Abstract
Although it is postulated that dysfunctional extracellular matrices (ECM) drive aging and disease, how ECM integrity assures health during aging is unknown. Here, we systematically examined the ECM composition during Caenorhabditis elegans aging revealing three distinct collagen dynamics. We show that age-dependent stiffening of inert collagen was slowed by longevity interventions through replenishing turned-over collagens. In a screen for the regulators that drive this prolonged collagen remodeling, we identify an apparatus that spans from the exoskeletal ECM through the hypodermis, basement membrane ECM, to the muscles, coupling mechanical forces to adjust ECM gene expression across tissues. Heparan sulfate proteoglycan perlecan is the weakest link in this tension-induced communication, uncoupling basement membrane collagen from its integrin receptor during aging. This novel mechanism of mechano-coupling and synchronizing of two functionally distinct and distant ECMs is indispensable for longevity. Thus, besides hormonal or other signaling molecules, mechanotransduction-coordinated ECM remodeling systemically promotes healthy aging.
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