Endogenous chondroitin extends lifespan by inhibiting VHA-7-mediated tubular lysosome formation.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Lysosomes*/metabolism ; Lysosomes*/drug effects ; Caenorhabditis elegans*/metabolism ; Caenorhabditis elegans*/drug effects ; Chondroitin*/metabolism ; Caenorhabditis elegans Proteins*/metabolism ; Caenorhabditis elegans Proteins*/genetics ; Longevity*/drug effects; Animals ; Mutation ; Basement Membrane/metabolism ; Basement Membrane/drug effects
    • 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.
      Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
      (© 2024. The Author(s).)
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    • Grant Information:
      22K20658 Ministry of Education, Culture, Sports, Science and Technology; 24H01981 Ministry of Education, Culture, Sports, Science and Technology; Individual Special Research Subsidy Kwansei Gakuin University; advancement of natural science Naito Grant
    • Contributed Indexing:
      Keywords: Aging; Basement membrane; Chondroitin; Hemidesmosomes; Tubular lysosomes
    • Accession Number:
      9007-27-6 (Chondroitin)
      0 (Caenorhabditis elegans Proteins)
    • Publication Date:
      Date Created: 20241128 Date Completed: 20241128 Latest Revision: 20241202
    • Publication Date:
      20241204
    • Accession Number:
      PMC11605119
    • Accession Number:
      10.1038/s41598-024-80242-3
    • Accession Number:
      39609482