Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF‐16
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Summary: In Caenorhabditis elegans, the forkhead protein DAF‐16 transduces insulin‐like signals that regulate larval development and adult lifespan. To identify DAF‐16‐dependent transcriptional alterations that occur in a long‐lived C. elegans strain, we used cDNA microarrays and genomic analysis to identify putative direct and indirect DAF‐16 transcriptional target genes. Our analysis suggests that DAF‐16 action regulates a wide range of physiological responses by altering the expression of genes involved in metabolism, energy generation and cellular stress responses. Furthermore, we observed a large overlap between DAF‐16‐dependent transcription and genes normally expressed in the long‐lived dauer larval stage. Finally, we examined the in vivo role of 35 of these target genes by RNA‐mediated interference and identified one gene encoding a putative protease that is necessary for the daf‐2 Age phenotype.
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SOD-1 and SOD-2 are transcriptionally regulated by DAF-16.
“consistent with their DAF-16-dependent transcriptional regulation (McElwee et al., 2003; Murphy et al., 2003).”
From Widespread Proteome Remodeling and Aggregation in Aging C. elegans (2015) · cites this paper as McElwee et al., 2003
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1 retracted
A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants
Taub, J. J., Lau, J. F., Ma, C., Hahn, J. H., Hoque, R., Rothblatt, J. A., & Chalfie, M. (1999) · Nature · doi:10.1038/20208 · Cited by 243 · see citing works
RetractedPotent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., & Mello, C. C. (1998) · Nature · doi:10.1038/35888 · Cited by 15,429 · see citing works
Oxidants, oxidative stress and the biology of ageing
Finkel, T., & Holbrook, N. J. (2000) · Nature · doi:10.1038/35041687 · Cited by 9,413 · 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
Kimura, K. D., Tissenbaum, H. A., Liu, Y., & Ruvkun, G. (1997) · Science · doi:10.1126/science.277.5328.942 · Cited by 2,250 · see citing works
Ogg, 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
Timmons, L., Court, D. L., & Fire, A. Z. (2001) · Gene · doi:10.1016/s0378-1119(00)00579-5 · Cited by 1,852 · see citing works
Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress
Kops, G. J. P. L., Dansen, T. B., Polderman, P. E., Saarloos, I., Wirtz, K. W. A., Coffer, P. J., Huang, T.-T., Bos, J. L., Medema, R. H., & Burgering, B. M. T. (2002) · Nature · doi:10.1038/nature01036 · Cited by 1,580 · see citing works
Lin, K., Dorman, J. B., Rodan, A. R., & Kenyon, C. J. (1997) · Science · doi:10.1126/science.278.5341.1319 · Cited by 1,496 · see citing works
AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1
Medema, R. H., Kops, G. J. P. L., Bos, J. L., & Burgering, B. M. T. (2000) · Nature · doi:10.1038/35008115 · Cited by 1,439 · see citing works
Kamath, R. S., Martinez-Campos, M., Zipperlen, P., Fraser, A. G., & Ahringer, J. (2000) · Genome biology · doi:10.1186/gb-2000-2-1-research0002 · Cited by 1,315 · see citing works
The genetics of caloric restriction in Caenorhabditis elegans
Lakowski, B., & Hekimi, S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.22.13091 · Cited by 967 · 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
The dauerlarva, a post-embryonic developmental variant of the nematode Caenorhabditis elegans
Cassada, R. C., & Russell, R. L. (1975) · Developmental Biology · doi:10.1016/0012-1606(75)90109-8 · Cited by 901 · see citing works
DNA Repair Pathway Stimulated by the Forkhead Transcription Factor FOXO3a Through the Gadd45 Protein
Tran, H. G., Brunet, A., Grenier, J. M., Datta, S. R., Fornace, A. J., DiStefano, P. S., Chiang, L. W., & Greenberg, M. E. (2002) · Science · doi:10.1126/science.1068712 · Cited by 860 · see citing works
Redox Regulation of Forkhead Proteins Through a <i>p66shc</i> -Dependent Signaling Pathway
Nemoto, S., & Finkel, T. (2002) · Science · doi:10.1126/science.1069004 · Cited by 818 · see citing works
Honda, Y., & Honda, S. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.11.1385 · Cited by 730 · see citing works
Gems, D., Sutton, A. J., Sundermeyer, M. L., Albert, P. S., King, K. V., Edgley, M. L., Larsen, P. L., & Riddle, D. L. (1998) · Genetics · doi:10.1093/genetics/150.1.129 · Cited by 718 · see citing works
Paradis, S., & Ruvkun, G. (1998) · Genes & Development · doi:10.1101/gad.12.16.2488 · Cited by 711 · see citing works
Mitochondrial Electron Transport Is a Key Determinant of Life Span in Caenorhabditis elegans
Feng, J., Bussière, F., & Hekimi, S. (2001) · Developmental Cell · doi:10.1016/s1534-5807(01)00071-5 · Cited by 675 · 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
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
Yu, B., Masoro, E. J., & McMahan, C. A. (1985) · Journal of Gerontology · doi:10.1093/geronj/40.6.657 · Cited by 591 · see citing works
A Global Profile of Germline Gene Expression in C. elegans
Reinke, V., Smith, H. E., Nance, J., Wang, J., Doren, C. V., Begley, R., Jones, S. J. M., Davis, E. B., Scherer, S., Ward, S. F., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00059-9 · Cited by 578 · see citing works
Genome-Wide Transcript Profiles in Aging and Calorically Restricted Drosophila melanogaster
Pletcher, S. D., Macdonald, S. J., Marguerie, R., Certa, U., Stearns, S. C., Goldstein, D. B., & Partridge, L. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00808-4 · Cited by 568 · see citing works
Statistical design and the analysis of gene expression microarray data
Kerr, K. F., & Churchill, G. A. (2007) · Genetics Research · doi:10.1017/s0016672308009713 · Cited by 561 · see citing works
Lee, R., Hench, J., & Ruvkun, G. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00595-4 · Cited by 508 · see citing works
Furuyama, T., Nakazawa, T., Nakano, I., et al. (2000) · Biochemical Journal · doi:10.1042/bj3490629 · Cited by 505 · see citing works
Statistical design and the analysis of gene expression microarray data
Kerr, K. F., & Churchill, G. A. (2001) · Genetics Research · doi:10.1017/s0016672301005055 · Cited by 501 · see citing works
Dorman, J. B., Albinder, B., Shroyer, T., & Kenyon, C. J. (1995) · Genetics · doi:10.1093/genetics/141.4.1399 · Cited by 449 · see citing works
Chapman, T., & Partridge, L. (1996) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1996.0113 · Cited by 436 · see citing works
Paradis, S., Ailion, M., Toker, A., Thomas, J. H., & Ruvkun, G. (1999) · Genes & Development · doi:10.1101/gad.13.11.1438 · Cited by 428 · see citing works
Self-citationGottlieb, S., & Ruvkun, G. (1994) · Genetics · doi:10.1093/genetics/137.1.107 · Cited by 387 · see citing works
Oxidative stress and ageing in Caenorhabditis elegans
Vanfleteren, J. R. (1993) · Biochemical Journal · doi:10.1042/bj2920605 · Cited by 383 · see citing works
An intervention resembling caloric restriction prolongs life span and retards aging in yeast
Jiang, J. C., Jaruga, E., Repnevskaya, M. V., & Jazwinski, S. M. (2000) · The FASEB Journal · doi:10.1096/fj.00-0242fje · Cited by 383 · see citing works
Non-ageing developmental variant of Caenorhabditis elegans
Klass, M. R., & Hirsh, D. (1976) · Nature · doi:10.1038/260523a0 · Cited by 380 · see citing works
Characterization of a germ-line proliferation mutation in C. elegans
Beanan, M. J., & Strome, S. (1992) · Development · doi:10.1242/dev.116.3.755 · Cited by 312 · see citing works
Transcriptional Profile of Aging in C. elegans
Lund, J., Tedesco, P. M., Duke, K., Wang, J., Kim, S. K., & Johnson, T. E. (2002) · Current Biology · doi:10.1016/s0960-9822(02)01146-6 · Cited by 304 · see citing works
Costanzo, M. C. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.73 · Cited by 288 · see citing works
Jiang, M., Ryu, J., Kiraly, M., Duke, K., Reinke, V., & Kim, S. K. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.218 · Cited by 285 · see citing works
Mutants with altered muscle structure in Caenorhabditis elegans
Waterston, R., Thomson, J. N., & Brenner, S. (1980) · Developmental Biology · doi:10.1016/0012-1606(80)90475-3 · Cited by 271 · see citing works
DNA Damage as the Primary Cause of Aging
Gensler, H. L., & Bernstein, H. (1981) · The Quarterly Review of Biology · doi:10.1086/412317 · Cited by 252 · see citing works
LeRoith, D. (2002) · The American Journal of Medicine · doi:10.1016/s0002-9343(02)01276-7 · Cited by 235 · see citing works
Jones, S. J. M., Riddle, D. L., Pouzyrev, A. T., Velculescu, V. E., Hillier, L., Eddy, S. R., Stricklin, S. L., Baillie, D. L., Waterston, R., & Marra, M. A. (2001) · Genome Research · doi:10.1101/gr.184401 · Cited by 227 · see citing works
HEAT SHOCK RESPONSE AND AGEING: MECHANISMS AND APPLICATIONS
Verbeke, P., Fonager, J., Clark, B. F. C., & Rattan, S. I. S. (2001) · Cell Biology International · doi:10.1006/cbir.2001.0789 · Cited by 220 · see citing works
Apoptosis in the aging process
Higami, Y., & Shimokawa, I. (2000) · Cell and Tissue Research · doi:10.1007/s004419900156 · Cited by 213 · see citing works
Protein Degradation by the Proteasome and Its Implications in Aging
Friguet, B., Bulteau, A., Chondrogianni, N., Conconi, M., & Petropoulos, I. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06643.x · Cited by 172 · see citing works
The gerontogenes age‐1 and daf‐2 determine metabolic rate potential in aging Caenorhabditis elegans
Vanfleteren, J. R., & Vreese, A. D. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.13.7557026 · Cited by 160 · see citing works
Tsang, W. Y., Sayles, L. C., Grad, L. I., Pilgrim, D. B., & Lemire, B. D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103999200 · Cited by 148 · see citing works
Hunter, T., BANNISTER, W. H., & Hunter, G. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.45.28652 · Cited by 142 · see citing works
Neurosecretory control of aging in <i>Caenorhabditis</i> <i>elegans</i>
Ailion, M., Inoue, T., Weaver, C. I., Holdcraft, R. W., & Thomas, J. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.13.7394 · Cited by 121 · see citing works
Self-citationJohnson, T. E., Cypser, J. R., de Castro, E., Castro, S., Henderson, S. T., Murakami, S., Rikke, B. A., Tedesco, P., & Link, C. D. (2000) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00138-8 · Cited by 115 · see citing works
Insulin-like signaling, metabolism, stress resistance and aging in Caenorhabditis elegans
Braeckman, B. P. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00222-6 · Cited by 110 · see citing works
Dalley, B. K., & Golomb, M. (1992) · Developmental Biology · doi:10.1016/0012-1606(92)90215-3 · Cited by 96 · see citing works
O'Riordan, V. B., & Burnell, A. M. (1989) · Comparative Biochemistry and Physiology Part B Comparative Biochemistry · doi:10.1016/0305-0491(89)90271-x · Cited by 96 · see citing works
O'Riordan, V. B., & Burnell, A. M. (1990) · Comparative Biochemistry and Physiology Part B Comparative Biochemistry · doi:10.1016/0305-0491(90)90258-u · Cited by 84 · see citing works
Murakami, S., & Johnson, T. E. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00453-5 · Cited by 82 · see citing works
Calorie Restriction and Age‐Related Oxidative Stress
Merry, B. J. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06646.x · Cited by 68 · 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
Hekimi, S., Burgess, J., Bussière, F., Meng, Y., & Bénard, C. Y. (2001) · Trends in Genetics · doi:10.1016/s0168-9525(01)02523-9 · Cited by 67 · see citing works
Modulation of Gene Expression in Autoimmune Disease and Aging by Food Restriction and Dietary Lipids
Fernandes, G., Venkatraman, J. T., Khare, A., Horbach, G. J., & Friedrichs, W. E. (1990) · Experimental Biology and Medicine · doi:10.3181/00379727-193-42983 · Cited by 47 · see citing works
The mitochondrial theory of aging:
Gershon, D. (1999) · Experimental Gerontology · doi:10.1016/s0531-5565(99)00010-8 · Cited by 26 · see citing works
Drnková, J., Nováková, O., & Kubišta, V. (1990) · Comparative Biochemistry and Physiology Part C Comparative Pharmacology · doi:10.1016/0742-8413(90)90093-o · Cited by 2 · see citing works
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- Authors
- McElwee, J., Bubb, K., & Thomas, J. H.
- Affiliations
- University of Washington (US)
- Corresponding author
- Thomas, James H.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2003-03-26
- Volume
- 2
- Issue
- 2
- Pages
- 111-121
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W2013388821
- Cited by
- 416
- References
- 64
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 7 · 2023: 5 · 2022: 12 · 2021: 11 · 2020: 8 · 2019: 11 · 2018: 9 · 2017: 14 · 2016: 18 · 2015: 23 · 2014: 23 · 2013: 19 · 2012: 19
- FWCI
- 7.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (T32AG000057)
- 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 › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Keywords
- DAF-16, forkhead transcription factor, Caenorhabditis elegans, insulin-like signaling, transcription factor target genes, longevity, energy metabolism, cellular stress response, daf-2, proteolytic enzymes, RNA interference
- MeSH terms
- Animals, Larva, Longevity, Phenotype, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, RNA, Messenger, Transcription Factors, Transcription, Genetic, Caenorhabditis elegans, Gene Expression Regulation, Developmental, DNA, Helminth, RNA, Helminth, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Caenorhabditis elegans Proteins, RNA Interference, Forkhead Transcription Factors
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