Cited by 820Genetics, Aging, and Longevity in Model OrganismsMetabolism, Diabetes, and CancerNeurobiology and Insect Physiology Research

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Tissue-Specific Activities of C. elegans DAF-16 in the Regulation of Lifespan

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Libina, Nataliya, Berman, Jennifer R., Kenyon, Cynthia·2003·Cell

DOI 10.1016/s0092-8674(03)00889-4

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Abstract

In C. elegans, the transcription factor DAF-16 promotes longevity in response to reduced insulin/IGF-1 signaling or germline ablation. In this study, we have asked how different tissues interact to specify the lifespan of the animal. We find that several tissues act as signaling centers. In particular, DAF-16 activity in the intestine, which is also the animal's adipose tissue, completely restores the longevity of daf-16(-) germline-deficient animals, and increases the lifespans of daf-16(-) insulin/IGF-1-pathway mutants substantially. Our findings indicate that DAF-16 may control two types of downstream signals: DAF-16 activity in signaling cells upregulates DAF-16 in specific responding tissues, possibly via regulation of insulin-like peptides, and also evokes DAF-16-independent responses. We suggest that this network of tissue interactions and feedback regulation allows the tissues to equilibrate and fine-tune their expression of downstream genes, which, in turn, coordinates their rates of aging within the animal.

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The embryonic cell lineage of the nematode Caenorhabditis elegans
Sulston, J. E., Schierenberg, E., White, J. G., & Thomson, J. N. (1983) · Developmental Biology · doi:10.1016/0012-1606(83)90201-4 · Cited by 4,199
Post-embryonic cell lineages of the nematode, Caenorhabditis elegans
Sulston, J. E., & Horvitz, H. R. (1977) · Developmental Biology · doi:10.1016/0012-1606(77)90158-0 · Cited by 3,479
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
Self-citation
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
Self-citation
daf-2 , an Insulin Receptor-Like Gene That Regulates Longevity and Diapause in Caenorhabditis elegans
Kimura, K. D., Tissenbaum, H. A., Liu, Y., & Ruvkun, G. (1997) · Science · doi:10.1126/science.277.5328.942 · Cited by 2,250
The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans
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
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 1,761
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
Self-citation
daf-16 : An HNF-3/forkhead Family Member That Can Function to Double the Life-Span of Caenorhabditis elegans
Lin, K., Dorman, J. B., Rodan, A. R., & Kenyon, C. J. (1997) · Science · doi:10.1126/science.278.5341.1319 · Cited by 1,501
Self-citation
Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans
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 1,332
The Endocrine Regulation of Aging by Insulin-like Signals
Tatar, M., Bartke, A., & Antebi, A. (2003) · Science · doi:10.1126/science.1081447 · Cited by 1,327
Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans
Herndon, L. A., Schmeissner, P. J., Dudaronek, J. M., Brown, P. A., Listner, K. M., Sakano, Y., Paupard, M. C., Hall, D. H., & Driscoll, M. (2002) · Nature · doi:10.1038/nature01135 · Cited by 1,214
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
Tissue-Specific Knockout of the Insulin Receptor in Pancreatic β Cells Creates an Insulin Secretory Defect Similar to that in Type 2 Diabetes
Kulkarni, R., Brüning, J. C., Winnay, J. N., Postic, C., Magnuson, M. A., & Kahn, C. R. (1999) · Cell · doi:10.1016/s0092-8674(00)80546-2 · Cited by 1,148
Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling
Lin, K., Hsin, H., Libina, N., & Kenyon, C. J. (2001) · Nature Genetics · doi:10.1038/88850 · Cited by 1,027
Self-citation
Signals from the reproductive system regulate the lifespan of C. elegans
Hsin, H., & Kenyon, C. J. (1999) · Nature · doi:10.1038/20694 · Cited by 1,014
Self-citation
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 990
daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans
Henderson, S. T., & Johnson, T. E. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00594-2 · Cited by 949
Chapter 19 DNA Transformation
Mello, C., & Fire, A. (1995) · Methods in cell biology · doi:10.1016/s0091-679x(08)61399-0 · Cited by 947
A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans
Morris, J. Z., Tissenbaum, H. A., & Ruvkun, G. (1996) · Nature · doi:10.1038/382536a0 · Cited by 891
Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress
Lithgow, G. J., White, T. M., Melov, S., & Johnson, T. E. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.16.7540 · Cited by 862
Genetic Analysis of Tissue Aging in Caenorhabditis elegans : A Role for Heat-Shock Factor and Bacterial Proliferation
Garigan, D., Hsu, A.-L., Fraser, A. G., Kamath, R. S., Ahringer, J., & Kenyon, C. (2002) · Genetics · doi:10.1093/genetics/161.3.1101 · Cited by 803
Self-citation
The daf‐2 gene network for longevity regulates oxidative stress resistance and Mn‐superoxide dismutase gene expression in Caenorhabditis elegans
Honda, Y., & Honda, S. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.11.1385 · Cited by 730
Aging and resistance to oxidative damage in Caenorhabditis elegans.
Larsen, P. L. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.19.8905 · Cited by 722
Two Pleiotropic Classes of daf-2 Mutation Affect Larval Arrest, Adult Behavior, Reproduction and Longevity in Caenorhabditis elegans
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
Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factorPreprint
Paradis, S., & Ruvkun, G. (1998) · Genes & Development · doi:10.1101/gad.12.16.2488 · Cited by 710
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
Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologues
Furuyama, T., Nakazawa, T., Nakano, I., & Mori, N. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3490629 · Cited by 672
DAF-16 Target Genes That Control C. elegans Life-Span and Metabolism
Lee, S. S., Kennedy, S., Tolonen, A. C., & Ruvkun, G. (2003) · Science · doi:10.1126/science.1083614 · Cited by 669
Regulation of DAF-2 receptor signaling by human insulin and ins-1 , a member of the unusually large and diverse C. elegans insulin gene familyPreprint
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 651
The Caenorhabditis elegans dauer larva: Developmental effects of pheromone, food, and temperature
Golden, J. W., & Riddle, D. L. (1984) · Developmental Biology · doi:10.1016/0012-1606(84)90201-x · Cited by 602
Genes that regulate both development and longevity in Caenorhabditis elegans.
Larsen, P. L., Albert, P. S., & Riddle, D. L. (1995) · Genetics · doi:10.1093/genetics/139.4.1567 · Cited by 584
Regulation of Life-Span by Germ-Line Stem Cells in Caenorhabditis elegans
Arantes-Oliveira, N., Apfeld, J., Dillin, A. G., & Kenyon, C. J. (2002) · Science · doi:10.1126/science.1065768 · Cited by 530
Self-citation
Interacting genes in nematode dauer larva formation
Riddle, D. L., Swanson, M. M., & Albert, P. S. (1981) · Nature · doi:10.1038/290668a0 · Cited by 518
Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologues
Furuyama, T., Nakazawa, T., Nakano, I., et al. (2000) · Biochemical Journal · doi:10.1042/bj3490629 · Cited by 505
Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway
Lee, R., Hench, J., & Ruvkun, G. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00595-4 · Cited by 499
Genetic 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
Timing Requirements for Insulin/IGF-1 Signaling in C. elegans
Dillin, A., Crawford, D. K., & Kenyon, C. (2002) · Science · doi:10.1126/science.1074240 · Cited by 443
Self-citation
Identification and cloning of unc-119, a gene expressed in the Caenorhabditis elegans nervous system.
Maduro, M., & Pilgrim, D. B. (1995) · Genetics · doi:10.1093/genetics/141.3.977 · Cited by 437
A Pheromone Influences Larval Development in the Nematode Caenorhabditis elegans
Golden, J. W., & Riddle, D. L. (1982) · Science · doi:10.1126/science.6896933 · Cited by 429
Transcriptional outputs of the Caenorhabditis elegans 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
daf-2, daf-16 and daf-23: genetically interacting genes controlling Dauer formation in Caenorhabditis elegans.
Gottlieb, S., & Ruvkun, G. (1994) · Genetics · doi:10.1093/genetics/137.1.107 · Cited by 387
Oxidative stress and ageing in Caenorhabditis elegans
Vanfleteren, J. R. (1993) · Biochemical Journal · doi:10.1042/bj2920605 · Cited by 383
Cell Nonautonomy of C. elegans daf-2 Function in the Regulation of Diapause and Life Span
Apfeld, J., & Kenyon, C. J. (1998) · Cell · doi:10.1016/s0092-8674(00)81751-1 · Cited by 379
Self-citation
daf-28 encodes a C. elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathwayPreprint
Li, W., Kennedy, S. G., & Ruvkun, G. (2003) · Genes & Development · doi:10.1101/gad.1066503 · Cited by 376
Genetic analysis of chemosensory control of dauer formation in Caenorhabditis elegans.
Vowels, J. J., & Thomas, J. H. (1992) · Genetics · doi:10.1093/genetics/130.1.105 · Cited by 354
Thermotolerance of a Long-lived Mutant of Caenorhabditis elegans
Lithgow, G. J., White, T. M., Hinerfeld, D. A., & Johnson, T. E. (1994) · Journal of Gerontology · doi:10.1093/geronj/49.6.b270 · Cited by 213
Regulation of theXmyf-5andXmyoDExpression Pattern during Early Xenopus Development
Takahashi, S., Esumi, E., Nabeshima, Y., & Asashima, M. (1998) · ZOOLOGICAL SCIENCE · doi:10.2108/zsj.15.231 · Cited by 205
Molecular Cloning and Characterization of a New Insulin/IGF-like Peptide of the Nematode Caenorhabditis elegans
Kawano, T., Ito, Y., Ishiguro, M., Takuwa, K., Nakajima, T., & Kimura, Y. N. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2971 · Cited by 128
The ncl-1 gene and genetic mosaics of Caenorhabditis elegans.
Hedgecock, E. M., & Herman, R. K. (1995) · Genetics · doi:10.1093/genetics/141.3.989 · Cited by 110
Spatial Control of Gut-Specific Gene Expression During Caenorhabditis elegans Development
Aamodt, E. J., Chung, M. A., & McGhee, J. D. (1991) · Science · doi:10.1126/science.2020855 · Cited by 93
UNC-115, a Conserved Protein with Predicted LIM and Actin-Binding Domains, Mediates Axon Guidance in C. elegans
Lundquist, E. A., Herman, R. K., Shaw, J. E., & Bargmann, C. I. (1998) · Neuron · doi:10.1016/s0896-6273(00)80547-4 · Cited by 91
ANALYSIS OF GENETIC MOSAICS OF THE NEMATODE CAENORHABDITIS ELEGANS
Herman, R. K. (1984) · Genetics · doi:10.1093/genetics/108.1.165 · Cited by 90
The OLD-1 positive regulator of longevity and stress resistance is under DAF-16 regulation in Caenorhabditis elegans
Murakami, S., & Johnson, T. E. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00453-5 · Cited by 82
Identification of a DAF-16 Transcriptional Target Gene, scl-1, that Regulates Longevity and Stress Resistance in Caenorhabditis elegans
Ookuma, S., Fukuda, M., & Nishida, E. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00108-8 · Cited by 82
The Caenorhabditis elegans gene lin-26 is required to specify the fates of hypodermal cells and encodes a presumptive zinc-finger transcription factor
Labouesse, M., Sookhareea, S., & Horvitz, H. R. (1994) · Development · doi:10.1242/dev.120.9.2359 · Cited by 77
DAF-16-dependent and independent expression targets of DAF-2 insulin receptor-like pathway in Caenorhabditis elegans include FKBPs
Yu, H. M., & Larsen, P. L. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.5210 · Cited by 67
A tissue-specific knock-out strategy reveals that lin-26 is required for the formation of the somatic gonad epithelium in Caenorhabditis elegans
den Boer, B. G. W., Sookhareea, S., Dufourcq, P., & Labouesse, M. (1998) · Development · doi:10.1242/dev.125.16.3213 · Cited by 23
Studies of aging and diapause in C. elegans
Apfeld, J. (1999) · eScholarship (California Digital Library) · Cited by 1

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Authors: Libina, N., Berman, J. R., & Kenyon, C.
Affiliations: University of California, San Francisco (US)
Corresponding author: Kenyon, Cynthia
ORCID: Kenyon, Cynthia
Venue: Cell
Publisher: Elsevier BV
Published: 2003-11
Volume: 115
Issue: 4
Pages: 489-502
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/s0092-8674(03)00889-4
OpenAlex: W2066660409
Cited by: 820
References: 58
Citations by year: 2026: 19 · 2025: 32 · 2024: 41 · 2023: 15 · 2022: 35 · 2021: 53 · 2020: 39 · 2019: 35 · 2018: 48 · 2017: 36 · 2016: 42 · 2015: 24 · 2014: 44 · 2013: 40 · 2012: 33
FWCI: 9.40
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3546 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (AG11816)
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 › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
Keywords: DAF-16, Caenorhabditis elegans, lifespan regulation, insulin/IGF-1 signaling, intestine, adipose tissue, tissue-specific gene regulation, insulin-like peptides, aging, transcription factors
MeSH terms: Adipose Tissue, Aging, Animals, Insulin, Insulin-Like Growth Factor I, Intestinal Mucosa, Longevity, Mosaicism, Organ Specificity, Receptor, Insulin, RNA, Messenger, Stress, Physiological, Transcription Factors, Signal Transduction, Caenorhabditis elegans, Gene Deletion, Germ-Line Mutation, Gene Expression Regulation, Developmental, Gene Expression Profiling, Caenorhabditis elegans Proteins, Animals, Genetically Modified, Forkhead Transcription Factors

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Tissue-Specific Activities of C. elegans DAF-16 in the Regulation of Lifespan

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