Development of clinical trials to extend healthy lifespan
Open accessAbstract
Significant progress in defining the biology of aging, particularly in animal models, supports the geroscience hypothesis, which posits that by therapeutically targeting biological aging, the onset of multiple age-related diseases can be delayed ‘en suite’. Geroscience investigators are preparing to test this hypothesis in humans for the first time. In this review, we describe development of large-scale clinical trials designed to determine whether multiple age-related health conditions can be simultaneously alleviated with interventions targeting the underlying biology of aging. We describe the rationale and collaborative, consensus building approach used to design the first aging outcome trial called Targeting Aging with Metformin. Through this case study, we outline features that could be more broadly extended to other geroscience-guided clinical trials, including a process for selecting biochemical and molecular markers of biologic age and we provide a perspective on the potential impact of clinical trials targeting aging.
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Clinical trials using metformin to target ageing have begun.
“Clinical trials utilizing metformin, which activates AMPK, to target ageing have already begun193.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [193]
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 [261]
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 [261]
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Cites
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
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
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
Geroscience: Linking Aging to Chronic Disease
Kennedy, B. K., Berger, S. L., Brunet, A., Campisi, J., Cuervo, A. M., Epel, E. S., Franceschi, C., Lithgow, G. J., Morimoto, R. I., Pessin, J. E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.039 · Cited by 2,764 · see citing works
The Achilles' heel of senescent cells: from transcriptome to senolytic drugs
Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., et al. (2015) · Aging Cell · doi:10.1111/acel.12344 · Cited by 2,562 · see citing works
Self-citationSenolytics improve physical function and increase lifespan in old age
Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., Inman, C. L., Ogrodnik, M. B., Hachfeld, C. M., Fraser, D. G., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0092-9 · Cited by 2,287 · see citing works
Self-citationCaloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys
Colman, R. J., Anderson, R. M., Johnson, S. C., Kastman, E. K., Kosmatka, K. J., Beasley, T. M., Allison, D. B., Cruzen, C., Simmons, H. A., Kemnitz, J. W., et al. (2009) · Science · doi:10.1126/science.1173635 · Cited by 2,277 · see citing works
Kassebaum, N. J., Arora, M., Barber, R. M., Bhutta, Z. A., Brown, J., Carter, A., Casey, D. C., Charlson, F. J., Coates, M. M., Coggeshall, M., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31460-x · Cited by 2,163 · 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
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
Self-citation(2015) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(15)00291-0 · Cited by 1,029 · see citing works
Quantification of biological aging in young adults
Belsky, D. W., Caspi, A., Houts, R., Cohen, H. J., Corcoran, D. L., Danese, A., Harrington, H., Israel, S., Levine, M. E., Schaefer, J. D., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1506264112 · Cited by 1,012 · 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-citationInterventions 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-citationFabbri, E., Zoli, M., González‐Freire, M., Salive, M. E., Studenski, S. A., & Ferrucci, L. (2015) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2015.03.013 · Cited by 560 · see citing works
Molecular and physiological manifestations and measurement of aging in humans
Khan, S. S., Singer, B. D., & Vaughan, D. E. (2017) · Aging Cell · doi:10.1111/acel.12601 · Cited by 530 · see citing works
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
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
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-citationGoldman, D. P., Cutler, D., Rowe, J. W., Michaud, P., Sullivan, J. H., Peneva, D., & Olshansky, S. J. (2013) · Health Affairs · doi:10.1377/hlthaff.2013.0052 · Cited by 312 · see citing works
St Sauver, J. L., Boyd, C. M., Grossardt, B. R., Bobo, W. V., Finney Rutten, L. J., Roger, V. L., Ebbert, J. O., Therneau, T. M., Yawn, B. P., & Rocca, W. A. (2015) · BMJ Open · doi:10.1136/bmjopen-2014-006413 · Cited by 257 · 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
Senotherapeutics for healthy ageing
Niedernhofer, L. J., & Robbins, P. D. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.44 · Cited by 190 · see citing works
Self-citationChange in the Rate of Biological Aging in Response to Caloric Restriction: CALERIE Biobank Analysis
Belsky, D. W., Huffman, K. M., Pieper, C. F., Shalev, I., & Kraus, W. E. (2017) · The Journals of Gerontology Series A · doi:10.1093/gerona/glx096 · Cited by 189 · 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
Strategies and Challenges in Clinical Trials Targeting Human Aging
Newman, J. C., Milman, S., Hashmi, S. K., Austad, S. N., Kirkland, J. L., Halter, J. B., & Barzilai, N. (2016) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw149 · Cited by 137 · see citing works
Self-citationAllard, 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
Clinical Trials Targeting Aging and Age-Related Multimorbidity
Espeland, M. A., Crimmins, E. M., Grossardt, B. R., Crandall, J. P., Gelfond, J., Harris, T. B., Kritchevsky, S. B., Manson, J. E., Robinson, J. G., Rocca, W. A., et al. (2016) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw220 · Cited by 77 · see citing works
Self-citationBiochemical Markers of Aging for Longitudinal Studies in Humans
Engelfriet, P. M., Jansen, E. H. J. M., Picavet, H. S. J., & Dollé, M. E. T. (2013) · Epidemiologic Reviews · doi:10.1093/epirev/mxs011 · Cited by 74 · see citing works
Laksmi, P. W., Setiati, S., Tamin, T. Z., Soewondo, P., Rochmah, W., Nafrialdi, N., & Prihartono, J. (2017) · Acta medica Indonesiana · Cited by 51 · see citing works
Moving Geroscience Into Uncharted Waters: Table 1.
Sierra, F. (2016) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glw087 · Cited by 33 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [2]Services UDoHaH, Prevention CfDCa, Statistics NCfH. Health, United States, 2016: With Chartbook on Long-term Trends in Health. Hyattsville, MD: National Center for Health Statistics, 2017 Contract No.: DHHS Publication No. 2017–1232. 28910066
- [24]Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA. Metformin as a Tool to Target Aging. Cell Metab. 2016; 23(6): 1060– 5. Epub June 14, 2016. doi: 10.1016/j.cmet.2016.05.011. 27304507 PMC5943638 · DOI · Paper page
Cited by
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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
SARS-CoV-2, COVID-19 and the aging immune system
Bartleson, J. M., Radenkovic, D., Covarrubias, A. J., Furman, D., Winer, D. A., & Verdin, E. (2021) · Nature Aging · doi:10.1038/s43587-021-00114-7 · Cited by 359 · see citing works
Autophagy and the hallmarks of aging
Kaushik, S., Tasset, I., Arias, E., Pampliega, O., Wong, E., Martinez-Vicente, M., & Cuervo, A. M. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101468 · Cited by 285 · 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
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
Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms
Chen, S., Gan, D., Lin, S., Zhong, Y., Chen, M., Zou, X., Shao, Z., & Xiao, G. (2022) · Theranostics · doi:10.7150/thno.71360 · Cited by 197 · see citing works
The central moTOR of metabolism
Simcox, J., & Lamming, D. W. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.02.024 · Cited by 162 · see citing works
Kulkarni, A. S., Aleksić, S., Berger, D. M., Sierra, F., Kuchel, G. A., & Barzilai, N. (2022) · Aging Cell · doi:10.1111/acel.13596 · Cited by 129 · see citing works
Self-citationStrategies to Prevent or Remediate Cancer and Treatment-Related Aging
Guida, J., Agurs‐Collins, T., Ahles, T. A., Campisi, J., Dale, W., Demark‐Wahnefried, W., Dietrich, J., Fuldner, R., Gallicchio, L. M., Green, P. A., et al. (2020) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djaa060 · Cited by 108 · see citing works
Self-citationMoving geroscience from the bench to clinical care and health policy
Sierra, F., Caspi, A., Fortinsky, R. H., Haynes, L., Lithgow, G. J., Moffitt, T. E., Olshansky, S. J., Perry, D. P., Verdin, E. M., & Kuchel, G. A. (2021) · Journal of the American Geriatrics Society · doi:10.1111/jgs.17301 · Cited by 94 · see citing works
Self-citationSenescent cells and the incidence of age‐related diseases
Katzir, I., Adler, M., Karin, O., Cohen, N. M., Mayo, A., & Alon, U. (2021) · Aging Cell · doi:10.1111/acel.13314 · Cited by 89 · see citing works
Proteomic aging clock ( PAC ) predicts age‐related outcomes in middle‐aged and older adults
Kuo, C., Chen, Z., Liu, P., Pilling, L. C., Atkins, J. L., Fortinsky, R. H., Kuchel, G. A., & Diniz, B. S. (2024) · Aging Cell · doi:10.1111/acel.14195 · Cited by 73 · see citing works
Self-citationVenn-Watson, S. K., & Schork, N. J. (2023) · Nutrients · doi:10.3390/nu15214607 · Cited by 74 · see citing works
p16 a biomarker of aging and tolerance for cancer therapy
Muss, H. B., Smitherman, A. B., Wood, W. A., Nyrop, K. A., Tuchman, S. A., Randhawa, P. K., Entwistle, A., Mitin, N., & Shachar, S. S. (2020) · Translational Cancer Research · doi:10.21037/tcr.2020.03.39 · Cited by 68 · see citing works
Fülöp, T., Larbi, A., Khalil, A., Cohen, A. A., & Witkowski, J. M. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01508 · Cited by 69 · see citing works
Evaluation of off-label rapamycin use to promote healthspan in 333 adults
Kaeberlein, T. L., Green, A. S., Haddad, G., Hudson, J., Isman, A., Nyquist, A., Rosen, B. S., Suh, Y., Zalzala, S., Zhang, X., et al. (2023) · GeroScience · doi:10.1007/s11357-023-00818-1 · Cited by 67 · see citing works
Genetics of extreme human longevity to guide drug discovery for healthy ageing
Zhang, Z. D., Milman, S., Lin, J.-R., Wierbowski, S. D., Yu, H., Barzilai, N., Gorbunova, V. A., Ladiges, W., Niedernhofer, L. J., Suh, Y., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0247-0 · Cited by 61 · see citing works
Self-citationRoadmap for alleviating the manifestations of ageing in the cardiovascular system
Liberale, L., Tual-Chalot, S., Sedej, S., Ministrini, S., Georgiopoulos, G., Grunewald, M., Bäck, M., Bochaton-Piallat, M.-L., Boon, R. A., Ramos, G. C., et al. (2025) · Nature Reviews Cardiology · doi:10.1038/s41569-025-01130-5 · Cited by 59 · see citing works
Impact of Geroscience on Therapeutic Strategies for Older Adults With Cardiovascular Disease
Forman, D. E., Kuchel, G. A., Newman, J. C., Kirkland, J. L., Volpi, E., Taffet, G. E., Barzilai, N., Pandey, A., Kitzman, D. W., Libby, P., et al. (2023) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2023.05.038 · Cited by 62 · see citing works
Self-citationJustice, J. N., Gubbi, S., Kulkarni, A. S., Bartley, J. M., Kuchel, G. A., & Barzilai, N. (2020) · GeroScience · doi:10.1007/s11357-020-00261-6 · Cited by 53 · see citing works
Self-citationGerobiotics: probiotics targeting fundamental aging processes
Tsai, Y.-C., Cheng, L., Liu, Y.-W., Jeng, O.-J., & Lee, Y. K. (2020) · Bioscience of Microbiota Food and Health · doi:10.12938/bmfh.2020-026 · Cited by 54 · see citing works
Carter, C. S., Richardson, A., Huffman, D. M., & Austad, S. (2020) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glz298 · Cited by 51 · see citing works
Diabetes: Risk factor and translational therapeutic implications for Alzheimer's disease
Cummings, J. L., Ortiz, A. A., Castellino, J., & Kinney, J. W. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15619 · Cited by 50 · see citing works
Osteoarthritis as a systemic disease
Collins, K. H., Haugen, I. K., Neogi, T., & Guilak, F. (2025) · Nature Reviews Rheumatology · doi:10.1038/s41584-025-01332-8 · Cited by 48 · see citing works
Testing the Geroscience Hypothesis: Early Days
Kritchevsky, S. B., & Justice, J. N. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz267 · Cited by 42 · see citing works
Self-citationHernández-Álvarez, D., Mena‐Montes, B., Toledo-Pérez, R., Pedraza-Vázquez, G., López-Cervantes, S. P., Morales-Salazar, A., Hernández-Cruz, E., Lazzarini-Lechuga, R. C., Vázquez-Cárdenas, R. R., Vilchis-DeLaRosa, S., et al. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/3428543 · Cited by 41 · see citing works
Frailty and HIV: Moving from Characterization to Intervention
Erlandson, K. M., & Piggott, D. A. (2021) · Current HIV/AIDS Reports · doi:10.1007/s11904-021-00554-1 · Cited by 41 · see citing works
Cardiovascular aging: from cellular and molecular changes to therapeutic interventions
Vakka, A., Warren, J. S., & Drosatos, K. (2023) · The Journal of Cardiovascular Aging · doi:10.20517/jca.2023.09 · Cited by 42 · see citing works
The role of Caenorhabditis elegans in the discovery of natural products for healthy aging
Kirchweger, B., Zwirchmayr, J., Grienke, U., & Rollinger, J. M. (2023) · Natural Product Reports · doi:10.1039/d3np00021d · Cited by 40 · see citing works
Blümel, J. E., Arteaga, E., Aedo, S., Arriola‐Montenegro, J., López, M., Martino, M., Miranda, C., Miranda, O., Mostajo, D., Ñañez, M., et al. (2020) · Gynecological Endocrinology · doi:10.1080/09513590.2020.1718092 · Cited by 36 · see citing works
Treating age-related multimorbidity: the drug discovery challenge
Ermogenous, C., Green, C., Jackson, T., Ferguson, M. A. J., & Lord, J. M. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.06.016 · Cited by 33 · see citing works
Anti-ageing gene therapy: Not so far away?
Vaiserman, A. M., FALCO, E. D., Koliada, A. K., Maslova, O., & Balistreri, C. R. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100977 · Cited by 30 · see citing works
Repurposing nucleoside reverse transcriptase inhibitors (NRTIs) to slow aging
Brochard, T., McIntyre, R. L., Houtkooper, R. H., Seluanov, A., Gorbunova, V. A., & Janssens, G. E. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102132 · Cited by 26 · see citing works
Defining a longevity biotechnology company
Boekstein, N., Barzilai, N., Bertram, A., Betts-LaCroix, J., Fortney, K., Helliwell, S. B., Hufford, M. R., Mannick, J. B., McLaughlin, J., Mellon, J., et al. (2023) · Nature Biotechnology · doi:10.1038/s41587-023-01854-0 · Cited by 23 · see citing works
Self-citationNo Time to Age: Uncoupling Aging from Chronological Time
Larocca, D., Lee, J., West, M. D., Labat, I., & Sternberg, H. (2021) · Genes · doi:10.3390/genes12050611 · Cited by 22 · see citing works
Does Modulation of an Epigenetic Clock Define a Geroprotector?
Schork, N. J., Beaulieu‐Jones, B. K., Liang, W. S., Smalley, S. L., & Goetz, L. H. (2022) · Advances in Geriatric Medicine and Research · doi:10.20900/agmr20220002 · Cited by 24 · see citing works
Simpson, F. R., Justice, J. N., Pilla, S. J., Kritchevsky, S. B., Boyko, E. J., Munshi, M. N., Ferris, C. K., & Espeland, M. A. (2022) · Diabetes Care · doi:10.2337/dc22-1728 · Cited by 20 · see citing works
Self-citationThe development and benefits of metformin in various diseases
Dong, Y., Qi, Y., Jiang, H., Tian, M., Zhang, Y., Peng, C. S., Li, W.-C., Zhang, Y., Zhou, Y., Zang, Y., et al. (2023) · Frontiers of Medicine · doi:10.1007/s11684-023-0998-6 · Cited by 20 · see citing works
Seo, D. H., Corr, M., Patel, S., Lui, L., Cauley, J. A., Evans, D. S., Mau, T., & Lane, N. E. (2024) · Osteoporosis International · doi:10.1007/s00198-024-07160-y · Cited by 18 · see citing works
Aging as an inflammatory disease and possible reversal strategies
Pawelec, G. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.02.022 · Cited by 18 · see citing works
Cesari, M., Azzolino, D., LeBrasseur, N. K., Whitson, H. E., Rooks, D., Sourdet, S., Angioni, D., Fielding, R. A., Vellas, B. J., Rolland, Y., et al. (2022) · The Journal of Frailty & Aging · doi:10.14283/jfa.2022.62 · Cited by 16 · see citing works
Justice, J. N., Pajewski, N. M., Espeland, M. A., Brubaker, P. H., Houston, D. K., Marcovina, S. M., Nicklas, B. J., Kritchevsky, S. B., & Kitzman, D. W. (2022) · GeroScience · doi:10.1007/s11357-021-00509-9 · Cited by 15 · see citing works
Self-citationDiniz, B. S., Seitz‐Holland, J., Sehgal, R., Kasamoto, J., Higgins‐Chen, A., & Lenze, E. J. (2023) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2023.09.014 · Cited by 15 · see citing works
Hernández-Arciga, U., Hernández-Álvarez, D., López-Cervantes, S. P., López‐Díazguerrero, N. E., Alarcón‐Aguilar, A., Luna‐López, A., & Königsberg, M. (2020) · Biogerontology · doi:10.1007/s10522-020-09894-8 · Cited by 12 · see citing works
Birder, L. A., Wolf‐Johnston, A., Zabbarova, I. V., Ikeda, Y., Robertson, A. M., Cardozo, R., Azari, F., Kanai, A., Kuchel, G. A., & Jackson, E. K. (2023) · The Journals of Gerontology Series A · doi:10.1093/gerona/glad171 · Cited by 12 · see citing works
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Morgado‐Carrasco, D., Gil‐Lianes, J., Jourdain, E., & Piquero‐Casals, J. (2022) · Actas Dermo-Sifiliográficas · doi:10.1016/j.ad.2022.09.021 · Cited by 11 · see citing works
Morgado‐Carrasco, D., Gil‐Lianes, J., Jourdain, E., & Piquero‐Casals, J. (2022) · Actas Dermo-Sifiliográficas · doi:10.1016/j.ad.2022.09.014 · Cited by 11 · see citing works
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Kaeberlein, M. R. (2020) · Translational Medicine of Aging · doi:10.1016/j.tma.2020.01.002 · Cited by 10 · see citing works
Arnason, T., MacDonald‐Dickinson, V., Gaunt, M. C., Davies, G. F., Lobanova, L., Trost, B., Gillespie, Z. E., Waldner, M., Baldwin, P., Borrowman, D., et al. (2022) · Cancers · doi:10.3390/cancers14174215 · Cited by 8 · see citing works
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Zhavoronkov, A. A. (2020) · Science · doi:10.1126/science.aba0833 · Cited by 8 · see citing works
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Johnson, A. A. (2019) · Rejuvenation Research · doi:10.1089/rej.2019.2211 · Cited by 7 · see citing works
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Delrieu, J., & Vellas, B. J. (2020) · Bulletin de l Académie Nationale de Médecine · doi:10.1016/j.banm.2020.01.018 · Cited by 7 · see citing works
Network Topology of Biological Aging and Geroscience-Guided Approaches to COVID-19
LANDAY, A. L., Bartley, J. M., Banerjee, D., Hargis, G. R., Haynes, L., Keshavarzian, A., Kuo, C., Kwon, O. S., Li, S., Li, S., et al. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.695218 · Cited by 6 · see citing works
Self-citationComputAgeBench: Epigenetic Aging Clocks BenchmarkPreprint
Kriukov, D. V., Efimov, E., Kuzmina, E., Dudkovskaia, A., Khrameeva, E. E., & Dylov, D. V. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.06.597715 · Cited by 6 · see citing works
Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming
Zhang, W., Song, S., Zhang, Y., Pan, Y., Hu, D., & Wang, Y. (2026) · npj Aging · doi:10.1038/s41514-026-00355-z · Cited by 6 · see citing works
Rizzo, S. J. S., Finkel, T., Greenspan, S. L., Resnick, N. M., & Brach, J. S. (2023) · Innovation in Aging · doi:10.1093/geroni/igad035 · Cited by 5 · see citing works
RSSDI guidelines for management of type 2 diabetes mellitus in older adults
Jagadeesha, A., Viswanathan, V., Agarwal, S., Maheshwari, A., Virmani, A. K., Nagendra, L., Amarnath, A., Chawla, M. S., Jethwani, P., Parikh, R. M., et al. (2026) · International Journal of Diabetes in Developing Countries · doi:10.1007/s13410-025-01613-8 · Cited by 4 · see citing works
Considerations Regarding Public Use of Longevity Interventions
Liu, Y. J., McIntyre, R. L., & Janssens, G. E. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.903049 · Cited by 3 · see citing works
Stubbs, B. J., Azañedo, G. A., Peralta, S., Diaz, S. R., Gray, W., Alexander, L. E. C., Silverman-Martin, W., Garcia, T. Y., Blonquist, T. M., Upadhyay, V., et al. (2024) · PLoS ONE · doi:10.1371/journal.pone.0307951 · Cited by 3 · see citing works
Commentary: rapamycin for the aging skin
Sell, C. (2020) · GeroScience · doi:10.1007/s11357-020-00184-2 · Cited by 3 · see citing works
Stubbs, B. J., Azañedo, G. A., Peralta, S., Diaz, S. R., Gray, W., Alexander, L. E. C., Silverman-Martin, W., Garcia, T. Y., Blonquist, T. M., Upadhyay, V., et al. (2023) · medRxiv · doi:10.1101/2023.10.25.23297571 · Cited by 3 · see citing works
Minoretti, P., Lista, S., López‐Ortiz, S., Merino-País, M., Santos‐Lozano, A., Lucía, A., & Emanuele, E. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103191 · Cited by 2 · see citing works
Effect of Metformin on Interleukin-6 Expression in Human Fibroblast Cell Aging Model
Achadiyani, A., Prabhasiwi, D., Pratiwi, A. E., Hamudin, A., Heryaman, H., Alfarafisa, N. M., & Atik, N. (2024) · Biomedical & Pharmacology Journal · doi:10.13005/bpj/2977 · Cited by 2 · see citing works
Balancing the promise and risks of gerosciencePreprint
Cohen, A. A., Beard, J., Ferrucci, L., Fülöp, T., Gladyshev, V. N., Moqri, M., Rikkert, M. G. M. O., & Picard, M. A. (2024) · doi:10.31219/osf.io/uf25z · Cited by 2 · see citing works
Kalafut, K. C., Janes, M. E., & Riccio-Ackerman, F. (2022) · MIT Science Policy Review · doi:10.38105/spr.d97k21lnkj · Cited by 1 · see citing works
Kennedy, B. K., Goh, J., & Wong, E. S. P. (2021) · Springer eBooks · doi:10.1007/978-3-030-22009-9_1074 · Cited by 1 · see citing works
Senotherapeutics: Experimental therapy of cellular senescence
Justice, J. N., Niedernhofer, L. J., & Orr, M. E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-815962-0.00012-3
Self-citationTranslational research in the fastest-growing population: older adults
Justice, J. N., High, K. P., & Kritchevsky, S. B. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820493-1.00032-5
Self-citationKennedy, B. K., Goh, J., & Wong, E. S. P. (2020) · Springer eBooks · doi:10.1007/978-3-319-69892-2_1074-1
Palmer, A. K., & Kirkland, J. L. (2022) · Cambridge University Press eBooks · doi:10.1017/9781108942751.002
Chapter 2. Physiological and Clinical Considerations of Geriatric Patient Care
Jaeger, J., & Kuchel, G. A. (2022) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375196.ds02
Self-citationLas intermitencias de la metformina. El boom como terapia antienvejecimiento de un viejo fármaco
Escobar, J. M. T. (2024) · Medicina · doi:10.56050/01205498.2350
Bilder, G. E., & Brown-O’Hara, P. (2025) · Springer eBooks · doi:10.1007/978-3-031-84831-5_10
Metformina: paradigma de pleiotropismo terapéutico (1922-2025)
de Leiva, A., & Morell, F. (2025) · Medicina Clínica · doi:10.1016/j.medcli.2025.107189
Metformin: Paradigm of therapeutic pleiotropism (1922–2025)
de Leiva, A., & Morell, F. (2025) · Medicina Clínica (English Edition) · doi:10.1016/j.medcle.2025.107189
Chenchula, S., Amerneni, K. C., Padmavathi, R., Anitha, K., Ghanta, M. K., Karunakaran, S., Atal, S., Kumar, S., Saggurthi, P., Jenifa, S., et al. (2026) · Inflammopharmacology · doi:10.1007/s10787-026-02218-1
Immunotherapy for senescent cell clearance: Hallmarks, strategies and translational challenges
Zhang, W., Chen, S., & Zhuang, X. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103174
The past, present, and future of Alzheimer's disease—part 3: the future
Nitríni, R., Takada, L. T., & Brucki, S. M. D. (2026) · Arquivos de Neuro-Psiquiatria · doi:10.1055/s-0046-1824435
Huai, W., Ng, L.-F., Lee, J. H., Wang, Q., Pabis, K., Yee, Z., Raventhiran, S., Guan, S.-P., Thein, S., Raj, S. D., et al. (2026) · Science Advances · doi:10.1126/sciadv.aee3657
Majumdar, V., Palanisamy, A., Yadav, A., Dwivedi, R., Tiwari, P., & Dada, R. (2026) · Advances in biogerontology · doi:10.1016/bs.abger.2026.09.002
Bello‐Chavolla, O. Y., & Fermín‐Martínez, C. A. (2026) · Advances in biogerontology · doi:10.1016/bs.abger.2026.08.002
Pinnelli, V. B., Surendra Babu, T., A., J. C., Mathew, H. A., Kandi, V., R., M. G., Sam, K. T., Sucharitha, A. S., Divyadharshini, M. S., Batchu, S. V. C., et al. (2026) · Cureus · doi:10.7759/cureus.117984
- Authors
- Justice, J. N., Niedernhofer, L., Robbins, P. D., Aroda, V. R., Espeland, M. A., Kritchevsky, S. B., Kuchel, G. A., & Barzilai, N.
- Affiliations
- Wake Forest University Health Sciences (US)
- University of Minnesota (US)
- Brigham and Women's Hospital (US)
- Internal Medicine Section on Gerontology and Geriatrics, and the Sticht Center for Healthy Aging and Alzheimer’s Prevention
- University of Connecticut (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Justice, Jamie N.
- ORCID
- Venue
- Cardiovascular Endocrinology & Metabolism
- Published
- 2018-12
- Volume
- 7
- Issue
- 4
- Pages
- 80-83
- ISSN
- 2574-0954 (ISSN-L)
- PMC
- PMC6428447
- OpenAlex
- W2911722517
- Cited by
- 84
- References
- 31
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 7 · 2023: 12 · 2022: 16 · 2021: 12 · 2020: 16 · 2019: 5
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Cardiovascular Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P01AG043376, R01AG052608, R01AG048023, P30AG038072, K01AG059837, U19AG056278, P30AG021332)
- National Institute of General Medical Sciences (R35GM124922)
- National Institute of Allergy and Infectious Diseases (R01AI142086)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Aging and Gerontology Research
- Keywords
- geroscience, healthy lifespan extension, clinical trial design, age-related diseases, biological aging, metformin, consensus building
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