The search for DAF-16/FOXO transcriptional targets: Approaches and discoveries
Abstract
The insulin/IGF-1 receptor (IIR)/FOXO pathway is remarkably conserved in worms, flies, and mammals, and downregulation of signaling in this pathway has been shown to extend lifespan in all of these animals. FOXO-mediated transcription is required for the long lifespan of IIR mutants; thus, there is great interest in identifying FOXO target genes, as they may carry out the biochemical activities that extend longevity. A number of approaches have been used to identify the transcriptional targets of FOXO. Thus far, the best data available on the components downstream of this pathway are from experiments involving the Caenorhabditis elegans FOXO transcription factor, DAF-16; some of these targets have been tested for their contributions to longevity, dauer formation, and fat storage. Here, I examine and compare the approaches used to identify DAF-16/FOXO targets, review the genes regulated by DAF-16, and discuss the processes that may be at work to extend lifespan in IIR mutants. Rather than upregulating every possible beneficial gene, DAF-16 appears to selectively upregulate genes that contribute to specific protective mechanisms, while simultaneously downregulating potentially deleterious genes. In addition to genes that carry out expected roles in stress protection, many previously unknown targets have been identified in these studies, suggesting that some mechanisms of lifespan extension still await discovery. These mechanisms may act cooperatively or cumulatively to increase longevity, and are likely to be at least partially conserved in higher organisms.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Transcriptional targets of daf-16 include enzymes involved in metabolism and stress resistance.
“Interestingly, the transcriptional targets of daf-16 include a number of enzymes that are involved in metabolism as well as stress resistance 91 .”
From The common biology of cancer and ageing (2007) · cites this paper as [91]
Foxo3 controls expression of multiple genes involved in stress resistance and metabolism.
“The closest mammalian orthologue of daf-16 is Foxo3, and there is evidence that this mammalian transcription factor also controls the expression of multiple genes involved in stress resistance and metabolism 91 .”
From The common biology of cancer and ageing (2007) · cites this paper as [91]
Cites
Cluster analysis and display of genome-wide expression patterns
Eisen, M. B., Spellman, P. T., Brown, P. O., & Botstein, D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14863 · Cited by 12,617 · see citing works
In silico prediction of protein-protein interactions in human macrophages
Souiai, O., Guerfali, F. Z., Miled, S. B., Brun, C., & Benkahla, A. (2014) · BMC Research Notes · doi:10.1186/1756-0500-7-157 · Cited by 10,785 · see citing works
Significance analysis of microarrays applied to the ionizing radiation response
Tusher, V. G., Tibshirani, R., & Chu, G. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.091062498 · Cited by 10,568 · see citing works
Genome Sequence of the Nematode C. elegans : A Platform for Investigating Biology
Berg, J. (1998) · Science · doi:10.1126/science.282.5396.2012 · Cited by 4,458 · see citing works
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 · see citing works
Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239 · see citing works
Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
Murphy, C. T., McCarroll, S. A., Bargmann, C. I., Fraser, A., Kamath, R. S., Ahringer, J., Li, H., & Kenyon, C. (2003) · Nature · doi:10.1038/nature01789 · Cited by 2,280 · see citing works
Self-citationOgg, S., Paradis, S., Gottlieb, S., Patterson, G. I., Lee, L., Tissenbaum, H. A., & Ruvkun, G. (1997) · Nature · doi:10.1038/40194 · Cited by 1,935 · see citing works
Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
Tissenbaum, H. A., & Guarente, L. (2001) · Nature · doi:10.1038/35065638 · Cited by 1,918 · see citing works
Functional genomic analysis of C. elegans chromosome I by systematic RNA interference
Fraser, A. G., Kamath, R. S., Zipperlen, P., Martinez-Campos, M., Sohrmann, M., & Ahringer, J. (2000) · Nature · doi:10.1038/35042517 · Cited by 1,720 · see citing works
Regulation of aging and age-related disease by DAF-16 and heat-shock factor
Hsu, A.-L., Murphy, C. T., & Kenyon, C. (2003) · Science · doi:10.1126/science.1083701 · Cited by 1,513 · see citing works
Self-citationExtended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue
Blüher, M., Kahn, B. B., & Kahn, C. R. (2003) · Science · doi:10.1126/science.1078223 · Cited by 1,348 · see citing works
FOXO transcription factors at the interface between longevity and tumor suppression
Greer, E. L., & Brunet, A. (2005) · Oncogene · doi:10.1038/sj.onc.1209086 · Cited by 1,306 · see citing works
Genomic binding sites of the yeast cell-cycle transcription factors SBF and MBF
Iyer, V. R., Horak, C. E., Scafe, C., Botstein, D., Snyder, M. P., & Brown, P. O. (2001) · Nature · doi:10.1038/35054095 · Cited by 1,084 · see citing works
Riddle, D. L., Blumenthal, T., Meyer, B. J., & Priess, J. R. (1998) · Cited by 1,047 · see citing works
Lin, K., Hsin, H., Libina, N., & Kenyon, C. J. (2001) · Nature Genetics · doi:10.1038/88850 · Cited by 1,027 · see citing works
Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes
Ashrafi, K., Chang, F., Watts, J. L., Fraser, A. G., Kamath, R. S., Ahringer, J., & Ruvkun, G. (2003) · Nature · doi:10.1038/nature01279 · Cited by 972 · see citing works
Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body
Hwangbo, D., Gersham, B., Tu, M., Palmer, M., & Tatar, M. (2004) · Nature · doi:10.1038/nature02549 · Cited by 954 · see citing works
Henderson, S. T., & Johnson, T. E. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00594-2 · Cited by 949 · see citing works
Morris, J. Z., Tissenbaum, H. A., & Ruvkun, G. (1996) · Nature · doi:10.1038/382536a0 · Cited by 891 · see citing works
A Conserved MST-FOXO Signaling Pathway Mediates Oxidative-Stress Responses and Extends Life Span
Lehtinen, M. K., Yuan, Z., Boag, P. R., Yang, Y., Villén, J., Becker, E. B. E., DiBacco, S., de la Iglesia, N., Gygi, S. P., Blackwell, T. K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.03.046 · Cited by 842 · see citing works
Tissue-Specific Activities of C. elegans DAF-16 in the Regulation of Lifespan
Libina, N., Berman, J. R., & Kenyon, C. (2003) · Cell · doi:10.1016/s0092-8674(03)00889-4 · Cited by 820 · see citing works
van Helden, J., André, B., & Collado‐Vides, J. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.1947 · Cited by 748 · see citing works
Functional Interaction Between ß-Catenin and FOXO in Oxidative Stress Signaling
Essers, M. A. G., Smits, L. M. M., Barker, N., Polderman, P. E., Burgering, B. M. T., & Korswagen, H. C. (2005) · Science · doi:10.1126/science.1109083 · Cited by 741 · see citing works
Honda, Y., & Honda, S. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.11.1385 · Cited by 730 · see citing works
Promoter-specific binding of Rap1 revealed by genome-wide maps of protein–DNA association
Lieb, J. D., Liu, X., Botstein, D., & Brown, P. O. (2001) · Nature Genetics · doi:10.1038/ng569 · Cited by 707 · see citing works
Jia, K., Chen, D., & Riddle, D. L. (2004) · Development · doi:10.1242/dev.01255 · Cited by 705 · see citing works
Impey, S., McCorkle, S., Cha‐Molstad, H., Dwyer, J. M., Yochum, G. S., Boss, J. M., McWeeney, S. K., Dunn, J. J., Mandel, G., & Goodman, R. H. (2004) · Cell · doi:10.1016/j.cell.2004.10.032 · Cited by 695 · see citing works
Regulation of C. elegans Life-Span by Insulinlike Signaling in the Nervous System
Wolkow, C. A., Kimura, K. D., Lee, M. S., & Ruvkun, G. (2000) · Science · doi:10.1126/science.290.5489.147 · Cited by 681 · see citing works
Furuyama, T., Nakazawa, T., Nakano, I., & Mori, N. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3490629 · Cited by 672 · see citing works
DAF-16 Target Genes That Control <i>C. elegans</i> Life-Span and Metabolism
Lee, S. S., Kennedy, S., Tolonen, A. C., & Ruvkun, G. (2003) · Science · doi:10.1126/science.1083614 · Cited by 669 · see citing works
A Gene Expression Map for Caenorhabditis elegans
Kim, S. K., Lund, J., Kiraly, M., Duke, K., Jiang, M., Stuart, J. M., Eizinger, A., Wylie, B., & Davidson, G. S. (2001) · Science · doi:10.1126/science.1061603 · Cited by 658 · see citing works
Pierce, S. B., Costa, M. A., Wisotzkey, R. G., Devadhar, S., Homburger, S. A., Buchman, A. R., Ferguson, K. C., Heller, J., Platt, D., Pasquinelli, A. E., et al. (2001) · Genes & Development · doi:10.1101/gad.867301 · Cited by 639 · see citing works
Puig, Ó., Marr, M. T., Ruhf, M.-L., & Tjian, R. (2003) · Genes & Development · doi:10.1101/gad.1098703 · Cited by 612 · see citing works
Hansen, M., Hsu, A., Dillin, A. G., & Kenyon, C. J. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010017 · Cited by 533 · see citing works
Oh, S. W., Mukhopadhyay, A., Svrzikapa, N., Jiang, F., Davis, R. J., & Tissenbaum, H. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500749102 · Cited by 531 · see citing works
A systematic RNAi screen for longevity genes in C. elegansPreprint
Hamilton, B., Dong, Y., Shindo, M., Liu, W., Odell, I., Ruvkun, G., & Lee, S. S. (2005) · Genes & Development · doi:10.1101/gad.1308205 · Cited by 513 · see citing works
Inducible Antibacterial Defense System in C. elegans
Mallo, G. V., Kurz, C. L., Couillault, C., Pujol, N., Granjeaud, S., Kohara, Y., & Ewbank, J. J. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00928-4 · Cited by 478 · see citing works
Timing Requirements for Insulin/IGF-1 Signaling in C. elegans
Dillin, A., Crawford, D. K., & Kenyon, C. J. (2002) · Science · doi:10.1126/science.1074240 · Cited by 467 · see citing works
McCarroll, S. A., Murphy, C. T., Zou, S., Pletcher, S. D., Chin, C.-S., Jan, Y. N., Kenyon, C., Bargmann, C. I., & Li, H. (2004) · Nature Genetics · doi:10.1038/ng1291 · Cited by 454 · see citing works
Self-citationGenetic and Environmental Regulation of Dauer Larva DevelopmentPreprint
Riddle, D. L., & Albert, P. S. (1997) · Cold Spring Harbor Monograph Archive · doi:10.1101/087969532.33.739 · Cited by 453 · see citing works
A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR
Ramaswamy, S., Nakamura, N., Sansal, I., Bergeron, L., & Sellers, W. R. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00086-7 · Cited by 428 · see citing works
Transcriptional outputs of the <i>Caenorhabditis elegans</i> forkhead protein DAF‐16
McElwee, J., Bubb, K., & Thomas, J. H. (2003) · Aging Cell · doi:10.1046/j.1474-9728.2003.00043.x · Cited by 416 · see citing works
Increased Life-Span of age -1 Mutants in Caenorhabditis elegans and Lower Gompertz Rate of Aging
Johnson, T. E. (1990) · Science · doi:10.1126/science.2392681 · Cited by 414 · see citing works
McElwee, J. J., Schuster, E. F., Blanc, E., Thomas, J. H., & Gems, D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406207200 · Cited by 402 · see citing works
Oh, S. W., Mukhopadhyay, A., Dixit, B. L., Raha, T., Green, M. R., & Tissenbaum, H. A. (2005) · Nature Genetics · doi:10.1038/ng1723 · Cited by 374 · see citing works
Transcriptional feedback control of insulin receptor by dFOXO/FOXO1Preprint
Puig, Ó., & Tjian, R. (2005) · Genes & Development · doi:10.1101/gad.1340505 · Cited by 361 · see citing works
O’Brien, R. M., Lucas, P. C., Forest, C. D., Magnuson, M. A., & Granner, D. K. (1990) · Science · doi:10.1126/science.2166335 · Cited by 357 · see citing works
Insulin regulation of heart function in aging fruit flies
Wessells, R. J., Fitzgerald, E., Cypser, J. R., Tatar, M., & Bodmer, R. (2004) · Nature Genetics · doi:10.1038/ng1476 · Cited by 319 · see citing works
Global analysis of dauer gene expression inCaenorhabditis elegans
Wang, J., & Kim, S. K. (2003) · Development · doi:10.1242/dev.00363 · Cited by 313 · see citing works
Longevity and heavy metal resistance in daf‐2 and age‐1 long‐lived mutants of Caenorhabditis elegans
Barsyte, D., Lovejoy, D. A., & Lithgow, G. J. (2001) · The FASEB Journal · doi:10.1096/fj.99-0966com · Cited by 270 · see citing works
Bussemaker, H. J., Li, H., & Siggia, E. D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.180265397 · Cited by 257 · see citing works
Baugh, L. R., & Sternberg, P. W. (2006) · Current Biology · doi:10.1016/j.cub.2006.03.021 · Cited by 249 · see citing works
Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expressionPreprint
Halaschek-Wiener, J., Khattra, J. S., McKay, S., Pouzyrev, A. T., Stott, J. M., Yang, G., Holt, R. A., Jones, S. J. M., Marra, M. A., Brooks-Wilson, A. R., et al. (2005) · Genome Research · doi:10.1101/gr.3274805 · Cited by 207 · see citing works
SMK-1, an Essential Regulator of DAF-16-Mediated Longevity
Wolff, S., Ma, H., Burch, D., Maciel, G. A. R., Hunter, T. R., & Dillin, A. G. (2006) · Cell · doi:10.1016/j.cell.2005.12.042 · Cited by 205 · see citing works
Lamitina, S. T., & Strange, K. B. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00451.2004 · Cited by 155 · see citing works
Lack of Peroxisomal Catalase Causes a Progeric Phenotype in Caenorhabditis elegans
Petriv, O. I., & Rachubinski, R. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400207200 · Cited by 148 · see citing works
Heat Shock Protein Accumulation Is Upregulated in a Long-Lived Mutant of Caenorhabditis elegans
Walker, G. A., White, T. M., McColl, G., Jenkins, N. L., Babich, S. L., Candido, E. P. M., Johnson, T. E., & Lithgow, G. J. (2001) · The Journals of Gerontology Series A · doi:10.1093/gerona/56.7.b281 · Cited by 135 · see citing works
A Metabolic Model for Life Span Determination in Caenorhabditis elegans
Rea, S. L., & Johnson, T. E. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00242-9 · Cited by 111 · see citing works
Microarray analysis of gene expression with age in individual nematodes
Golden, T. R., & Melov, S. (2004) · Aging Cell · doi:10.1111/j.1474-9728.2004.00095.x · Cited by 109 · see citing works
Mapping DNA-protein interactions in large genomes by sequence tag analysis of genomic enrichment
Kim, J., Bhinge, A., Morgan, X. C., & Iyer, V. R. (2004) · Nature Methods · doi:10.1038/nmeth726 · Cited by 103 · see citing works
Ookuma, S., Fukuda, M., & Nishida, E. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00108-8 · Cited by 82 · see citing works
Nutrient Availability and Growth: Regulation of Insulin Signaling by dFOXO/FOXO1
Puig, Ó., & Tjian, R. (2006) · Cell Cycle · doi:10.4161/cc.5.5.2501 · Cited by 81 · see citing works
The C. elegans lethal gut-obstructed gob-1 gene is trehalose-6-phosphate phosphatase
Kormish, J. D., & McGhee, J. D. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2005.08.027 · Cited by 77 · see citing works
Yu, H. M., & Larsen, P. L. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.5210 · Cited by 67 · see citing works
Enrichment of regulatory motifs upstream of predicted DAF-16 targets
Kenyon, C. J., & Murphy, C. T. (2006) · Nature Genetics · doi:10.1038/ng0406-397 · Cited by 21 · see citing works
Self-citationMicroarray analysis of gene expression
Hunsberger, J. G., & Newton, S. S. (2007) · Protocol Exchange · doi:10.1038/nprot.2007.509 · Cited by 14 · see citing works
Using whole-genome transcriptional analyses to identify molecular mechanisms of aging
Murphy, C. T. (2006) · Drug Discovery Today Disease Mechanisms · doi:10.1016/j.ddmec.2006.02.012 · Cited by 11 · see citing works
Self-citationMiles, E., Miles, M. E., Miles, P. T. R., & Miles, T. R. (2010) · Taylor & Francis eBooks · doi:10.4324/9780203379806_chapter_5 · Cited by 2 · see citing works
Flagged first, then by citations
1 of the 70 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The common biology of cancer and ageing
Finkel, T., Serrano, M., & Blasco, M. A. (2007) · Nature · doi:10.1038/nature05985 · Cited by 988 · see citing works
FOXO3A genotype is strongly associated with human longevity
Willcox, B. J., Donlon, T. A., He, Q., Chen, R., Grove, J. S., Yano, K., Masaki, K. H., Willcox, D. C., Rodriguez, B., & Curb, J. D. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801030105 · Cited by 983 · see citing works
Insulin/insulin-like growth factor signaling in C. elegans
Murphy, C. T. (2013) · WormBook · doi:10.1895/wormbook.1.164.1 · Cited by 527 · see citing works
Self-citationmTOR in aging, metabolism, and cancer
Cornu, M., Albert, V., & Hall, M. N. (2013) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2012.12.005 · Cited by 446 · see citing works
Transcriptional and epigenetic regulation of autophagy in aging
Lapierre, L. R., Kumsta, C., Sandri, M., Ballabio, A., & Hansen, M. (2015) · Autophagy · doi:10.1080/15548627.2015.1034410 · Cited by 339 · see citing works
Lessons from C. elegans: signaling pathways for longevity
Lapierre, L. R., & Hansen, M. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.07.007 · Cited by 331 · see citing works
Lu, T., & Finkel, T. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.01.011 · Cited by 327 · see citing works
Tepper, R. G., Ashraf, J. M., Kaletsky, R. L., Kleemann, G. A., Murphy, C. T., & Bussemaker, H. J. (2013) · Cell · doi:10.1016/j.cell.2013.07.006 · Cited by 308 · see citing works
Self-citationSomatotropic Signaling: Trade-Offs Between Growth, Reproductive Development, and Longevity
Bartke, A., Sun, L. Y., & Longo, V. D. (2013) · Physiological Reviews · doi:10.1152/physrev.00006.2012 · Cited by 286 · see citing works
Russell, J. J., Theriot, J. A., Sood, P., Marshall, W. F., Landweber, L. F., Fritz‐Laylin, L. K., Polka, J., Oliferenko, S., Gerbich, T. M., Gladfelter, A. S., et al. (2017) · BMC Biology · doi:10.1186/s12915-017-0391-5 · Cited by 224 · see citing works
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 224 · see citing works
Insulin signaling promotes germline proliferation in C. elegans
Michaelson, D., Korta, D. Z., Capua, Y., & Hubbard, E. J. A. (2010) · Development · doi:10.1242/dev.042523 · Cited by 209 · see citing works
Out Cold: Biochemical Regulation of Mammalian Hibernation – A Mini-Review
Storey, K. B. (2009) · Gerontology · doi:10.1159/000228829 · Cited by 193 · see citing works
Insulin/IGF-1 paradox of aging: Regulation via AKT/IKK/NF-κB signaling
Salminen, A., & Kaarniranta, K. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2009.10.006 · Cited by 177 · see citing works
Genome-Wide Scan Informed by Age-Related Disease Identifies Loci for Exceptional Human Longevity
Fortney, K., Dobriban, E., Garagnani, P., Pirazzini, C., Monti, D., Mari, D., Atzmon, G., Barzilai, N., Franceschi, C., Owen, A. B., et al. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005728 · Cited by 174 · see citing works
Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans
Portal‐Celhay, C., Bradley, E., & Blaser, M. J. (2012) · BMC Microbiology · doi:10.1186/1471-2180-12-49 · Cited by 166 · see citing works
Insulin/IGF1 Signaling Inhibits Age-Dependent Axon Regeneration
Byrne, A. B., Walradt, T. J., Gardner, K. E., Hubbert, A., Reinke, V., & Hammarlund, M. (2014) · Neuron · doi:10.1016/j.neuron.2013.11.019 · Cited by 158 · see citing works
Heidler, T., Hartwig, K., Daniel, H., & Wenzel, U. (2009) · Biogerontology · doi:10.1007/s10522-009-9239-x · Cited by 156 · see citing works
Integrating the stress response: lessons for neurodegenerative diseases from C. elegans
Prahlad, V., & Morimoto, R. I. (2008) · Trends in Cell Biology · doi:10.1016/j.tcb.2008.11.002 · Cited by 134 · see citing works
The genetics of human longevity: an intricacy of genes, environment, culture and microbiome
Dato, S., Rose, G., Crocco, P., Monti, D., Garagnani, P., Franceschi, C., & Passarino, G. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.03.011 · Cited by 134 · see citing works
Autophagy - An Emerging Anti-Aging Mechanism?
Hansen, M. (2012) · Journal of Clinical & Experimental Pathology · doi:10.4172/2161-0681.s4-006 · Cited by 129 · see citing works
C. elegans rrf-1 Mutations Maintain RNAi Efficiency in the Soma in Addition to the Germline
Kumsta, C., & Hansen, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035428 · Cited by 129 · see citing works
Vitellogenins - Yolk Gene Function and Regulation in Caenorhabditis elegans
Perez, M. F., & Lehner, B. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01067 · Cited by 128 · see citing works
Xenobiotic metabolism and transport in Caenorhabditis elegans
Hartman, J. H., Widmayer, S. J., Bergemann, C. M., King, D. E., Morton, K. S., Romersi, R. F., Jameson, L. E., Leung, M. C. K., Andersen, E. C., Taubert, S., et al. (2021) · Journal of Toxicology and Environmental Health Part B · doi:10.1080/10937404.2021.1884921 · Cited by 124 · see citing works
Salminen, A., Ojala, J. O., Huuskonen, J., Kauppinen, A., Suuronen, T., & Kaarniranta, K. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-7461-3 · Cited by 119 · see citing works
Integrating evolutionary and molecular genetics of aging
Flatt, T., & SCHMIDT, P. S. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.07.010 · Cited by 116 · see citing works
Ghazi, A., Henis‐Korenblit, S., & Kenyon, C. J. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000639 · Cited by 108 · see citing works
Przybysz, A. J., Choe, K. P., Roberts, L. J., & Strange, K. B. (2009) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2009.02.004 · Cited by 108 · see citing works
MicroRNA in Aging: From Discovery to Biology
Jung, H. J., & Suh, Y. (2012) · Current Genomics · doi:10.2174/138920212803251436 · Cited by 106 · see citing works
Quercetin-mediated longevity in Caenorhabditis elegans: Is DAF-16 involved?
Saul, N., Pietsch, K., Menzel, R., & Steinberg, C. E. W. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.07.001 · Cited by 106 · see citing works
Bonomo, L., Silva, D. N., Boasquívis, P. F., Paiva, F. A., Guerra, J. F. D. C., Martins, T. A. F., Torres, Á. G. D. J., de Paula, I. T. B. R., Caneschi, W. L., Jacolot, P., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089933 · Cited by 95 · see citing works
Barger, J. L., Kayo, T., Pugh, T. D., Prolla, T. A., & Weindruch, R. H. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2008.06.013 · Cited by 89 · see citing works
Hartwig, K., Heidler, T., Moch, J., Daniel, H., & Wenzel, U. (2009) · Genes & Nutrition · doi:10.1007/s12263-009-0113-x · Cited by 89 · see citing works
DAF-16 target identification in C. elegans: past, present and future
Tullet, J. M. A. (2014) · Biogerontology · doi:10.1007/s10522-014-9527-y · Cited by 87 · see citing works
Zhang, B., Cui, S., Bai, X., Zhuo, L., Sun, X., Hong, Q., Fu, B., Wang, J., Chen, X., & Cai, G. (2013) · AGE · doi:10.1007/s11357-013-9520-4 · Cited by 88 · see citing works
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 · see citing works
Tian, J., Geiss, C., Zarse, K., Madreiter‐Sokolowski, C. T., & Ristow, M. (2021) · Aging · doi:10.18632/aging.203597 · Cited by 78 · see citing works
Ávila, D. S., Benedetto, A., Au, C., Manarin, F., Erikson, K. M., Soares, F. A. A., da Rocha, J. B. T., & Aschner, M. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.02.044 · Cited by 76 · see citing works
Amrit, F. R. G., Steenkiste, E. M., Ratnappan, R., Chen, S.-W., McClendon, T. B., Kostka, D., Yanowitz, J. L., Olsen, C. P., & Ghazi, A. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005788 · Cited by 78 · see citing works
Li, L.-B., Lei, H., Arey, R. N., Li, P., Liu, J., Murphy, C. T., Xu, X. Z. S., & Shen, K. (2016) · Current Biology · doi:10.1016/j.cub.2015.12.068 · Cited by 74 · see citing works
Self-citationTranscription Regulation by Class III Histone Deacetylases (HDACs)—Sirtuins
Dai, Y. (2008) · Translational Oncogenomics · doi:10.4137/tog.s483 · Cited by 74 · see citing works
Minniti, A. N., Cataldo, R., Trigo, C., Vásquez, L., Mujica, P. E., Leighton, F., Inestrosa, N. C., & Aldunate, R. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00521.x · Cited by 73 · see citing works
Deregulation of FOXO3A during prostate cancer progression
Gupta (2009) · International Journal of Oncology · doi:10.3892/ijo_00000291 · Cited by 68 · see citing works
Depuydt, G., Xie, F., Petyuk, V., Smolders, A., Brewer, H. M., Camp, D., Smith, R. D., & Braeckman, B. P. (2014) · Journal of Proteome Research · doi:10.1021/pr401081b · Cited by 64 · see citing works
Fatty-acid metabolism is involved in stress-resistance mechanisms of Caenorhabditis elegans
Horikawa, M., & Sakamoto, K. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.11.006 · Cited by 64 · see citing works
Genetic and molecular analysis of nematode–microbe interactions
Tan, M.-W., & Shapira, M. (2011) · Cellular Microbiology · doi:10.1111/j.1462-5822.2011.01570.x · Cited by 52 · see citing works
Oxidation and Antioxidation of Natural Products in the Model Organism Caenorhabditis elegans
Zhu, A., Zheng, F., Zhang, W., Li, L., Li, Y., Hu, H., Wu, Y., Bao, W., Li, G., Wang, Q., et al. (2022) · Antioxidants · doi:10.3390/antiox11040705 · Cited by 64 · see citing works
Caffeic acid protects against Aβ toxicity and prolongs lifespan in Caenorhabditis elegans models
Li, H., Yu, X., Li, C., Ma, L., Zhao, Z., Guan, S., & Wang, L. (2021) · Food & Function · doi:10.1039/d0fo02784g · Cited by 60 · see citing works
Yamamoto, R., & Tatar, M. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00716.x · Cited by 60 · see citing works
A Long Noncoding RNA on the Ribosome Is Required for Lifespan Extension
Essers, P., Nonnekens, J., Goos, Y. J., Betist, M. C., Viester, M. D. M., Mossink, B., Lansu, N. R., Korswagen, H. C., Jelier, R., Brenkman, A. B., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2014.12.029 · Cited by 59 · see citing works
Garcia, A. M., Ladage, M. L., Dumesnil, D. R., Zaman, K., Shulaev, V., Azad, R. K., & Padilla, P. A. (2015) · Genetics · doi:10.1534/genetics.115.174631 · Cited by 59 · see citing works
Keowkase, R., Aboukhatwa, M. A., & Luo, Y. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.04.008 · Cited by 58 · see citing works
Wu, N., Zheng, W., Zhou, Y., Tian, Y., Tang, M., Feng, X., Ashrafizadeh, M., Wang, Y. Z., Niu, X., Tambuwala, M. M., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102428 · Cited by 56 · see citing works
Tseng, H.-L., Li, C., Huang, L.-H., Chen, C., Tsai, C., Lin, C., & Hsu, H. (2012) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2012.07.022 · Cited by 56 · see citing works
Cong, W., Wang, P., Qu, Y., Tang, J., Bai, R., Zhao, Y., Chen, C., & Bi, X. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.11.048 · Cited by 56 · see citing works
Anti-aging effects of deuterium depletion on Mn-induced toxicity in a C. elegans model
Ávila, D. S., Somlyai, G., Somlyai, I., & Aschner, M. (2012) · Toxicology Letters · doi:10.1016/j.toxlet.2012.04.014 · Cited by 56 · see citing works
Mehdi, M. M., Solanki, P., & Singh, P. (2021) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2021.104413 · Cited by 54 · see citing works
Fleckenstein, T., Kastenmüller, A., Stein, M., Peters, C., Daake, M., Krause, M., Weinfurtner, D., Haslbeck, M., Weinkauf, S., Groll, M., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.04.019 · Cited by 54 · see citing works
Baxi, K., Ghavidel, A., Waddell, B. M., Harkness, T. A. A., & de Carvalho, C. E. (2017) · Genetics · doi:10.1534/genetics.117.204222 · Cited by 53 · see citing works
Mertenskötter, A., Keshet, A., Gerke, P., & Paul, R. J. (2012) · Cell Stress and Chaperones · doi:10.1007/s12192-012-0382-y · Cited by 53 · see citing works
Opposing roles of microRNA Argonautes during Caenorhabditis elegans aging
Aalto, A. P., Nicastro, I. A., Broughton, J. P., Chipman, L. B., Schreiner, W. P., Chen, J. S., & Pasquinelli, A. E. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007379 · Cited by 52 · see citing works
ETS-4 Is a Transcriptional Regulator of Life Span in Caenorhabditis elegans
Thyagarajan, B., Blaszczak, A. G., Chandler, K. J., Watts, J. L., Johnson, W. E., & Graves, B. J. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001125 · Cited by 51 · see citing works
Han, S. M., Oussini, H. E., Scekic‐Zahirovic, J., Vibbert, J., Cottee, P. A., PRASAIN, J. K., Bellen, H. J., Dupuis, L., & Miller, M. A. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003738 · Cited by 49 · see citing works
de Candia, P., Blekhman, R., Chabot, A. E., Oshlack, A., & Gilad, Y. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001670 · Cited by 50 · see citing works
Hu, M., Lok, J. B., Ranjit, N., Massey, H. C., Sternberg, P. W., & Gasser, R. B. (2009) · International Journal for Parasitology · doi:10.1016/j.ijpara.2009.09.005 · Cited by 50 · see citing works
Activation of MAPK and FoxO by Manganese (Mn) in Rat Neonatal Primary Astrocyte Cultures
Exil, V. J., Li, P., Yu, Y., Chakraborty, S., Caito, S. W., Wells, K. S., Karki, P., Lee, E.-S., & Aschner, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094753 · Cited by 50 · see citing works
Sethupathy, S., Vigneshwari, L., Valliammai, A., Balamurugan, K., & Pandian, S. K. (2017) · RSC Advances · doi:10.1039/c7ra02934a · Cited by 49 · see citing works
Mechanisms and Evolution of Environmental Responses in Caenorhabditis elegans
Braendle, C., Milloz, J., & Félix, M. (2007) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(07)80005-6 · Cited by 43 · see citing works
Kim, S.-H., Kim, B.-K., Park, S.-H., & Park, S.-K. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/2860642 · Cited by 46 · see citing works
Park, S.-H., & Park, S.-K. (2022) · Antioxidants · doi:10.3390/antiox11101996 · Cited by 45 · see citing works
Pinkas, A., & Aschner, M. (2016) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.6b00034 · Cited by 45 · see citing works
Toxicity of nonylphenol and nonylphenol ethoxylate on Caenorhabditis elegans
la Parra-Guerra, A. C. D., & Olivero‐Verbel, J. (2019) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2019.109709 · Cited by 44 · see citing works
Gimenez, L. E., Ghildyal, P., Fischer, K. E., Hu, H., Ja, W. W., Eaton, B. A., Wu, Y., Austad, S. N., & Ranjan, R. (2012) · Aging Cell · doi:10.1111/acel.12027 · Cited by 41 · see citing works
Warnhoff, K., Murphy, J. T., Kumar, S., Schneider, D. L., Peterson, M., Hsu, S., Guthrie, J. M., Robertson, J. D., & Kornfeld, K. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004703 · Cited by 42 · see citing works
Phenotypic Covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes
Amrit, F. R. G., Boehnisch, C., & May, R. C. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009978 · Cited by 40 · see citing works
Kronberg, F., Clavijo, A., Moya, A., Rossen, A., Calvo, D., Pagano, E. A., & Munarriz, E. R. (2018) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2018.08.002 · Cited by 41 · see citing works
Park, S.-H., Kim, B.-K., & Park, S.-K. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111498 · Cited by 40 · see citing works
FoxO induces pupal diapause by decreasing TGFβ signaling
Zhang, X.-S., Wang, Z.-H., Li, W., & Xu, W. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2210404119 · Cited by 39 · see citing works
Horikawa, M., & Sakamoto, K. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.03.004 · Cited by 38 · see citing works
Nonautonomous Regulation of Neuronal Migration by Insulin Signaling, DAF-16/FOXO, and PAK-1
Kennedy, L. M., Pham, S. C. D. L., & Grishok, A. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.07.045 · Cited by 37 · see citing works
Yu, C., How, C. M., & Liao, V. H. (2016) · Chemosphere · doi:10.1016/j.chemosphere.2016.01.004 · Cited by 36 · see citing works
Selenite protects C aenorhabditis elegans from oxidative stress via DAF ‐16 and TRXR ‐1
Li, W.-H., Shi, Y., Chang, C., Huang, C., & Liao, V. H. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201300404 · Cited by 34 · see citing works
Genetics and Pharmacology of Longevity
Castillo-Quan, J. I., Kinghorn, K. J., & Bjedov, I. (2015) · Advances in genetics · doi:10.1016/bs.adgen.2015.06.002 · Cited by 37 · see citing works
Ayyadevara, S., Tazearslan, Ç., Bharill, P., Alla, R., Siegel, E. R., & Reis, R. J. S. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00524.x · Cited by 33 · see citing works
Ubiquitylation Pathways In Insulin Signaling and Organismal Homeostasis
Balaji, V., Pokrzywa, W., & Hoppe, T. (2018) · BioEssays · doi:10.1002/bies.201700223 · Cited by 33 · see citing works
Keshet, A., Mertenskötter, A., Winter, S. A., Brinkmann, V., Dölling, R., & Paul, R. J. (2017) · Molecular Genetics and Genomics · doi:10.1007/s00438-017-1351-z · Cited by 32 · see citing works
Genetics of frailty: A longevity perspective
Sathyan, S., & Verghese, J. (2020) · Translational research · doi:10.1016/j.trsl.2020.03.005 · Cited by 30 · see citing works
Nutrition and microRNAs: Novel Insights to Fight Sarcopenia
Barbiera, A., Pelosi, L., Sica, G., & Scicchitano, B. M. (2020) · Antioxidants · doi:10.3390/antiox9100951 · Cited by 32 · see citing works
Li, R., Tao, M., Wu, T., Zhang, Z., Xu, T., Pan, S., & Xu, X. (2021) · Food & Function · doi:10.1039/d1fo01383a · Cited by 31 · see citing works
Transcriptional networks that mediate signals from reproductive tissues to influence lifespan
Ghazi, A. (2012) · genesis · doi:10.1002/dvg.22345 · Cited by 30 · see citing works
C. elegans insulin-like peptides
Zhu, R., & Chin-Sang, I. D. (2024) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2024.112173 · Cited by 29 · see citing works
Jiménez‐Hidalgo, M., Kurz, C. L., Pedrajas, J. R., Naranjo-Galindo, F. J., González-Barrios, M., Cabello, J., Sáez, A. G., Lozano, E., Button, E. L., Veal, E. A., et al. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.11.023 · Cited by 30 · see citing works
Devagi, G., Mohankumar, A., Shanmugam, G., Nivitha, S., Dallemer, F., Kalaivani, P., Sundararaj, P., & Prabhakaran, R. (2018) · Scientific Reports · doi:10.1038/s41598-018-25984-7 · Cited by 29 · see citing works
Discovery of Functional Gene Variants Associated With Human Longevity: Opportunities and Challenges
Tazearslan, C., Cho, M., & Suh, Y. (2011) · The Journals of Gerontology Series A · doi:10.1093/gerona/glr200 · Cited by 29 · see citing works
Tazearslan, Ç., Ayyadevara, S., Bharill, P., & Reis, R. J. S. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000452 · Cited by 27 · see citing works
Marfil-Sánchez, A., Zhang, L., Alonso-Pernas, P., Mirhakkak, M. H., Mueller, M., Seelbinder, B., Ni, Y., Santhanam, R., Busch, A., Beemelmanns, C., et al. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1993598 · Cited by 28 · see citing works
Deficiency of metallothionein-1 and -2 genes shortens the lifespan of the 129/Sv mouse strain
Kadota, Y., Aki, Y., Toriuchi, Y., Mizuno, Y., Kawakami, T., Sato, M., & Suzuki, S. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.04.007 · Cited by 24 · see citing works
Huang, C., Hsu, F.-Y., Wu, Y.-H., Zhong, L., Tseng, M.-Y., Kuo, C.-J., Hsu, A., Liang, S., & Chiou, S. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.02.010 · Cited by 24 · see citing works
Néri, C. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00015 · Cited by 23 · see citing works
A genome-wide screen of bacterial mutants that enhance dauer formation in C. elegans
Khanna, A., Kumar, J., Vargas, M. A., Barrett, L., Katewa, S. D., Li, P. W. F., McCloskey, T., Sharma, A., Naudé, N., Nelson, C. S., et al. (2016) · Scientific Reports · doi:10.1038/srep38764 · Cited by 23 · see citing works
- Authors
- Murphy, C. T.
- Affiliations
- Princeton University (US)
- Corresponding author
- Murphy, Coleen T.
- ORCID
- Murphy, Coleen T.
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2006-10
- Volume
- 41
- Issue
- 10
- Pages
- 910-921
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W1966040173
- Cited by
- 189
- References
- 70
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 9 · 2023: 3 · 2022: 10 · 2021: 12 · 2020: 6 · 2019: 9 · 2018: 8 · 2017: 7 · 2016: 10 · 2015: 10 · 2014: 16 · 2013: 13 · 2012: 20
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- DAF-16, FOXO transcription factors, transcription factor target genes, lifespan extension, longevity, Caenorhabditis elegans, dauer formation, fat deposition, stress protection, gene expression regulation
- MeSH terms
- Aging, Animals, Insulin, Longevity, Models, Genetic, Receptor, Insulin, Transcription Factors, Transcription, Genetic, Signal Transduction, Caenorhabditis elegans, Genes, Helminth, Receptor, IGF Type 2, Gene Expression Regulation, Developmental, Caenorhabditis elegans Proteins, 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