Abstract

Chondroitin extends lifespan and healthspan in C. elegans, but the relationship between extracellular chondroitin and intracellular anti-aging mechanisms is unknown. The basement membrane (BM) that contains chondroitin proteoglycans is anchored to cells via hemidesmosomes (HDs), and it accumulates damage with aging. In this study, we found that chondroitin regulates aging through the formation of HDs and inhibition of tubular lysosomes (TLs). Reduction of chondroitin due to a mutation in sqv-5/Chondroitin synthase (ChSy) causes the earlier and excessive formation of TLs and leakage of the lysosomal nuclease in a manner dependent on VHA-7, the a-subunit of V-type ATPase. VHA-7, whose mutation suppresses the short lifespan of the sqv-5 mutant, is initially localized to the basal side of the hypodermal cells and transported to lysosomes with aging. These results demonstrate that endogenous chondroitin suppresses aging by inhibiting the earlier excessive formation of TLs. This is a novel anti-aging mechanism that is controlled by the BM.

Details

Title
Endogenous chondroitin extends lifespan by inhibiting VHA-7-mediated tubular lysosome formation
Author
Shibata, Yukimasa 1 ; Tanaka, Yuri 2 ; Mori, Shunsuke 2 ; Mitsuzumi, Kaito 2 ; Fujii, Shion 2 ; Sasakura, Hiroyuki 3 ; Morioka, Yuki 3 ; Sugioka, Kenji 4 ; Takeuchi, Kosei 3 ; Nishiwaki, Kiyoji 2 

 Kwansei Gakuin University, Department of Biomedical Sciences, Sanda, Japan (GRID:grid.258777.8) (ISNI:0000 0001 2295 9421); Gakuen Uegahara, Sanda, Japan (GRID:grid.258777.8) 
 Kwansei Gakuin University, Department of Biomedical Sciences, Sanda, Japan (GRID:grid.258777.8) (ISNI:0000 0001 2295 9421) 
 Aichi Medical University, Department of Medical Cell Biology, School of Medicine, Nagakute, Japan (GRID:grid.411234.1) (ISNI:0000 0001 0727 1557) 
 The University of British Columbia, Life Sciences Institute, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
Pages
29651
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3133926135
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.