Cited by 355FOXO transcription factor regulationGenetics, Aging, and Longevity in Model OrganismsMuscle Physiology and Disorders

The DOI matches its Crossref record, with a small difference in title or year; 71 of the 71 references it cites were found in a registry or an index.

FOXO3: A Major Gene for Human Longevity - A Mini-Review

Open access

Morris, Brian J., Willcox, Donald Craig, Donlon, Timothy A., Willcox, Bradley J.·2015·Gerontology

DOI 10.1159/000375235PMC PMC5403515

Open this paper in CoChat — free account Open PDF

Abstract

Background: The gene FOXO3, encoding the transcription factor forkhead box O-3 (FoxO3), is one of only two for which genetic polymorphisms have exhibited consistent associations with longevity in diverse human populations. Objective: Here, we review the multitude of actions of FoxO3 that are relevant to health, and thus healthy ageing and longevity. Methods: The study involved a literature search for articles retrieved from PubMed using FoxO3 as keyword. Results: We review the molecular genetics of FOXO3 in longevity, then current knowledge of FoxO3 function relevant to ageing and lifespan. We describe how FoxOs are involved in energy metabolism, oxidative stress, proteostasis, apoptosis, cell cycle regulation, metabolic processes, immunity, inflammation and stem cell maintenance. The single FoxO in Hydra confers immortality to this fresh water polyp, but as more complex organisms evolved, this role has been usurped by the need for FoxO to control a broader range of specialized pathways across a wide spectrum of tissues assisted by the advent of as many as 4 FoxO subtypes in mammals. The major themes of FoxO3 are similar, but not identical, to other FoxOs and include regulation of cellular homeostasis, particularly of stem cells, and of inflammation, which is a common theme of age-related diseases. Other functions concern metabolism, cell cycle arrest, apoptosis, destruction of potentially damaging reactive oxygen species and proteostasis. Conclusions: The mechanism by which longevity-associated alleles of FOXO3 reduce age-related mortality is currently of great clinical interest. The prospect of optimizing FoxO3 activity in humans to increase lifespan and reduce age-related diseases represents an exciting avenue of clinical investigation. Research strategies directed at developing therapeutic agents that target FoxO3, its gene and proteins in the pathway(s) FoxO3 regulates should be encouraged and supported.

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 · 10.1159/000375235

Cites

71 of 71 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?

Self-check

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

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

A C. elegans mutant that lives twice as long as wild type
Kenyon, C., Chang, J., Gensch, E., Rudner, A., & Tabtiang, R. (1993) · Nature · doi:10.1038/366461a0 · Cited by 3,387
The genetics of ageing
Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739
Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans
Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., et al. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.016 · Cited by 2,087
A Mutant Drosophila Insulin Receptor Homolog That Extends Life-Span and Impairs Neuroendocrine Function
Tatar, M., Kopelman, A. H., Epstein, D., Tu, M., Yin, C. ‐., & Garofalo, R. S. (2001) · Science · doi:10.1126/science.1057987 · Cited by 1,630
FoxOs Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress
Tothova, Z., Kollipara, R., Huntly, B. J., Lee, B. H., Castrillon, D. H., Cullen, D. E., McDowell, E. P., Lazo-Kallanian, S., Williams, I. R., Sears, C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.01.003 · Cited by 1,562
Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial
Makkar, R., Smith, R. R., Cheng, K., Malliaras, K. G., Thomson, L., Berman, D. S., Czer, L. S. C., Marbán, L., Mendizabal, A. M., Johnston, P. V., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60195-0 · Cited by 1,423
Mitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure
Liesa, M., & Shirihai, O. S. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.002 · Cited by 1,341
Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue
Blüher, M., Kahn, B. B., & Kahn, C. R. (2003) · Science · doi:10.1126/science.1078223 · Cited by 1,155
Akt, FoxO and regulation of apoptosis
Zhang, X., Tang, N., Hadden, T. J., & Rishi, A. K. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.03.010 · Cited by 1,149
FOXOs: signalling integrators for homeostasis maintenance
Eijkelenboom, A., & Burgering, B. M. T. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3507 · Cited by 1,110

Show all 70 references

Sorted by citations

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
Clinical and molecular aspects of lead toxicity: An update
Mitra, P., Sharma, S., Purohit, P., & Sharma, P. (2017) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408363.2017.1408562 · Cited by 402
Proteomic aging clock predicts mortality and risk of common age-related diseases in diverse populations
Argentieri, M. A., Xiao, S., Bennett, D., Winchester, L. M., Nevado‐Holgado, A. J., Ghose, U., Albukhari, A., Yao, P., Mazidi, M., Lv, J., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-03164-7 · Cited by 421
Therapeutic strategies targeting FOXO transcription factors
Calissi, G., Lam, E. W. ‐., & Link, W. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0088-2 · Cited by 339
FOXO3a from the Nucleus to the Mitochondria: A Round Trip in Cellular Stress Response
Fasano, C., Disciglio, V., Bertora, S., Signorile, M. L., & Simone, C. (2019) · Cells · doi:10.3390/cells8091110 · Cited by 251
DAF-16/FoxO in Caenorhabditis elegans and Its Role in Metabolic Remodeling
Zečić, A., & Braeckman, B. P. (2020) · Cells · doi:10.3390/cells9010109 · Cited by 241
Age-dependent shift in macrophage polarisation causes inflammation-mediated degeneration of enteric nervous system
Becker, L., Nguyen, L., Gill, J., Kulkarni, S., Pasricha, P. J., & Habtezion, A. (2018) · Gut · doi:10.1136/gutjnl-2016-312940 · Cited by 196
TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer’s disease mice
Wang, Y., Lin, Y., Wang, L., Zhan, H., Luo, X., Zeng, Y., Wu, W., Zhang, X., & Wang, F. (2020) · Aging · doi:10.18632/aging.104104 · Cited by 196
Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis
Stojanović, S. D., Fiedler, J., Bauersachs, J., Thum, T., & Sedding, D. G. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz919 · Cited by 188
Short Chain Fatty Acid Metabolism in Relation to Gut Microbiota and Genetic Variability
Meyers, G. R., Samouda, H., & Bohn, T. (2022) · Nutrients · doi:10.3390/nu14245361 · Cited by 208
Characterization of the direct targets of FOXO transcription factors throughout evolution
Webb, A. E., Kundaje, A., & Brunet, A. (2016) · Aging Cell · doi:10.1111/acel.12479 · Cited by 182
Introduction to FOXO Biology
Link, W. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8900-3_1 · Cited by 182
FOXO Transcriptional Factors and Long‐Term Living
Murtaza, G., Khan, A. K., Rashid, R., Muneer, S., Hasan, S. M. F., & Chen, J. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/3494289 · Cited by 182
FOXO transcription factors as therapeutic targets in human diseases
Orea‐Soufi, A., Paik, J., Bragança, J., Donlon, T. A., Willcox, B. J., & Link, W. (2022) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2022.09.010 · Cited by 181
Self-citation
Human longevity: Genetics or Lifestyle? It takes two to tango
Passarino, G., Rango, F. D., & Montesanto, A. (2016) · Immunity & Ageing · doi:10.1186/s12979-016-0066-z · Cited by 192
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 172
A critical review on lead removal from industrial wastewater: Recent advances and future outlook
Kumar, V., Dwivedi, S. K., & Oh, S. (2021) · Journal of Water Process Engineering · doi:10.1016/j.jwpe.2021.102518 · Cited by 165
Recent Advances in Functionalized Nanoparticles in Cancer Theranostics
Siddique, S., & Chow, J. C. L. (2022) · Nanomaterials · doi:10.3390/nano12162826 · Cited by 147
Proteomics in aging research: A roadmap to clinical, translational research
Moaddel, R., Ubaida‐Mohien, C., Tanaka, T., Lyashkov, A., Basisty, N., Schilling, B., Semba, R. D., Franceschi, C., Gorospe, M., & Ferrucci, L. (2021) · Aging Cell · doi:10.1111/acel.13325 · Cited by 139
Leveraging knowledge of HDLs major protein ApoA1: Structure, function, mutations, and potential therapeutics
Bhale, A. S., & Venkataraman, K. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113634 · Cited by 137
FOXO1/3: Potential suppressors of fibrosis
Xin, Z., Ma, Z., Hu, W., Jiang, S., Yang, Z. P., Li, T. X., Chen, F., Jia, G., & Yang, Y. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.11.002 · Cited by 131
Pharmacology of caffeine and its effects on the human body
Reddy, V. S., Shiva, S. M., Manikantan, S., & Ramakrishna, S. (2024) · European Journal of Medicinal Chemistry Reports · doi:10.1016/j.ejmcr.2024.100138 · Cited by 154
Dietary phytochemicals and neuro-inflammaging: from mechanistic insights to translational challenges
Davinelli, S., Maes, M., Corbi, G., Zarrelli, A., Willcox, D. C., & Scapagnini, G. (2016) · Immunity & Ageing · doi:10.1186/s12979-016-0070-3 · Cited by 122
Self-citation
FOXO3-Engineered Human ESC-Derived Vascular Cells Promote Vascular Protection and Regeneration
Yan, P., Li, Q., Wang, L., Lü, P., Suzuki, K., Liu, Z., Lei, J., Li, W., He, X., Wang, S., et al. (2019) · Cell stem cell · doi:10.1016/j.stem.2018.12.002 · Cited by 123
Longevity extension in Drosophila through gut-brain communication
Westfall, S., Lomis, N., & Prakash, S. (2018) · Scientific Reports · doi:10.1038/s41598-018-25382-z · Cited by 113
FOXO family isoforms
Santos, B., Grenho, I., Martel, P. J., Ferreira, B. I., & Link, W. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06177-1 · Cited by 118
Identification and characterization of two functional variants in the human longevity gene FOXO3
Flachsbart, F., Dose, J., Gentschew, L., Geismann, C., Caliebe, A., Knecht, C., Nygaard, M., Badarinarayan, N., ElSharawy, A., May, S., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-02183-y · Cited by 110
Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity
Revelas, M., Thalamuthu, A., Oldmeadow, C. J., Evans, T., Armstrong, N. J., Kwok, J. B., Brodaty, H., Schofield, P. R., Scott, R. J., Sachdev, P. S., et al. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.06.002 · Cited by 96
Genetics of human longevity within an eco-evolutionary nature-nurture framework
Giuliani, C., Garagnani, P., & Franceschi, C. (2018) · Circulation Research · doi:10.1161/circresaha.118.312562 · Cited by 92
Molecular and Cellular Manifestations of Biological Aging of Cochlear Inner and Outer Hair Cells
Liu, H., Giffen, K. P., Chen, L., Henderson, H. J., Cao, T. A., Kozeny, G. A., Beisel, K. W., Li, Y., & He, D. Z. Z. (2021) · Cell Reports · doi:10.1016/j.celrep.2022.110665 · Cited by 94
Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity
Karagiannis, T. T., Dowrey, T. W., Villacorta-Martín, C., Montano, M. A., Reed, E. R., Belkina, A. C., Andersen, S. L., Perls, T. T., Monti, S., Murphy, G. J., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104514 · Cited by 88
Aging Biomarkers: From Functional Tests to Multi‐Omics Approaches
Kudryashova, K. S., Burka, K., Kulaga, A. Y., Vorobyeva, N. S., & Kennedy, B. K. (2020) · PROTEOMICS · doi:10.1002/pmic.201900408 · Cited by 95
Lamin A involvement in ageing processes
Cenni, V., Capanni, C., Mattioli, E., Schena, E., Squarzoni, S., Bacalini, M. G., Garagnani, P., Salvioli, S., Franceschi, C., & Lattanzi, G. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101073 · Cited by 87
Ovarian aging: energy metabolism of oocytes
Bao, S., Yin, T., & Liu, S. (2024) · Journal of Ovarian Research · doi:10.1186/s13048-024-01427-y · Cited by 92
FOXOs: masters of the equilibrium
Gui, T., & Burgering, B. M. T. (2021) · FEBS Journal · doi:10.1111/febs.16221 · Cited by 86
Antiaging effects of bioactive molecules isolated from plants and fungi
Martel, J., Ojcius, D. M., Ko, Y., Chang, C., & Young, J. D. (2019) · Medicinal Research Reviews · doi:10.1002/med.21559 · Cited by 79
Senescence-resistant human mesenchymal progenitor cells counter aging in primates
Lei, J., Xin, Z., Liu, N., Ning, T., Jing, Y., Qiao, Y., He, Z., Jiang, M., Yang, Y., Zhang, Z., et al. (2025) · Cell · doi:10.1016/j.cell.2025.05.021 · Cited by 85
The FoxO3 gene and cause‐specific mortality
Willcox, B. J., Tranah, G. J., Chen, R., Morris, B. J., Masaki, K., He, Q., Willcox, D. C., Allsopp, R., Moisyadi, S., Poon, L. W., et al. (2016) · Aging Cell · doi:10.1111/acel.12452 · Cited by 77
Self-citation
Antioxidant and Antisenescence Effects of Bergamot Juice
Pozzo, E. D., Leo, M. D., Faraone, I., Milella, L., Cavallini, C., Piragine, E., Testai, L., Calderone, V., Pistelli, L., Braca, A., et al. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/9395804 · Cited by 74
The somatotropic axis and longevity in mice
Brown‐Borg, H. M. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00262.2015 · Cited by 74
Functional conservation in genes and pathways linking ageing and immunity
Fabian, D. K., Fuentealba, M., Dönertaş, H. M., Partridge, L., & Thornton, J. M. (2021) · Immunity & Ageing · doi:10.1186/s12979-021-00232-1 · Cited by 75
Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum
Lu, A. T.-H., Hannon, E. J., Levine, M. E., Hao, K., Crimmins, E. M., Lunnon, K., Kozlenkov, A., Mill, J. S., Dracheva, S. M., & Horvath, S. (2016) · Nature Communications · doi:10.1038/ncomms10561 · Cited by 72
Insulin/insulin-like growth factor-1 signalling (IIS) based regulation of lifespan across species
Mathew, R., Bhadra, M. P., & Bhadra, U. (2017) · Biogerontology · doi:10.1007/s10522-016-9670-8 · Cited by 79
Untangling Longevity, Dauer, and Healthspan in Caenorhabditis elegans Insulin/IGF-1-Signalling
Ewald, C. Y., Castillo-Quan, J. I., & Blackwell, T. K. (2017) · Gerontology · doi:10.1159/000480504 · Cited by 70
Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on ageing: Molecular mechanisms
Bahrami, A., Bo, S., Jamialahmadi, T., & Sahebkar, A. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101024 · Cited by 68
Nutritional Programming of Lifespan by FOXO Inhibition on Sugar-Rich Diets
Dobson, A. J., Ezcurra, M., Flanagan, C. E., Summerfield, A. C., Piper, M. D. W., Gems, D., & Alic, N. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.029 · Cited by 63
Nutrients and Pathways that Regulate Health Span and Life Span
Pignatti, C., D’Adamo, S., Stefanelli, C., Flamigni, F., & Cetrullo, S. (2020) · Geriatrics · doi:10.3390/geriatrics5040095 · Cited by 68
To Be Frail or Not to Be Frail: This Is the Question—A Critical Narrative Review of Frailty
Sciacchitano, S., Carola, V., Nicolais, G., Sciacchitano, S., Napoli, C., Mancini, R., Rocco, M., & Coluzzi, F. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13030721 · Cited by 74
Pharmaceutical and nutraceutical activation of FOXO3 for healthy longevity
McIntyre, R. L., Liu, Y. J., Hu, I. M., Morris, B. J., Willcox, B. J., Donlon, T. A., Houtkooper, R. H., & Janssens, G. E. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101621 · Cited by 68
Self-citation
Modulation of gut microbiota and delayed immunosenescence as a result of syringaresinol consumption in middle-aged mice
Cho, S., Kim, J., Lee, J. H., Sim, J. H., Cho, D.-H., Bae, I., Lee, H., Seol, M. A., Shin, H. M., Kim, T.-J., et al. (2016) · Scientific Reports · doi:10.1038/srep39026 · Cited by 67
Astaxanthin as a Putative Geroprotector: Molecular Basis and Focus on Brain Aging
Sorrenti, V., Davinelli, S., Scapagnini, G., Willcox, B. J., Allsopp, R., & Willcox, D. C. (2020) · Marine Drugs · doi:10.3390/md18070351 · Cited by 65
Self-citation
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 63
Demographic, phenotypic, and genetic characteristics of centenarians in Okinawa and Japan: Part 1—centenarians in Okinawa
Willcox, B. J., Willcox, D. C., & Suzuki, M. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.11.001 · Cited by 61
Self-citation
FOXO 3 longevity interactome on chromosome 6
Donlon, T. A., Morris, B. J., Chen, R., Masaki, K., Allsopp, R., Willcox, D. C., Elliott, A., & Willcox, B. J. (2017) · Aging Cell · doi:10.1111/acel.12625 · Cited by 60
Self-citation
Circ-Foxo3 is positively associated with the Foxo3 gene and leads to better prognosis of acute myeloid leukemia patients
Zhou, J., Zhou, L.-Y., Tang, X. M., Zhang, J., Zhai, L.-L., Yi, Y., Yi, J., Lin, J., Qian, J., & Deng, Z. (2019) · BMC Cancer · doi:10.1186/s12885-019-5967-8 · Cited by 59
Over-expression of growth differentiation factor 15 (GDF15) preventing cold ischemia reperfusion (I/R) injury in heart transplantation through Foxo3a signaling
Zhang, Y., Moszczynski, L. A., Liu, Q. H., Jiang, J., Zhao, D., Quan, D., Mele, T. S., McAlister, V. C., Jevnikar, A. M., Baek, S. J., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.16607 · Cited by 60
Neuroprotective mechanisms of ε-viniferin in a rotenone-induced cell model of Parkinson's disease: significance of SIRT3-mediated FOXO3 deacetylation
Zhang, S., Ma, Y., & Feng, J. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.282264 · Cited by 61
Research Progress on the Anti-Aging Potential of the Active Components of Ginseng
Su, J., Su, Q., Hu, S., Ruan, X., & Ouyang, S. (2023) · Nutrients · doi:10.3390/nu15153286 · Cited by 58
Gain-of-function mutant p53 promotes the oncogenic potential of head and neck squamous cell carcinoma cells by targeting the transcription factors FOXO3a and FOXM1
Tanaka, N., Zhao, M., Tang, L., Patel, A. A., Xi, Q., Van, H. T., Takahashi, H., Osman, A. A., Zhang, J., Wang, J., et al. (2017) · Oncogene · doi:10.1038/s41388-017-0032-z · Cited by 60
Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging
Jing, Y., Zuo, Y., Yu, Y., Sun, L., Yu, Z., Ma, S., Zhao, Q., Sun, G., Hu, H., Li, J., et al. (2022) · Protein & Cell · doi:10.1093/procel/pwac061 · Cited by 59
Posttranscriptional regulation of FOXO expression: microRNAs and beyond
Urbánek, P., & Klotz, L. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13471 · Cited by 56
FOXO transcription factors in non-alcoholic fatty liver disease
Dong, X. C. (2017) · Liver Research · doi:10.1016/j.livres.2017.11.004 · Cited by 64
Age associated non-linear regulation of redox homeostasis in the anucleate platelet: Implications for CVD risk patients
Jain, K., Tyagi, T., Patell, K., Xie, Y., Kadado, A. J., Lee, S. H., Yarovinsky, T. O., Du, J., Hwang, J. J., Martin, K. A., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.05.022 · Cited by 60
A small-molecule inhibitor of PCSK9 transcription ameliorates atherosclerosis through the modulation of FoxO1/3 and HNF1α
Wang, X., Chen, X., Zhang, X., Su, C., Yang, M., He, W., Du, Y., Si, S., Wang, L., & Hong, B. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102650 · Cited by 58
Berberine protects against ischemia/reperfusion injury after orthotopic liver transplantation via activating Sirt1/FoxO3α induced autophagy
Lin, Y., Sheng, M., Weng, Y., Xu, R., Lü, N., Du, H., & Yu, W. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.01.028 · Cited by 57
ApoE4 attenuates autophagy via FoxO3a repression in the brain
Sohn, H.-Y., Kim, S.-I., Park, J.-Y., Park, S.-H., Koh, Y. H., Kim, J., & Jo, C. (2021) · Scientific Reports · doi:10.1038/s41598-021-97117-6 · Cited by 54
Growth factor, energy and nutrient sensing signalling pathways in metabolic ageing
Bettedi, L., & Foukas, L. C. (2017) · Biogerontology · doi:10.1007/s10522-017-9724-6 · Cited by 55
1,25-Dihydroxyvitamin D and Klotho
Haussler, M. R., Whitfield, G. K., Haussler, C. A., Sabir, M. S., Khan, Z., Sandoval, R., & Jurutka, P. W. (2016) · Vitamins and hormones · doi:10.1016/bs.vh.2015.11.005 · Cited by 54
Enlightening discriminative network functional modules behind Principal Component Analysis separation in differential-omic science studies
Ciucci, S., Ge, Y., Durán, C., Palladini, A., Jiménez-Jiménez, V., Martínez-Sánchez, L. M., Wang, Y., Sales, S., Shevchenko, A., Poser, S., et al. (2017) · Scientific Reports · doi:10.1038/srep43946 · Cited by 55
Metformin Attenuates ROS via FOXO3 Activation in Immune Cells
Hartwig, J., Löbel, M., Steiner, S., Bauer, S., Karadeniz, Z., Roeger, C., Skurk, C., Scheibenbogen, C., & Sotzny, F. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.581799 · Cited by 54
Metabolic Regulation of Angiogenesis in Diabetes and Aging
Sawada, N., & Arany, Z. P. (2017) · Physiology · doi:10.1152/physiol.00039.2016 · Cited by 55
Circular RNAs: New players in thyroid cancer
Borran, S., Ahmadi, G., Rezaei, S., Anari, M. M., Modabberi, M., Azarash, Z., Razaviyan, J., Derakhshan, M., Akhbari, M., & Mirzaei, H. (2020) · Pathology - Research and Practice · doi:10.1016/j.prp.2020.153217 · Cited by 52
Emerging contaminant 1,3,6,8-tetrabromocarbazole induces oxidative damage and apoptosis during the embryonic development of zebrafish (Danio rerio)
Zhang, J., Zhang, C., Du, Z., Zhu, L., Wang, J., Wang, J., & Li, B. J. (2020) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2020.140753 · Cited by 51
Dysregulated Autophagy Mediates Sarcopenic Obesity and Its Complications via AMPK and PGC1α Signaling Pathways: Potential Involvement of Gut Dysbiosis as a Pathological Link
Ryu, J. Y., Choi, H. M., Yang, H.-I., & Kim, K. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186887 · Cited by 52
Improving DNA nanostructure stability: A review of the biomedical applications and approaches
Nasiri, M., Bahadorani, M., Dellinger, K., Aravamudhan, S., Vivero-Escoto, J. L., & Zadegan, R. M. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.129495 · Cited by 51
Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction
Jiang, Y.-Z., Yan, F., Feng, Z., Lazarovici, P., & Zheng, W. (2019) · Cells · doi:10.3390/cells9010100 · Cited by 51
The Microbiome Mediates Environmental Effects on Aging
Finlay, B. B., Pettersson, S., Melby, M. K., & Bosch, T. C. G. (2019) · BioEssays · doi:10.1002/bies.201800257 · Cited by 48
Immune mechanisms of group B coxsackievirus induced viral myocarditis
Zhang, Y., Zhou, X., Chen, S., Sun, X., & Zhou, C. (2023) · Virulence · doi:10.1080/21505594.2023.2180951 · Cited by 48
MicroRNA-221 silencing attenuates the degenerated phenotype of intervertebral disc cells
Penolazzi, L., Lambertini, E., Bergamin, L. S., Roncada, T., BONIS, P. D., Cavallo, M. A., & Piva, R. (2018) · Aging · doi:10.18632/aging.101525 · Cited by 45
Transcriptomic and Network Analysis Highlight the Association of Diabetes at Different Stages of Alzheimer’s Disease
Santiago, J. A., Bottero, V., & Potashkin, J. A. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01273 · Cited by 43
Dysregulation of DAF-16/FOXO3A-mediated stress responses accelerates oxidative DNA damage induced aging
Gurkar, A. U., Robinson, A. R., Cui, Y., Li, X., Allani, S. K., Webster, A., Muravia, M., Fallahi, M., Weissbach, H., Robbins, P. D., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2018.06.005 · Cited by 44
The impact of a novel Chinese yam -derived polysaccharide on blood glucose control in HFD and STZ-induced diabetic C57BL/6 mice
Feng, X., Zhang, Q., Li, J., Bie, N., Li, C., Lian, R., Qin, L., Feng, Y., & Wang, C. (2022) · Food & Function · doi:10.1039/d1fo03830c · Cited by 43
Keeping Neurons Young and Foxy: FoxOs Promote Neuronal Plasticity
McLaughlin, C. N., & Broihier, H. T. (2017) · Trends in Genetics · doi:10.1016/j.tig.2017.10.002 · Cited by 46
Effects of Fisetin, a Plant-Derived Flavonoid, on Response to Oxidative Stress, Aging, and Age-Related Diseases in Caenorhabditis elegans
Park, S.-H., Kim, B.-K., & Park, S.-K. (2022) · Pharmaceuticals · doi:10.3390/ph15121528 · Cited by 43
Effects of FOXO3 Polymorphisms on Survival to Extreme Longevity in Four Centenarian Studies
Bae, H. T., Gurinovich, A., Malovini, A. L., Atzmon, G., Andersen, S. L., Villa, F., Barzilai, N., Puca, A. A., Perls, T. T., & Sebastiani, P. (2017) · The Journals of Gerontology Series A · doi:10.1093/gerona/glx124 · Cited by 41
Structure, Activity and Function of the Protein Arginine Methyltransferase 6
Gupta, S., Kadumuri, R. V., Singh, A. K., Chavali, S., & Dhayalan, A. (2021) · Life · doi:10.3390/life11090951 · Cited by 40
Extracellular vesicles derived from mesenchymal stem cells confer protection against intervertebral disc degeneration through a microRNA-217-dependent mechanism
Hao, Y., Zhu, G., Li, Y., Ren, Z., Zhang, P., Zhu, J. H., & Cao, S. (2022) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2022.08.009 · Cited by 40
Signal Transduction, Ageing and Disease
Zhang, L. J., Yousefzadeh, M. J., Suh, Y., Niedernhofer, L. J., & Robbins, P. D. (2019) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-3681-2_9 · Cited by 40
Oral oyster polypeptides protect ovary against d ‐galactose‐induced premature ovarian failure in C57BL/6 mice
Li, Y., Qiu, W., Zhang, Z., Han, X., Bu, G., Meng, F., Kong, F., Cao, X., Huang, A., Feng, Z., et al. (2019) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.9997 · Cited by 39
Polystyrene Nanoplastics Induce Lung Injury via Activating Oxidative Stress: Molecular Insights from Bioinformatics Analysis
Zhang, T., Yang, S., Ge, Y., Wan, X., Zhu, Y., Li, J., Yin, L., Pu, Y., & Liang, G. (2022) · Nanomaterials · doi:10.3390/nano12193507 · Cited by 42
Aryl hydrocarbon receptor (AhR) impairs circadian regulation: Impact on the aging process
Salminen, A. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101928 · Cited by 42
Role of Forkhead box O3a transcription factor in autoimmune diseases
Xu, S., Ma, Y., Chen, Y., & Pan, F. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2020.107338 · Cited by 39
Nuclear FOXO3 predicts adverse clinical outcome and promotes tumor angiogenesis in neuroblastoma
Hagenbuchner, J., Rupp, M., Salvador, C., Meister, B., Kiechl‐Kohlendorfer, U., Müller, T., Geiger, K., Sergi, C. M., Obexer, P., & Ausserlechner, M. J. (2016) · Oncotarget · doi:10.18632/oncotarget.12728 · Cited by 39
Adrenomedullin/ FOXO3 enhances sunitinib resistance in clear cell renal cell carcinoma by inhibiting FDX1 expression and cuproptosis
Wang, X., Jia, J., Zhang, M., Meng, Q., Yan, B., Ma, Z., & Wang, D. (2023) · The FASEB Journal · doi:10.1096/fj.202300474r · Cited by 37
Multiomics Provides Insights into the Impacts of Microplastics on Heavy Metal(Loid) Accumulation in Lettuce under Simulated Acid Precipitation
Chen, L., Chang, N., Liu, H., Li, T., Huang, F., Zeng, Y., He, H., Qiu, T., Xu, Y., Peng, L., et al. (2025) · ACS Sustainable Chemistry & Engineering · doi:10.1021/acssuschemeng.5c03114 · Cited by 37
Longevity is determined by ETS transcription factors in multiple tissues and diverse species
Dobson, A. J., Boulton-McDonald, R., Houchou, L., Svermova, T., Ren, Z., Subrini, J., Vazquez-Prada, M., Hoti, M., Rodríguez‐López, M., Ibrahim, R., et al. (2019) · PLoS Genetics · doi:10.1371/journal.pgen.1008212 · Cited by 37
Role of Oxidative Stress in the Senescence Pattern of Auditory Cells in Age-Related Hearing Loss
Chacón, L. D. M. R., Martínez-Rodríguez, S., Madrid, R., Yanes‐Diaz, J., Riestra‐Ayora, J., Fernández, R. S., & Sánchez‐Rodríguez, C. (2021) · Antioxidants · doi:10.3390/antiox10091497 · Cited by 37
Cell Survival, Death, and Proliferation in Senescent and Cancer Cells: the Role of (Poly)phenols
Sorrenti, V., Buriani, A., Fortinguerra, S., Davinelli, S., Scapagnini, G., Cassidy, A., & Vivo, I. D. (2023) · Advances in Nutrition · doi:10.1016/j.advnut.2023.05.014 · Cited by 38
FOXO3 and Exceptional Longevity: Insights From Hydra to Humans
Davy, P. M. C., Allsopp, R., Donlon, T. A., Morris, B. J., Willcox, D. C., & Willcox, B. J. (2018) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2017.10.001 · Cited by 39
Self-citation
Whole Genome DNA Methylation Analysis of Active Pulmonary Tuberculosis Disease Identifies Novel Epigenotypes: PARP9/miR-505/RASGRP4/GNG12 Gene Methylation and Clinical Phenotypes
Chen, Y., Hsiao, C., Chen, T.-W., Wu, C., Chao, T.-Y., Leung, S., Eng, H.-L., Lee, C., Wang, T.-Y., & Lin, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093180 · Cited by 36

Authors: Morris, B. J., Willcox, D. C., Donlon, T. A., & Willcox, B. J.
Affiliations: University of Hawaiʻi at Mānoa (US)
Kuakini Medical Center (US)
ORCID: Morris, Brian J.
Donlon, Timothy A.
Willcox, Bradley J.
Venue: Gerontology
Publisher: S. Karger AG
Published: 2015
Volume: 61
Issue: 6
Pages: 515-525
ISSN: 0304-324X (ISSN-L)
1423-0003
DOI: 10.1159/000375235
PMC: PMC5403515
OpenAlex: W2058381071
Cited by: 353
References: 70
Citations by year: 2026: 25 · 2025: 32 · 2024: 44 · 2023: 39 · 2022: 45 · 2021: 34 · 2020: 33 · 2019: 26 · 2018: 22 · 2017: 29 · 2016: 20 · 2015: 4
FWCI: 2.42
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.karger.com/Services/SiteLicenses (vor)
www.karger.com/Services/SiteLicenses (tdm)
Locations: Gerontology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (5r01ag038707-04, 5R01AG038707)
National Institute on Aging (5R01AG038707, R01-AG-038707, R01AG027060)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords: FOXO3, human longevity, healthy aging, genetic polymorphism, age-related diseases, oxidative stress, proteostasis, apoptosis, cell cycle regulation, stem cell maintenance, inflammation, energy metabolism, Hydra, lifespan
MeSH terms: Forkhead Box Protein O3, Animals, Humans, Longevity, Forkhead Transcription Factors

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

FOXO3: A Major Gene for Human Longevity - A Mini-Review

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks