., Popovich, I. G., Zabezhinski, M. A., Egormin, P. A., Piskunova, T. S., Semenchenko, A. V., Tyndyk, M. L., Yurova, M. N., Kovalenko, I. G., et al. (2011) · Aging · doi:10.18632/aging.100273 · Cited by 285 · see citing works
Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial
Luchsinger, J. A., Perez, T., Chang, H., Mehta, P., Steffener, J., Pradabhan, G., Ichise, M., Manly, J., Devanand, D. P., & Bagiella, E. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-150493 · Cited by 285 · cited 1× · see citing works
“In an unpublished trial, non-diabetic subjects (n = 80) with mild cognitive impairment showed significant improvements in some cognitive domains after 12 months of metformin treatment (Luchsinger et al., 2016).”
Sirtuin 1-Mediated Cellular Metabolic Memory of High Glucose via the LKB1/AMPK/ROS Pathway and Therapeutic Effects of Metformin
Zheng, Z., Chen, H., Li, J., Li, T., Zheng, B., Zheng, Y., Jin, H., He, Y., Gu, Q., & Xu, X. (2012) · Diabetes · doi:10.2337/db11-0416 · Cited by 282 · see citing works
Metformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitus
Guo, M., Mi, J., Jiang, Q., Xu, J., Tang, Y., Tian, G., & Wang, B. (2014) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12265 · Cited by 225 · see citing works
The key role of growth hormone–insulin–IGF-1 signaling in aging and cancer
Anisimov, V. N., & Bartke, A. (2013) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2013.01.005 · Cited by 222 · see citing works
Metformin therapy in a transgenic mouse model of Huntington's disease
Ma, T. C., Buescher, J. L., Oatis, B., Funk, J. A., Nash, A. J., Carrier, R. L., & Hoyt, K. R. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.10.039 · Cited by 220 · see citing works
An aging Interventions Testing Program: study design and interim report
Miller, R. A., Harrison, D. E., Astle, C. M., Floyd, R. A., Flurkey, K., Hensley, K., Javors, M. A., Leeuwenburgh, C., Nelson, J. F., Ongini, E., et al. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00311.x · Cited by 217 · see citing works
Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial
Preiss, D., Lloyd, S. M., Ford, I., McMurray, J. J. V., Holman, R. R., Welsh, P. I., Fisher, M., Packard, C. J., & Sattar, N. A. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70152-9 · Cited by 203 · see citing works
Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila
Slack, C., Foley, A., & Partridge, L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047699 · Cited by 199 · see citing works
Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials
Stevens, R., Ali, R., Bankhead, C. R., Bethel, M. A., Cairns, B. J., Camisasca, R., Crowe, F. L., Farmer, A. A., Harrison, S., Hirst, J. A., et al. (2012) · Diabetologia · doi:10.1007/s00125-012-2653-7 · Cited by 183 · see citing works
Effect of Metformin on Left Ventricular Function After Acute Myocardial Infarction in Patients Without Diabetes
Lexis, C. P. H., van der Horst, I. C. C., Lipšic, E., Wieringa, W. G., de Boer, R. A., van den Heuvel, A. F. M., van der Werf, H. W., Schurer, R. A. J., Pundziūtė, G., Tan, E. S., et al. (2014) · JAMA · doi:10.1001/jama.2014.3315 · Cited by 178 · see citing works
Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo
Anisimov, V. N., Egormin, P. A., Piskunova, T. S., Popovich, I. G., Тындык, М. Л., Yurova, M. N., Zabezhinski, M. A., Anikin, I. V., Karkach, A. S., & Romanyukha, A. A. (2010) · Cell Cycle · doi:10.4161/cc.9.1.10407 · Cited by 172 · see citing works
Type 2 Diabetes and Antidiabetic Medications in Relation to Dementia Diagnosis
Cheng, C., Lin, C.-H., Tsai, Y.-W., Tsai, C.-J., Chou, P.-H., & Lan, T.-H. (2014) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glu073 · Cited by 167 · see citing works
Design of aging intervention studies: the NIA interventions testing program
Nadon, N. L., Strong, R., Miller, R. A., Nelson, J. F., Javors, M. A., Sharp, Z. D., Peralba, J. M., & Harrison, D. E. (2008) · AGE · doi:10.1007/s11357-008-9048-1 · Cited by 156 · see citing works
Metformin Supplementation and Life Span in Fischer-344 Rats
Smith, D. L., Elam, C. F., Mattison, J. A., Lane, M. A., Roth, G. S., Ingram, D. K., & Allison, D. B. (2010) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glq033 · Cited by 153 · see citing works
Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk
Lien, F., Berthier, A., Bouchaert, E., Gheeraert, C., Alexandre, J., Porez, G., Prawitt, J., Dehondt, H., Ploton, M., Colin, S., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci68815 · Cited by 151 · see citing works
Metformin lowers Ser-129 phosphorylated α-synuclein levels via mTOR-dependent protein phosphatase 2A activation
Pérez‐Revuelta, B. I., Hettich, M. M., Ciociaro, A., Rotermund, C., Kahle, P. J., Krauß, S., & Monte, D. A. D. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.175 · Cited by 147 · see citing works
Potent anti-proliferative effects of metformin on trastuzumab-resistant breast cancer cells via inhibition of erbB2/IGF-1 receptor interactions
Liu, B., Fan, Z., Edgerton, S. M., Yang, X., Lind, S. E., & Thor, A. D. (2011) · Cell Cycle · doi:10.4161/cc.10.17.16359 · Cited by 146 · see citing works
HbA1c as a predictor of diabetes and as an outcome in the diabetes prevention program: a randomized clinical trial
Diabetes Prevention Program Research Group (2015) · Diabetes Care · doi:10.2337/dc14-0886 · Cited by 139 · see citing works
Effect of Long-Term Metformin and Lifestyle in the Diabetes Prevention Program and Its Outcome Study on Coronary Artery Calcium
Goldberg, R. B., Aroda, V. R., Bluemke, D. A., Barrett-Connor, E. L., Budoff, M. J., Crandall, J. P., Dabelea, D., Horton, E. S., Mather, K. J., Orchard, T. J., et al. (2017) · Circulation · doi:10.1161/circulationaha.116.025483 · Cited by 138 · see citing works
Self-citation
Diabetes, metformin use, and colon cancer: a population-based cohort study in Taiwan
Tseng, C. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0369 · Cited by 132 · see citing works
Mechanism of Metformin-dependent Inhibition of Mammalian Target of Rapamycin (mTOR) and Ras Activity in Pancreatic Cancer
Nair, V., Sreevalsan, S., Basha, R., Abdelrahim, M., Abudayyeh, A., Rodrigues Hoffman, A., & Safe, S. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.592576 · Cited by 129 · see citing works
Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells
Karnevi, E., Hilmersson, K. S., Andersson, R. E., & Rosendahl, A. H. (2013) · BMC Cancer · doi:10.1186/1471-2407-13-235 · Cited by 128 · see citing works
Activation of AMPK by metformin inhibits TGF-β-induced collagen production in mouse renal fibroblasts
Lu, J., Shi, J., Li, M., Gui, B., Fu, R., Yao, G., Duan, Z., Lv, Z., Yang, Y., Chen, Z., et al. (2015) · Life Sciences · doi:10.1016/j.lfs.2015.01.042 · Cited by 119 · see citing works
Metformin and Cancer Occurrence in Insulin-Treated Type 2 Diabetic Patients
Monami, M., Colombi, C., Balzi, D., Dicembrini, I., Giannini, S., Melani, C., Vitale, V., Romano, D., Barchielli, A., Marchionni, N., et al. (2010) · Diabetes Care · doi:10.2337/dc10-1287 · Cited by 109 · see citing works
Chronic Metformin Associated Cardioprotection Against Infarction: Not Just a Glucose Lowering Phenomenon
Whittington, H. J., Hall, A. R., McLaughlin, C., Hausenloy, D. J., Yellon, D. M., & Mocanu, M. M. (2012) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-012-6425-x · Cited by 106 · see citing works
Antidiabetic drugs and their potential role in treating mild cognitive impairment and Alzheimer's disease.
Alagiakrishnan, K., Sankaralingam, S., Ghosh, M., Mereu, L., & Senior, P. A. (2013) · PubMed · Cited by 98 · see citing works
Antihyperglycemic mechanism of metformin occurs via the AMPK/LXRα/POMC pathway
Cho, K., Chung, J., Cho, S. K., Shin, H., Jang, I., Park, J., Yu, K., & Cho, J. (2015) · Scientific Reports · doi:10.1038/srep08145 · Cited by 93 · see citing works
Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice
Allard, J. S., Perez, E., Fukui, K., Carpenter, P., Ingram, D. K., & de Cabo, R. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.12.012 · Cited by 87 · see citing works
Inhibition of lung tumorigenesis by metformin is associated with decreased plasma IGF-I and diminished receptor tyrosine kinase signaling
Quinn, B. J., Dallos, M., Kitagawa, H., Kunnumakkara, A. B., Memmott, R. M., Hollander, M. C., Gills, J. J., & Dennis, P. A. (2013) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-13-0058-t · Cited by 85 · see citing works
Metformin decreases IGF1-induced cell proliferation and protein synthesis through AMP-activated protein kinase in cultured bovine granulosa cells
Tosca, L., Ramé, C., Chabrolle, C., Tesseraud, S., & Dupont, J. (2009) · Reproduction · doi:10.1530/rep-09-0351 · Cited by 84 · see citing works
Lifestyle and Metformin Treatment Favorably Influence Lipoprotein Subfraction Distribution in the Diabetes Prevention Program
Goldberg, R. B., Temprosa, M. G., Otvos, J. D., Brunzell, J. D., Marcovina, S. M., Mather, K. J., Arakaki, R., Watson, K. E., Horton, E. S., & Barrett-Connor, E. L. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-1452 · Cited by 78 · see citing works
The Cardiovascular Effects of Metformin: Further Reasons to Consider An Old Drug as a Cornerstone in the Therapy of Type 2 Diabetes Mellitus
Anfossi, G., Russo, I., Bonomo, K., & Trovati, M. (2010) · Current Vascular Pharmacology · doi:10.2174/157016110791112359 · Cited by 74 · see citing works
Caveolin‐1 is essential for metformin inhibitory effect on IGF1 action in non‐small‐cell lung cancer cells
Salani, B., Maffioli, S., Hamoudane, M., Parodi, A., Ravera, S., Passalacqua, M., Alama, A., Nhiri, M., Cordera, R., & Maggi, D. C. (2011) · The FASEB Journal · doi:10.1096/fj.11-192088 · Cited by 72 · see citing works
Association between guideline recommended drugs and death in older adults with multiple chronic conditions: population based cohort study
Tinetti, M. E., McAvay, G., Trentalange, M. J., Cohen, A. B., & Allore, H. G. (2015) · BMJ · doi:10.1136/bmj.h4984 · Cited by 71 · see citing works
Metformin limits ceramide-induced senescence in C2C12 myoblasts
Jadhav, K. S., Dungan, C. M., & Williamson, D. L. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.11.002 · Cited by 67 · see citing works
Type 2 diabetes in the elderly: an assessment of metformin (metformin in the elderly).
Lalau, J., Vermersch, A., Hary, L., Andréjak, M., Isnard, F., & Quichaud, J. (1990) · PubMed · Cited by 52 · see citing works
Effect of Metformin on Breast Ductal Carcinoma In Situ Proliferation in a Randomized Presurgical Trial
DeCensi, A., Puntoni, M., Guerrieri‐Gonzaga, A., Cazzaniga, M., Serrano, D., Lazzeroni, M., Vingiani, A., Gentilini, O., Petrera, M., Viale, G., et al. (2015) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-15-0048 · Cited by 31 · see citing works

Flagged first, then by citations

1 of the 83 references couldn’t be matched to a known paper.

Sorted by citations

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty
Ferrucci, L., & Fabbri, E. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0064-2 · Cited by 3,690 · see citing works
Facing up to the global challenges of ageing
Partridge, L., Deelen, J., & Slagboom, P. E. (2018) · Nature · doi:10.1038/s41586-018-0457-8 · Cited by 1,475 · see citing works
From discoveries in ageing research to therapeutics for healthy ageing
Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019) · Nature · doi:10.1038/s41586-019-1365-2 · Cited by 1,389 · see citing works
Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States
Mattson, M. P., & Arumugam, T. V. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.05.011 · Cited by 1,242 · see citing works
“cades, inhibits liver glucose production, but also activates multiple cellular pathways that counteract aging processes, including activation of AMPK and inhibition of mTOR and inflammatory pathways (Barzilai et al., 2016).”
Background
Senescent cells: an emerging target for diseases of ageing
Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.116 · Cited by 1,284 · see citing works
Why does COVID-19 disproportionately affect older people?
Mueller, A. L., McNamara, M. S., & Sinclair, D. A. (2020) · Aging · doi:10.18632/aging.103344 · Cited by 1,128 · 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
Metformin: historical overview
Bailey, C. J. (2017) · Diabetologia · doi:10.1007/s00125-017-4318-z · Cited by 1,079 · see citing works
“Advances in pharmacogenomics may better inform responsiveness to metformin and effects on the gut microbiome, and animal studies have intriguingly noted anti-ageing effects of metformin [90, 91].”
Background
Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, M. E., Apte, R. S., Uchida, K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.013 · Cited by 930 · see citing works
“Ce aging healthy and prevent expensive age-associated health problems, efforts to develop effective, affordable, anti-aging interventions have recently been intensified, leading to some promising compounds, such as metformin, rapamycin, and SIRT1 activators (Barzilai et al., 2016; Hubbard and Sinclair, 2014; Lamming e…”
Mechanisms of Vascular Aging
Ungvari, Z., Tarantini, S., Donato, A. J., Galvan, V., & Csiszar, A. (2018) · Circulation Research · doi:10.1161/circresaha.118.311378 · Cited by 919 · see citing works
“There is currently an aging clinical trial, TAME (Targeting Aging With Metformin), that aims to determine whether metformin can delay the onset of age-related diseases in humans.(187) In the context of vascular aging, AMPK was shown to confer vasoprotective effects, augmenting eNOS activation.”
Method
Epigenetic clock analysis of diet, exercise, education, and lifestyle factors
Quach, A., Levine, M. E., Tanaka, T., Lu, A. T., Chen, B. H., Ferrucci, L., Ritz, B., Bandinelli, S., Neuhouser, M. L., Beasley, J. M., et al. (2017) · Aging · doi:10.18632/aging.101168 · Cited by 801 · see citing works
“Metformin, which is a first-line medication for the treatment of type 2 diabetes, has garnered substantial interest by aging researchers [87].”
Mitochondria as a therapeutic target for common pathologies
Murphy, M. P., & Hartley, R. C. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.174 · Cited by 832 · see citing works
Cellular and Molecular Mechanisms of Metformin Action
LaMoia, T. E., & Shulman, G. I. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnaa023 · Cited by 791 · see citing works
“The cancer field has begun to explore the antitumor effect of metformin as a potential treatment for certain cancers (23, 24), and the first trials of metformin for treating aging in healthy humans are currently underway (25, 26).”
Background
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
“Association studies suggest a decrease in the incidence of most age-related cancers, Alzheimer’s Disease while clinical studies support metformin’s role in a decrease in cognitive decline and reduced mortality in diabetics taking metformin compared to non-diabetics (Barzilai et al. 2016).”
BackgroundSelf-citation
A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study
Liu, Z., Kuo, P.-L., Horvath, S., Crimmins, E., Ferrucci, L., & Levine, M. (2018) · PLOS Medicine · doi:10.1371/journal.pmed.1002718 · Cited by 754 · see citing works
Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention
Aiello, A., Farzaneh, F., Candore, G., Caruso, C., Davinelli, S., Gambino, C. M., Ligotti, M. E., Zareian, N., & Accardi, G. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02247 · Cited by 693 · see citing works
“It is a drug, typically administrated in type 2 diabetes but proposed as an antiaging molecule for humans, such as the study called “Targeting Aging with Metformin” (94).”
Background
Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus
Foretz, M., Guigas, B., & Viollet, B. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0242-2 · Cited by 686 · see citing works
A research agenda for ageing in China in the 21st century (2nd edition): Focusing on basic and translational research, long-term care, policy and social networks
Fang, E. F., Xie, C., Schenkel, J. A., Wu, C., Long, Q., Cui, H., Aman, Y., Frank, J., Liao, J., Zou, H., et al. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101174 · Cited by 704 · see citing works
Aging and age‐related diseases: from mechanisms to therapeutic strategies
Li, Z., Zhang, Z., Ren, Y., Wang, Y., Fang, J., Yue, H., Ma, S., & Guan, F. (2021) · Biogerontology · doi:10.1007/s10522-021-09910-5 · Cited by 668 · see citing works
Targeting cellular senescence with senotherapeutics: senolytics and senomorphics
Zhang, L. J., Pitcher, L. E., Prahalad, V., Niedernhofer, L. J., & Robbins, P. D. (2022) · FEBS Journal · doi:10.1111/febs.16350 · Cited by 648 · 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
PGC-1α Is a Master Regulator of Mitochondrial Lifecycle and ROS Stress Response
Abu Shelbayeh, O., Arroum, T., Morris, S., & Busch, K. B. (2023) · Antioxidants · doi:10.3390/antiox12051075 · Cited by 552 · see citing works
Metformin and Its Benefits for Various Diseases
Lv, Z., & Guo, Y. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00191 · Cited by 544 · see citing works
Immunosenescence: a key player in cancer development
Lian, J., Yue, Y., Yu, W., & Zhang, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00986-z · Cited by 510 · see citing works
Reversal of epigenetic aging and immunosenescent trends in humans.
Fahy, G. M., Brooke, R. T., Watson, J. P., Good, Z., Vasanawala, S. S., Maecker, H., Leipold, M. D., Lin, D. T. S., Kobor, M. S., & Horvath, S. (2019) · Aging Cell · doi:10.1111/acel.13028 · Cited by 477 · see citing works
Biological Versus Chronological Aging
Hamczyk, M. R., Nevado, R. M., Barettino, A., Fuster, V., & Andrés, V. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.11.062 · Cited by 503 · see citing works
Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice
Newman, J. C., Covarrubias, A. J., Zhao, M., Yu, X., Gut, P., Ng, C.-P., Huang, Y., Haldar, S., & Verdin, E. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.004 · Cited by 493 · see citing works
“…responsive networks has led to the first drug found to extend lifespan in healthy mammals— rapamycin (Harrison et al., 2009)—and the first candidate intervention for testing healthspan extension in a human clinical trial—metformin (Barzilai et al., 2016; Martin-Montalvo et al., 2013).”
Background
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
Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis
Campbell, J. M., Bellman, S. M., Stephenson, M. D., & Lisy., K. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.08.003 · Cited by 455 · see citing works
mTOR as a central regulator of lifespan and aging
Papadopoli, D. J., Boulay, K., Kazak, L., Pollak, M., Mallette, F. A., Topisirović, I., & Hulea, L. (2019) · F1000Research · doi:10.12688/f1000research.17196.1 · Cited by 431 · see citing works
Autophagy and the cell biology of age-related disease
Leidal, A. M., Levine, B., & Debnath, J. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0235-8 · Cited by 424 · see citing works
The landscape of aging
Cai, Y., Song, W., Li, J., Jing, Y., Liang, C., Zhang, L., Zhang, X., Zhang, W., Liu, B., An, Y., et al. (2022) · Science China Life Sciences · doi:10.1007/s11427-022-2161-3 · Cited by 436 · see citing works
Multimorbidity and functional impairment–bidirectional interplay, synergistic effects and common pathways
Calderón‐Larrañaga, A., Vetrano, D. L., Ferrucci, L., Mercer, S. W., Marengoni, A., Onder, G., Eriksdotter, M., & Fratiglioni, L. (2018) · Journal of Internal Medicine · doi:10.1111/joim.12843 · Cited by 419 · see citing works
Metformin: 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
Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation
Xian, H., Liu, Y., Nilsson, A. R., Gatchalian, R., Crother, T. R., Tourtellotte, W. G., Zhang, Y., Alemán-Muench, G. R., Lewis, G. M., Chen, W., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.05.004 · Cited by 407 · see citing works
“Extendedmetformin usage ameliorates other age-related pathologies and extends lifespan and health span in model organisms (Barzilai et al., 2016), effects that are unrelated to glycemic control (Valencia et al.”
Background
Mitochondrial control of immunity: beyond ATP
Mehta, M., Weinberg, S. E., & Chandel, N. S. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.66 · Cited by 398 · see citing works
Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions
Reiter, R., Tan, D., Rosales-Corral, S., Galano, A., Zhou, X., & Xu, B. (2018) · Molecules · doi:10.3390/molecules23020509 · Cited by 393 · see citing works
“Yet, interest in sole treatments such as metformin [217,218] is in vogue, and this molecule has generated a clinical trial [219].”
Background
Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer
Yang, J., Zhou, Y., Xie, S., Wang, J., Li, Z., Chen, L., Mao, M., Chen, C., Huang, A., Chen, Y., et al. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02012-7 · Cited by 386 · see citing works
A framework for selection of blood-based biomarkers for geroscience-guided clinical trials: report from the TAME Biomarkers Workgroup
Justice, J. N., Ferrucci, L., Newman, A. B., Aroda, V. R., Bahnson, J. L., Divers, J., Espeland, M. A., Marcovina, S., Pollak, M. N., Kritchevsky, S. B., et al. (2018) · GeroScience · doi:10.1007/s11357-018-0042-y · Cited by 359 · see citing works
Self-citation
Epigenetic clock: A promising biomarker and practical tool in aging
Duan, R., Fu, Q., Sun, Y., & Li, Q. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101743 · Cited by 353 · 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
Control of mitochondrial superoxide production by reverse electron transport at complex I
Robb, E. L., Hall, A. R., Prime, T. A., Eaton, S. D., Szibor, M., Viscomi, C. F., James, A. M., & Murphy, M. P. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.003647 · Cited by 322 · see citing works
“production by RET, in addition to stimulating AMP-activated protein kinase by inhibiting complex I (46, 47).”
Background
Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy
Elliott, M. L., Caspi, A., Houts, R., Ambler, A. P., Broadbent, J. M., Hancox, R. J., Harrington, H., Hogan, S., Keenan, R. J., Knodt, A. R., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00044-4 · Cited by 330 · see citing works
The Therapeutic Potential of Metformin in Neurodegenerative Diseases
Rotermund, C., Machetanz, G., & Fitzgerald, J. C. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00400 · Cited by 310 · see citing works
Interconnections between Inflammageing and Immunosenescence during Ageing
Teissier, T., Boulanger, É., & Cox, L. S. (2022) · Cells · doi:10.3390/cells11030359 · Cited by 310 · see citing works
“Epidemiological studies suggest improved health in human subjects taking metformin, even above health baselines of age-matched non-diabetic controls [421], although effects were found to be dose-dependent in ITP trials in mice [422,423].”
Background
Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss
Day, E. A., Ford, R. J., Smith, B. K., Mohammadi-Shemirani, P., Morrow, M. R., Gutgesell, R. M., Lu, R., Raphenya, A. R., Kabiri, M., McArthur, A. G., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0146-4 · Cited by 307 · see citing works
Targeting senescent cells in translational medicine
Pàez‐Ribes, M., González‐Gualda, E., Doherty, G. J., & Muñoz‐Espín, D. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201810234 · Cited by 289 · see citing works
“Treatment of mice with metformin is associated with a reduction in oxidative stress and inflammation, resulting in extension of lifespan and healthspan (Barzilai et al, 2016).”
Background
The economic value of targeting aging
Scott, A. J., Ellison, M., & Sinclair, D. A. (2021) · Nature Aging · doi:10.1038/s43587-021-00080-0 · Cited by 267 · see citing works
Drosophila as a model for ageing
Piper, M. D. W., & Partridge, L. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.09.016 · Cited by 273 · see citing works
Metformin activates AMPK through the lysosomal pathway
Zhang, C.-S., Li, M., Ma, T., Zong, Y., Cui, J., Feng, J.-W., Wu, Y.-Q., Lin, S.-Y., & Lin, S.-C. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.003 · Cited by 280 · see citing works
“Administration of metformin to nematodes (C. elegans) and mice gave rise to extended lifespan and health span (Barzilai et al., 2016).”
Background
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
“gov, NCT02874924); metformin, which activates AMPK and sirtuins (Barzilai et al., 2016) (ClinicalTrials.”
Background
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
Senolytics and senomorphics: Natural and synthetic therapeutics in the treatment of aging and chronic diseases
Lagoumtzi, S. M., & Chondrogianni, N. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.05.003 · Cited by 279 · 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
“It is argued that TAME trial outcomes will give more insight on whether metformin decreases the risk of developing age-dependent diseases, excluding diabetes, in non-diabetic individuals, and potentially provide a tool to target aging itself and not related diseases individually (60, 261).”
BackgroundInfluential
Metformin: Is it a drug for all reasons and diseases?
Triggle, C. R., Mohammed, I., Bshesh, K., Marei, I., Ye, K., Ding, H., MacDonald, R. S., Hollenberg, M. D., & Hill, M. A. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155223 · Cited by 282 · 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
“…currently not possible to measure agmatine production by microbes in either model organisms or humans, future work is need to directly link agmatine production with increased longevity of metformin-treated type 2 diabetic humans compared with matched non-diabetic controls (Barzilai et al., 2016).”
Result
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
“Metformin has been explored as an anti-aging agent in model organisms and humans [16,17], given its excellent safety record for over six decades in the clinic, well-documented beneficial properties in cardioprotection, and potential value in cancer prevention and treatment [18,19].”
Background
Horizons in the evolution of aging
Flatt, T., & Partridge, L. (2018) · BMC Biology · doi:10.1186/s12915-018-0562-z · Cited by 255 · see citing works
Telomere and its role in the aging pathways: telomere shortening, cell senescence and mitochondria dysfunction
Zhu, Y., Liu, X., Ding, X., Wang, F., & Geng, X. (2019) · Biogerontology · doi:10.1007/s10522-018-9769-1 · Cited by 255 · see citing works
Role of AMPK mediated pathways in autophagy and aging
Ge, Y., Zhou, M., Chen, C., Wu, X., & Wang, X. (2021) · Biochimie · doi:10.1016/j.biochi.2021.11.008 · Cited by 253 · see citing works
Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity
Romero, 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
Importance of circadian timing for aging and longevity
Acosta-Rodríguez, V. A., Rijo‐Ferreira, F., Green, C. B., & Takahashi, J. S. (2021) · Nature Communications · doi:10.1038/s41467-021-22922-6 · Cited by 249 · 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
Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults
Konopka, A. R., Laurin, J. L., Schoenberg, H. M., Reid, J. J., Castor, W. M., Wolff, C. A., Musci, R. V., Safairad, O. D., Linden, M. A., Biela, L. M., et al. (2019) · Aging Cell · doi:10.1111/acel.12880 · Cited by 238 · see citing works
Metformin decelerates aging clock in male monkeys
Yang, Y., Lu, X., Liu, N., Ma, S., Zhang, H., Zhang, Z., Yang, K., Jiang, M., Zheng, Z., Qiao, Y., et al. (2024) · Cell · doi:10.1016/j.cell.2024.08.021 · Cited by 227 · see citing works
An Ancient, Unified Mechanism for Metformin Growth Inhibition in C. Elegans and Cancer
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., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.055 · Cited by 227 · see citing works
Neurogenesis in aging and age-related neurodegenerative diseases
Čulig, L., Chu, X., & Bohr, V. A. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101636 · Cited by 229 · see citing works
Key proteins and pathways that regulate lifespan
Pan, H., & Finkel, T. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r116.771915 · Cited by 218 · see citing works
Anti‐aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application
Zhao, P., Sui, B., Liu, N., Lv, Y., Zheng, C., Lu, Y., Huang, W., Zhou, C., Chen, J., Pang, D., et al. (2017) · Aging Cell · doi:10.1111/acel.12635 · Cited by 213 · see citing works
“Furthermore, rejuvenative effects of MET on aged skin were substantial, which may be secondary to angiogenic effects or direct contribution of AMPK pathway that is significant to mediate systemic anti-aging impacts of MET (Barzilai et al., 2016).”
Background
The ageing kidney: Molecular mechanisms and clinical implications
Fang, Y., Gong, A. Y., Haller, S. T., Dworkin, L. D., Liu, Z., & Gong, R. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101151 · Cited by 212 · see citing works
“Hence, it is promising that metformin may be used safely in healthy individuals to prevent ageing and possibly age-related renal changes (Barzilai et al., 2016).”
The Microbiome and Aging
Bana, B., & Cabreiro, F. (2019) · Annual Review of Genetics · doi:10.1146/annurev-genet-112618-043650 · Cited by 207 · 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
“Due to its broad range of health benefits and little side effects, a clinical trial named TAME (Targeting Aging with Metformin) was proposed to evaluate metformin’s protective effects against human aging and age-related diseases (Barzilai et al., 2016).”
Background
Senolytics and senostatics as adjuvant tumour therapy
Short, S. C., Fielder, E., Miwa, S., & von Zglinicki, T. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.01.056 · Cited by 201 · see citing works
“onset of age-related multi-morbidity (the TAME trial, [149]) will provide better evidence as to its potential to treat cancer therapy-related frailty and premature ageing.”
Background
Cellular Senescence and Inflammaging in Age-Related Diseases
Olivieri, F., Prattichizzo, F., Grillari, J., & Balistreri, C. R. (2018) · Mediators of Inflammation · doi:10.1155/2018/9076485 · Cited by 200 · see citing works
“However, at present time, the only scheduled antiaging trial is the Targeting Aging with Metformin (TAME) trial [38].”
Background
Strategies targeting cellular senescence
Ovadya, Y., & Krizhanovsky, V. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95149 · Cited by 200 · see citing works
“Reports of similar effects in human diabetic patients have initiated investigations into metformin’s effects on aging in the general population (89, 90).”
Background
MOTS-c Is an Exercise-Induced Mitochondrial-Encoded Regulator of Age-Dependent Physical Decline and Muscle Homeostasis
Reynolds, J. C., Lai, R. W., Woodhead, J. S. T., Joly, J. H., Mitchell, C. J., Cameron-Smith, D., Lu, R., Cohen, P., Graham, N. A., Benayoun, B. A., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20790-0 · Cited by 199 · see citing works
Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases
Song, P., An, J., & Zou, M.-H. (2020) · Cells · doi:10.3390/cells9030671 · Cited by 198 · see citing works
Mitochondria as an important target of metformin: The mechanism of action, toxic and side effects, and new therapeutic applications
Feng, J., Wang, X., Ye, X., Arés, I., López-Torres, B., Martínez, M., Martínez‐Larrañaga, M., Wang, X., Anadón, A., & Martínez, M. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106114 · Cited by 198 · see citing works
Roles of extracellular vesicles in the aging microenvironment and age‐related diseases
Yin, Y., Chen, H., Wang, Y., Zhang, L., & Wang, X. (2021) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12154 · Cited by 199 · see citing works
Epigenetic effects of metformin: from molecular mechanisms to clinical implications
Bridgeman, S. C., Ellison, G. C., Melton, P. E., Newsholme, P., & Mamotte, C. D. S. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13262 · Cited by 190 · see citing works
“Metformin was also suggested as an antiaging drug as early as the 1970s,(26) and is currently being investigated in randomized controlled trials, for example, the Targeting Aging with Metformin (TAME) trial.(27) Metformin is generally well tolerated, with gastrointestinal disturbances, particularly diarrhoea, being th…”
Background
Metformin and Autoimmunity: A “New Deal” of an Old Drug
Ursini, F., Russo, E., Pellino, G., D’Angelo, S., Chiaravalloti, A., Sarro, G. D., Manfredini, R., & GIORGIO, R. D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01236 · Cited by 195 · see citing works
“These findings, together with ground-breaking studies demonstrating its ability to prolong healthspan and lifespan in mice (4), provided the basis for defining metformin as a potential antiaging molecule (5).”
BackgroundInfluential
Autophagy: A novel mechanism of chemoresistance in cancers
Li, X., Zhou, Y., Li, Y., Yang, L., Ma, Y., Peng, X., Yang, S., Liu, J., & Li, H. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109415 · Cited by 195 · see citing works
An International Perspective on Chronic Multimorbidity: Approaching the Elephant in the Room
Vetrano, D. L., Calderón‐Larrañaga, A., Marengoni, A., Onder, G., Bauer, J. M., Cesari, M., Ferrucci, L., & Fratiglioni, L. (2017) · The Journals of Gerontology Series A · doi:10.1093/gerona/glx178 · Cited by 193 · see citing works
“Interestingly, the Targeting Aging with Metformin (TAME) trial, the first randomized clinical trial testing a drug to slow the aging process, will consider the occurrence of several age-related diseases as the primary endpoint (46).”
Background
Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults
Kulkarni, A. S., Brutsaert, E. F., Anghel, V., Zhang, K., Bloomgarden, N., Pollak, M., Mar, J. C., Hawkins, M., Crandall, J. P., & Barzilai, N. (2018) · Aging Cell · doi:10.1111/acel.12723 · Cited by 183 · see citing works
Self-citation
Should metformin remain the first-line therapy for treatment of type 2 diabetes?
Baker, C. A., Retzik-Stahr, C., Singh, V., Plomondon, R., Anderson, V., & Rasouli, N. (2021) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018820980225 · Cited by 192 · see citing works
Techniques to induce and quantify cellular senescence
Noren Hooten, N., & Evans, M. K. (2017) · Journal of Visualized Experiments · doi:10.3791/55533 · Cited by 178 · see citing works
Metabolic landscape in cardiac aging: insights into molecular biology and therapeutic implications
Xie, S., Xu, S., Deng, W., & Tang, Q. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01378-8 · Cited by 185 · see citing works
Lipids and lipid metabolism in cellular senescence: Emerging targets for age-related diseases
Zeng, Q., Gong, Y., Zhu, N., Shi, Y., Zhang, C., & Li, Q. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102294 · Cited by 188 · see citing works
Anti-senescence compounds: A potential nutraceutical approach to healthy aging
Gurău, F., Baldoni, S., Prattichizzo, F., Espinosa, E., Amenta, F., Procopio, A. D., Albertini, M. C., Bonafè, M., & Olivieri, F. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.05.001 · Cited by 179 · see citing works
Metformin alleviates human cellular aging by upregulating the endoplasmic reticulum glutathione peroxidase 7
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
“The current consensus is that metformin targets multiple cellular signaling pathways closely associated with the development of aging, such as inflammation, cellular survival, stress defense, autophagy, and protein synthesis (Barzilai et al., 2016).”
Background
Metformin attenuated sepsis-related liver injury by modulating gut microbiota
Liang, H., Song, H., Zhang, X., Song, G., Wang, Y., Ding, X., Duan, X., Li, L., Sun, T., & Kan, Q. (2022) · Emerging Microbes & Infections · doi:10.1080/22221751.2022.2045876 · Cited by 175 · see citing works
“17], highlighting its protective role in biologically aged mice and age-related mortality [17].”
Background
Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model
Xu, X., Sun, Y., Cen, X., Shan, B., Zhao, Q., Xie, T., Wang, Z., Hou, T., Xue, Y., Zhang, M., et al. (2021) · Protein & Cell · doi:10.1007/s13238-021-00858-3 · Cited by 171 · see citing works
Association of Neurocognitive and Physical Function With Gait Speed in Midlife
Rasmussen, L. J. H., Caspi, A., Ambler, A. P., Broadbent, J. M., Cohen, H. J., d’Arbeloff, T. C., Elliott, M. L., Hancox, R. J., Harrington, H., Hogan, S., et al. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.13123 · Cited by 172 · see citing works
Cardiac ageing: extrinsic and intrinsic factors in cellular renewal and senescence
Gude, N. A., Broughton, K. M., Firouzi, F., & Sussman, M. A. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0061-5 · Cited by 166 · see citing works
The Business of Anti-Aging Science
de Magalhães, J. P., Stevens, M., & Thornton, D. (2017) · Trends in biotechnology · doi:10.1016/j.tibtech.2017.07.004 · Cited by 167 · see citing works
“One effort, however, is trying to perform the first clinical trial for aging, usingmetformin, which would be an important proof of principle [57].”
Background
Unveiling the Role of Inflammation and Oxidative Stress on Age-Related Cardiovascular Diseases
de Almeida, A. J. P. O., Rezende, M. S. D. A., Dantas, S. H., Silva, S. D. L., de Oliveira, J. C. P. L., de Azevedo, F. D. L. A. A., Alves, R. M. F. R., de Menezes, G. M. S., dos Santos, P. F., Gonçalves, T. A. F., et al. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/1954398 · Cited by 167 · see citing works
“AMPK has been implicated in the control of autophagy, inflammation, mitochondrial dysfunction, and cell survival, being an important target for a healthy aging [251].”
Background
Systematic review and analysis of human proteomics aging studies unveils a novel proteomic aging clock and identifies key processes that change with age
Johnson, A. A., Shokhirev, M. N., Wyss-Coray, T., & Lehallier, B. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101070 · Cited by 166 · see citing works
Metformin regulates mitochondrial biogenesis and senescence through AMPK mediated H3K79 methylation: relevance in age-associated vascular dysfunction
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
Stimulation of AMPK prevents degeneration of photoreceptors and the retinal pigment epithelium
Xu, L., Kong, L., Wang, J., & Ash, J. D. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1802724115 · Cited by 163 · see citing works
“Emerging evidence has shown that metformin also modulates the biology of aging and lifespan (44, 45).”
Background
Senescence and senotherapeutics: a new field in cancer therapy
Myrianthopoulos, V., Evangelou, K., Vasileiou, P. V. S., Cooks, T., Vassilakopoulos, T. P., Pangalis, G. A., Kouloukoussa, M., Kittas, C., Georgakilas, A. G., & Gorgoulis, V. G. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.08.006 · Cited by 160 · see citing works

Authors: Barzilai, N., Crandall, J. P., Kritchevsky, S. B., & Espeland, M. A.
Affiliations: Albert Einstein College of Medicine (US)
Wake Forest University Health Sciences (US)
Corresponding author: Barzilai, Nir
ORCID: Barzilai, Nir
Crandall, Jill P.
Kritchevsky, Stephen B.
Espeland, Mark A.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2016-06
Volume: 23
Issue: 6
Pages: 1060-1065
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2016.05.011
PMC: PMC5943638
OpenAlex: W2422981416
Cited by: 1,096
References: 83
Citations by year: 2026: 129 · 2025: 117 · 2024: 101 · 2023: 108 · 2022: 105 · 2021: 131 · 2020: 127 · 2019: 110 · 2018: 97 · 2017: 59 · 2016: 11 · 2015: 1
FWCI: 8.34
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 378 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (P01AG021654, R24AG044396, P01AG027734, P30AG038072, R37AG018381, R01AG046949, P30AG021332)
National Institute of Diabetes and Digestive and Kidney Diseases (U01DK048349)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: metformin, aging, lifespan extension, healthspan, age-related diseases, anti-aging drugs, drug repurposing
MeSH terms: Aging, Animals, Clinical Trials as Topic, Humans, Longevity, Metformin, Models, Biological, Models, Animal

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

Metformin as a tool to target aging

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks