Endogenous chondroitin extends the lifespan and healthspan in C. elegans
Abstract Chondroitin, a class of glycosaminoglycan polysaccharides, is found as proteoglycans in the extracellular matrix, plays a crucial role in tissue morphogenesis during development and axonal regeneration. Ingestion of chondroitin prolongs the lifespan of C. elegans. However, the roles of endo...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-55417-7 |
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| author | Yukimasa Shibata Yuri Tanaka Hiroyuki Sasakura Yuki Morioka Toshihiro Sassa Shion Fujii Kaito Mitsuzumi Masashi Ikeno Yukihiko Kubota Kenji Kimura Hidenao Toyoda Kosei Takeuchi Kiyoji Nishiwaki |
| author_facet | Yukimasa Shibata Yuri Tanaka Hiroyuki Sasakura Yuki Morioka Toshihiro Sassa Shion Fujii Kaito Mitsuzumi Masashi Ikeno Yukihiko Kubota Kenji Kimura Hidenao Toyoda Kosei Takeuchi Kiyoji Nishiwaki |
| author_sort | Yukimasa Shibata |
| collection | DOAJ |
| description | Abstract Chondroitin, a class of glycosaminoglycan polysaccharides, is found as proteoglycans in the extracellular matrix, plays a crucial role in tissue morphogenesis during development and axonal regeneration. Ingestion of chondroitin prolongs the lifespan of C. elegans. However, the roles of endogenous chondroitin in regulating lifespan and healthspan mostly remain to be investigated. Here, we demonstrate that a gain-of-function mutation in MIG-22, the chondroitin polymerizing factor (ChPF), results in elevated chondroitin levels and a significant extension of both the lifespan and healthspan in C. elegans. Importantly, the remarkable longevity observed in mig-22(gf) mutants is dependent on SQV-5/chondroitin synthase (ChSy), highlighting the pivotal role of chondroitin in controlling both lifespan and healthspan. Additionally, the mig-22(gf) mutation effectively suppresses the reduced healthspan associated with the loss of MIG-17/ADAMTS metalloprotease, a crucial for factor in basement membrane (BM) remodeling. Our findings suggest that chondroitin functions in the control of healthspan downstream of MIG-17, while regulating lifespan through a pathway independent of MIG-17. |
| first_indexed | 2024-03-07T15:09:13Z |
| format | Article |
| id | doaj.art-8308e5ea29854c29ade144db31b71445 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:09:13Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-8308e5ea29854c29ade144db31b714452024-03-05T18:46:20ZengNature PortfolioScientific Reports2045-23222024-02-0114111110.1038/s41598-024-55417-7Endogenous chondroitin extends the lifespan and healthspan in C. elegansYukimasa Shibata0Yuri Tanaka1Hiroyuki Sasakura2Yuki Morioka3Toshihiro Sassa4Shion Fujii5Kaito Mitsuzumi6Masashi Ikeno7Yukihiko Kubota8Kenji Kimura9Hidenao Toyoda10Kosei Takeuchi11Kiyoji Nishiwaki12Department of Biomedical Sciences, Kwansei Gakuin UniversityDepartment of Biomedical Sciences, Kwansei Gakuin UniversityDepartment of Medical Cell Biology, School of Medicine, Aichi Medical UniversityDepartment of Medical Cell Biology, School of Medicine, Aichi Medical UniversityRIKEN Center for Developmental BiologyDepartment of Biomedical Sciences, Kwansei Gakuin UniversityDepartment of Biomedical Sciences, Kwansei Gakuin UniversityDepartment of Medical Cell Biology, School of Medicine, Aichi Medical UniversityDepartment of Biomedical Sciences, Kwansei Gakuin UniversityDepartment of Biomedical Sciences, Kwansei Gakuin UniversityLaboratory of Bio-Analytical Chemistry, College of Pharmaceutical Sciences, Ritsumeikan UniversityDepartment of Medical Cell Biology, School of Medicine, Aichi Medical UniversityDepartment of Biomedical Sciences, Kwansei Gakuin UniversityAbstract Chondroitin, a class of glycosaminoglycan polysaccharides, is found as proteoglycans in the extracellular matrix, plays a crucial role in tissue morphogenesis during development and axonal regeneration. Ingestion of chondroitin prolongs the lifespan of C. elegans. However, the roles of endogenous chondroitin in regulating lifespan and healthspan mostly remain to be investigated. Here, we demonstrate that a gain-of-function mutation in MIG-22, the chondroitin polymerizing factor (ChPF), results in elevated chondroitin levels and a significant extension of both the lifespan and healthspan in C. elegans. Importantly, the remarkable longevity observed in mig-22(gf) mutants is dependent on SQV-5/chondroitin synthase (ChSy), highlighting the pivotal role of chondroitin in controlling both lifespan and healthspan. Additionally, the mig-22(gf) mutation effectively suppresses the reduced healthspan associated with the loss of MIG-17/ADAMTS metalloprotease, a crucial for factor in basement membrane (BM) remodeling. Our findings suggest that chondroitin functions in the control of healthspan downstream of MIG-17, while regulating lifespan through a pathway independent of MIG-17.https://doi.org/10.1038/s41598-024-55417-7AgingChondroitinADAMTS proteaseBasement membrane |
| spellingShingle | Yukimasa Shibata Yuri Tanaka Hiroyuki Sasakura Yuki Morioka Toshihiro Sassa Shion Fujii Kaito Mitsuzumi Masashi Ikeno Yukihiko Kubota Kenji Kimura Hidenao Toyoda Kosei Takeuchi Kiyoji Nishiwaki Endogenous chondroitin extends the lifespan and healthspan in C. elegans Scientific Reports Aging Chondroitin ADAMTS protease Basement membrane |
| title | Endogenous chondroitin extends the lifespan and healthspan in C. elegans |
| title_full | Endogenous chondroitin extends the lifespan and healthspan in C. elegans |
| title_fullStr | Endogenous chondroitin extends the lifespan and healthspan in C. elegans |
| title_full_unstemmed | Endogenous chondroitin extends the lifespan and healthspan in C. elegans |
| title_short | Endogenous chondroitin extends the lifespan and healthspan in C. elegans |
| title_sort | endogenous chondroitin extends the lifespan and healthspan in c elegans |
| topic | Aging Chondroitin ADAMTS protease Basement membrane |
| url | https://doi.org/10.1038/s41598-024-55417-7 |
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