ArticleCellular and molecular gastroenterology and hepatology2021
Wnt-induced, TRP53-mediated Cell Cycle Arrest of Precursors Underlies Interstitial Cell of Cajal Depletion During Aging.
Article in Cellular and molecular gastroenterology and hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Impact of acute stress on gastric interstitial cells of Cajal disorder.Frontiers in cell and developmental biology · 2026Article
- Enhanced Spatial Mapping of Mouse Gastric Muscle Layers Using a Modified Swiss Roll Technique.Journal of visualized experiments : JoVE · 2025Article
- The human colon: Evidence for degenerative changes during aging and the physiological consequences.Neurogastroenterology and motility · 2025Review
- Cellular and molecular mechanisms underlying aging-related gastric neuromuscular dysfunction.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2025Review
- Protocol for gene knockdown using siRNA in organotypic cultures of murine gastric muscle.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2024Article
- Improving Gastric Motility in Aging Through EZH2 Inhibition and Preservation of Interstitial Cells of Cajal.Cellular and molecular gastroenterology and hepatology · 2024Article
- CaPhysiological reviews · 2024Review
- Review
- Cellular Senescence, Inflammation, and Cancer in the Gastrointestinal Tract.International journal of molecular sciences · 2023Review
- Wnt Signaling and Aging of the Gastrointestinal Tract.International journal of molecular sciences · 2022Review
- Aging of enteric neuromuscular systems in gastrointestinal tract.Neurogastroenterology and motility · 2022Review
- A narrative review of imatinib-resistant gastrointestinal stromal tumors.Gastrointestinal stromal tumor · 2021Article
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsGastric dysfunction in the elderly may cause reduced food intake, frailty, and increased mortality. The pacemaker and neuromodulator cells interstitial cells of Cajal (ICC) decline with age in humans, and their loss contributes to gastric dysfunction in progeric klotho mice hypomorphic for the anti-aging Klotho protein. The mechanisms of ICC depletion remain unclear. Klotho attenuates Wnt (wingless-type MMTV integration site) signaling. Here, we examined whether unopposed Wnt signaling could underlie aging-associated ICC loss by up-regulating transformation related protein TRP53 in ICC stem cells (ICC-SC).
methodsMice aged 1-107 weeks, klotho mice, APC
resultsThe klotho and aged mice showed similar ICC loss and impaired gastric compliance. ICC-SC decline preceded ICC depletion. Canonical Wnt signaling and TRP53 increased in gastric muscles of klotho and aged mice and middle-aged humans. Overstimulated canonical Wnt signaling increased DNA damage response and TRP53 and reduced ICC-SC self-renewal and gastric ICC. TRP53 induction persistently inhibited G
conclusionsIncreased Wnt signaling causes age-related ICC loss by up-regulating TRP53, which induces persistent ICC-SC cell cycle arrest without up-regulating canonical senescence markers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.