Tissue-Specific Activities of C. elegans DAF-16 in the Regulation of Lifespan
Open accessAbstract
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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Reduced IIS specifically in the nervous system is sufficient to extend lifespan in several model systems.
“Importantly, reduced IIS specifically in the nervous system is sufficient to extend lifespan in several model systems.”
From Neural mechanisms of ageing and cognitive decline (2010) · cites this paper as [65]
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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)
- 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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