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.
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http://dx.doi.org/10.1038/s41598-024-80242-3 | DOI Listing |
Langmuir
December 2024
Division of Craniofacial Function Engineering (Division of Biomaterials Science and Engineering), Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
This study was designed to investigate how the strength of the interaction between octacalcium phosphate (OCP) and modified chondroitin-A sulfate (CS-A), a glycosaminoglycan, regulates the adsorption-desorption of cytokines and subsequently affects the osteoblastic differentiation of mesenchymal stem cells (MSCs) in vitro. The utilization of cytokines produced by cells, such as macrophages, stimulated by the hydrolysis of OCP, is expected to enhance the bone regeneration capacity of the OCP. CS-Na was used to modify CS-A on the OCP immobilized with the amino group through electrostatic interactions.
View Article and Find Full Text PDFPLoS One
December 2024
Unconventional Computing Lab, University of the West of England, Bristol, United Kingdom.
Proteinoids-thermal proteins-are produced by heating amino acids to their melting point and initiation of polymerisation to produce polymeric chains. Proteinoids swell in aqueous solution into hollow microspheres. The proteinoid microspheres produce endogenous burst of electrical potential spikes and change patterns of their electrical activity in response to illumination.
View Article and Find Full Text PDFSci Rep
November 2024
Department of Biomedical Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda, Hyogo, Japan.
ACS Appl Mater Interfaces
November 2024
School of Pharmacy, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui 230031, China.
Acute kidney injury (AKI) is a dynamic process associated with inflammation, oxidative stress, and lipid peroxidation, in which mitochondrial mitophagy and macrophage polarization play a critical role in the pathophysiology. Based on the expression of the CD44 receptor on renal tubular epithelial cells (RTECs) and activated M1 macrophages being abnormally increased, accompanied by up-regulation of reactive oxygen species (ROS) during AKI, the conjugates of bilirubin (BR), an endogenous antioxidant which has the property of anti-inflammation, and chondroitin sulfate (CS) with CD44-targeting property could be a promising therapeutic carrier. In this study, we develop a CD44-targeted/ROS-responsive CS-BR-mediated multifunctional liposome loading celastrol (CS-BR@CLT) for the targeted therapy of AKI.
View Article and Find Full Text PDFSmall
December 2024
Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
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