Autophagy inhibitor 3-methyladenine mitigates the severity of colitis in aged mice by inhibiting autophagy
Background: The elderly ulcerative colitis (UC) patients pose unique challenges due to their comorbidities, diminished functional capacity, and heightened risk of treatment-related complications. Thus, finding a safe and effective treatment for this age group is crucial. Aim: This study investigates...
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Elsevier
2025-03-01
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| Series: | Experimental Gerontology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0531556525000257 |
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| author | Ailing Liu Hongying Wang Hong Lv Hong Yang Yue Li Jiaming Qian |
| author_facet | Ailing Liu Hongying Wang Hong Lv Hong Yang Yue Li Jiaming Qian |
| author_sort | Ailing Liu |
| collection | DOAJ |
| description | Background: The elderly ulcerative colitis (UC) patients pose unique challenges due to their comorbidities, diminished functional capacity, and heightened risk of treatment-related complications. Thus, finding a safe and effective treatment for this age group is crucial. Aim: This study investigates the role of autophagy in the pathogenesis of UC in young and elderly patients, and explores the therapeutic potential and mechanisms of autophagy modulators in aged mice with dextran sulfate sodium (DSS)-induced colitis. Methods: Colonic biopsies were collected from young and old UC patients as well as comparable healthy subjects. Young (6–8 weeks) and aged (56 weeks) C57BL/6 mice were treated with DSS to induce acute colitis model. The autophagy inhibitor 3-methyladenine was administered intraperitoneally to aged DSS-induced mice. The autophagy activity was detected by the protein expressions of LC3B-II, p62 and ATG5 by western blot and immunohistochemistry. The levels of TNF -α, IL-6, CCL4, CXCL12 and CD86 were measured by qRT-PCR. The transcriptional activity of NF-κB was measured by electrophoretic mobility shift assay (EMSA). Results: Increased autophagy activity was observed in aged DSS-induced mice. Treatment with 3-methyladenine suppressed autophagy in intestinal epithelial cells (IECs) and alleviated colitis severity. Additionally, 3-methyladenine reduced macrophage recruitment, decreased IL-6 levels, and inhibited NF-κB signaling, thereby mitigating inflammation. Conclusion: Significant differences in autophagy activity were identified between young and aged DSS-induced mice. These findings underscore the potential therapeutic benefits of autophagy inhibition in elderly UC patients. |
| format | Article |
| id | doaj-art-3f88727446e540c2a6a9474df3a79f90 |
| institution | Kabale University |
| issn | 1873-6815 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Experimental Gerontology |
| spelling | doaj-art-3f88727446e540c2a6a9474df3a79f902025-02-04T04:10:18ZengElsevierExperimental Gerontology1873-68152025-03-01201112697Autophagy inhibitor 3-methyladenine mitigates the severity of colitis in aged mice by inhibiting autophagyAiling Liu0Hongying Wang1Hong Lv2Hong Yang3Yue Li4Jiaming Qian5Department of Gastroenterology, the Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong Province, China; Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Molecular Oncology, Peking Union Medical College, Beijing, ChinaDepartment of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Corresponding author at: Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan Road, Dongcheng District, Beijing 100730, China.Background: The elderly ulcerative colitis (UC) patients pose unique challenges due to their comorbidities, diminished functional capacity, and heightened risk of treatment-related complications. Thus, finding a safe and effective treatment for this age group is crucial. Aim: This study investigates the role of autophagy in the pathogenesis of UC in young and elderly patients, and explores the therapeutic potential and mechanisms of autophagy modulators in aged mice with dextran sulfate sodium (DSS)-induced colitis. Methods: Colonic biopsies were collected from young and old UC patients as well as comparable healthy subjects. Young (6–8 weeks) and aged (56 weeks) C57BL/6 mice were treated with DSS to induce acute colitis model. The autophagy inhibitor 3-methyladenine was administered intraperitoneally to aged DSS-induced mice. The autophagy activity was detected by the protein expressions of LC3B-II, p62 and ATG5 by western blot and immunohistochemistry. The levels of TNF -α, IL-6, CCL4, CXCL12 and CD86 were measured by qRT-PCR. The transcriptional activity of NF-κB was measured by electrophoretic mobility shift assay (EMSA). Results: Increased autophagy activity was observed in aged DSS-induced mice. Treatment with 3-methyladenine suppressed autophagy in intestinal epithelial cells (IECs) and alleviated colitis severity. Additionally, 3-methyladenine reduced macrophage recruitment, decreased IL-6 levels, and inhibited NF-κB signaling, thereby mitigating inflammation. Conclusion: Significant differences in autophagy activity were identified between young and aged DSS-induced mice. These findings underscore the potential therapeutic benefits of autophagy inhibition in elderly UC patients.http://www.sciencedirect.com/science/article/pii/S0531556525000257Cell autophagySenescenceInflammatory bowel diseaseMacrophagyInflammation |
| spellingShingle | Ailing Liu Hongying Wang Hong Lv Hong Yang Yue Li Jiaming Qian Autophagy inhibitor 3-methyladenine mitigates the severity of colitis in aged mice by inhibiting autophagy Experimental Gerontology Cell autophagy Senescence Inflammatory bowel disease Macrophagy Inflammation |
| title | Autophagy inhibitor 3-methyladenine mitigates the severity of colitis in aged mice by inhibiting autophagy |
| title_full | Autophagy inhibitor 3-methyladenine mitigates the severity of colitis in aged mice by inhibiting autophagy |
| title_fullStr | Autophagy inhibitor 3-methyladenine mitigates the severity of colitis in aged mice by inhibiting autophagy |
| title_full_unstemmed | Autophagy inhibitor 3-methyladenine mitigates the severity of colitis in aged mice by inhibiting autophagy |
| title_short | Autophagy inhibitor 3-methyladenine mitigates the severity of colitis in aged mice by inhibiting autophagy |
| title_sort | autophagy inhibitor 3 methyladenine mitigates the severity of colitis in aged mice by inhibiting autophagy |
| topic | Cell autophagy Senescence Inflammatory bowel disease Macrophagy Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0531556525000257 |
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