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Updated: Dec 31, 2025
10:57
Isolating Intestinal Stem Cells from Adult Drosophila Midguts by FACS to Study Stem Cell Behavior During Aging
Published on: December 16, 2014
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Gut stem cell aging is driven by mTORC1 via a p38 MAPK-p53 pathway
Dan He1, Hongguang Wu1, Jinnan Xiang1
1Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200240, China.
Nature Communications
|January 4, 2020
Summary
Aging intestinal villi, crucial for nutrient absorption, decline due to mTORC1 activation in gut stem cells. Targeting the p38 MAPK pathway may reverse this aging process and improve absorption.
Area of Science:
- Gastroenterology
- Cellular Biology
- Aging Research
Background:
- Intestinal villi are vital for nutrient absorption, but aging leads to malabsorption and illness.
- The precise mechanisms driving intestinal aging remain largely unknown.
- Understanding gut aging is crucial for addressing age-related digestive disorders.
Purpose of the Study:
- To elucidate the molecular mechanisms regulating intestinal villus aging.
- To investigate the role of mTORC1 in the aging of intestinal stem cells.
- To identify potential therapeutic targets for reversing gut aging.
Main Methods:
- Analysis of intestinal stem and progenitor cells in geriatric mice.
- Utilizing intestinal stem cell-specific Tsc1 knockout mouse models.
- Investigating the mTORC1-MKK6-p38 MAPK-p53 signaling pathway.
- Assessing the impact of targeting p38 MAPK and p53 on gut aging phenotypes.
Main Results:
- mTORC1 is highly activated in geriatric mouse intestinal stem and progenitor cells.
- mTORC1 activation drives villus structural and functional decline via MKK6 and p38 MAPK-p53.
- Targeting p38 MAPK or p53 ameliorates aging phenotypes in intestinal stem cells and villi.
- Nutrient absorption defects associated with aging are reversed by targeting these pathways.
Conclusions:
- mTORC1 signaling in gut stem cells is a key driver of intestinal aging.
- The p38 MAPK-p53 pathway is a critical downstream mediator of mTORC1-induced gut aging.
- p38 MAPK represents a promising therapeutic target for combating intestinal aging and malabsorption.
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