Abstract
Aging induces a series of alterations, specifically a decline in the stature and number of villi and crypts in the small intestine, thus compromising the absorbent capability of the villi. This investigation employed a senolytic combination of dasatinib and quercetin (D+Q) to examine its impact on the intestinal tract of elderly mice. Our findings demonstrate that D+Q treatment leads to a decrease in the expression of p21, p16, and Ki67, while concurrently triggering removal of apoptotic cells within the villi. Additionally, D+Q treatment exhibits the ability to promote growth in both the height and quantity of villi and crypts, along with stimulating nitric oxide (NO) production in aged mice. The study presented a model to assess strategies to alleviate age-related senescence in the intestinal tract of elderly mice. Importantly, D+Q showcases promising potential in enhancing intestinal functionality within the aging.
MeSH terms
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Aging
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Animals
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Antioxidants / therapeutic use
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Cellular Senescence / drug effects
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Dasatinib* / therapeutic use
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Intestinal Mucosa / drug effects
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Intestine, Small* / drug effects
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Intestine, Small* / physiology
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Male
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Mice
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Quercetin* / therapeutic use
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Regeneration* / drug effects
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Tyrosine Kinase Inhibitors / therapeutic use
Substances
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Dasatinib
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Quercetin
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Tyrosine Kinase Inhibitors
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Antioxidants
Grants and funding
Q. L. is supported by the Guangdong Basic and Applied Basic Research Foundation (2021A1515110799 and 2023A1515010144) and Shenzhen Science and Technology Program (JCYJ20220530142000001) and Shenzhen Nanshan District Science and Technology Plan Funding Program (NS2021077). G. F. is supported by the Guangdong Basic and Applied Basic Research Foundation (2020A1515110158), Guangdong Medical Research Foundation (A2021375), Shenzhen Natural Science Foundation (JCYJ20220530141613031), Shenzhen Nanshan District Science and Technology Plan Project (NS2021044) and Huazhong University of Science and Technology Union Shenzhen Hospital Foundation. W. G. is supported by the Shenzhen Nanshan District Science and Technology Plan Project (NS2022042).