JNK Activity in Somatic Stem Cells Causes Loss of Tissue Homeostasis in the Aging Drosophila Gut
Open accessAbstract
Metazoans employ cytoprotective and regenerative strategies to maintain tissue homeostasis. Understanding the coordination of these strategies is critical to developing accurate models for aging and associated diseases. Here we show that cytoprotective Jun N-terminal kinase (JNK) signaling influences regeneration in the Drosophila gut by directing proliferation of intestinal stem cells (ISCs). Interestingly, this function of JNK contributes to the loss of tissue homeostasis in old and stressed intestines by promoting the accumulation of misdifferentiated ISC daughter cells. Ectopic Delta/Notch signaling in these cells causes their abnormal differentiation but also limits JNK-induced proliferation. Protective JNK signaling and control of cell proliferation and differentiation by Delta/Notch signaling thus have to be carefully balanced to ensure tissue homeostasis. Our findings suggest that this balance is lost in old animals, increasing the potential for neoplastic transformation.
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In Drosophila, dysfunction of the gut and skeletal muscle appear to be primary drivers of aging and mortality.
“In Drosophila, dysfunction of the gut and skeletal muscle appear to be primary drivers of aging and mortality.39,40,41,42”
From Asynchronous, contagious and digital aging (2021) · cites this paper as [39]
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- Authors
- Biteau, B., Hochmuth, C. E., & Jasper, H.
- Affiliations
- University of Rochester (US)
- Corresponding author
- Jasper, Heinrich
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 3
- Issue
- 4
- Pages
- 442-455
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC3225008
- OpenAlex
- W1986932941
- Cited by
- 583
- References
- 47
- Citations by year
- 2026: 27 · 2025: 25 · 2024: 41 · 2023: 40 · 2022: 30 · 2021: 46 · 2020: 45 · 2019: 33 · 2018: 48 · 2017: 36 · 2016: 23 · 2015: 33 · 2014: 34 · 2013: 30 · 2012: 31
- FWCI
- 5.72
- 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, 1786 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 stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Rochester
- Medical Center, University of Rochester
- National Institute on Aging (R01AG028127)
- National Center for Research Resources (S10RR024577)
- 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 › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- JNK signaling, intestinal stem cells, tissue homeostasis, aging, Delta-Notch signaling, stem cell proliferation, stem cell differentiation, cytoprotection, intestinal regeneration, oncogenic transformation
- MeSH terms
- Aging, Animals, Cell Differentiation, Drosophila melanogaster, Homeostasis, Intestinal Mucosa, Intestines, Membrane Proteins, Regeneration, Signal Transduction, Oxidative Stress, Drosophila Proteins, Animals, Genetically Modified, Intracellular Signaling Peptides and Proteins, MAP Kinase Kinase 4, Cell Proliferation, Receptors, Notch, Adult Stem Cells
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