PDF(Pubmed)
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.
摘要：
软骨素,一类糖胺聚糖多糖，在细胞外基质中作为蛋白聚糖被发现，在发育过程中的组织形态发生和轴突再生中起着至关重要的作用。摄入软骨素可延长秀丽隐杆线虫的寿命。然而,内源性软骨素在调节寿命和健康方面的作用仍有待研究。这里,我们证明了MIG-22的功能获得突变，软骨素聚合因子（ChPF），结果升高的软骨素水平和显著延长的寿命和健康。重要的是,在mig-22（gf）突变体中观察到的显着寿命取决于SQV-5/软骨素合酶（ChSy），强调软骨素在控制寿命和健康方面的关键作用。此外,mig-22（gf）突变有效抑制了与MIG-17/ADAMTS金属蛋白酶丢失相关的健康跨度降低，基底膜（BM）重塑的关键因素。我们的发现表明，软骨素在MIG-17下游的健康控制中起作用，同时通过独立于MIG-17的途径调节寿命。
