Longevity-Inducing Interventions Change Extracellular Matrix Dynamics in Nematode Worms
How exactly the extracellular matrix is involved in degenerative aging is a topic that remains understudied in comparison to the role of cellular biochemistry in aging. Clearly the matrix changes with age, such as by becoming less elastic, but a deeper understanding of the processes involved is a work in progress. Researchers here report on an investigation of age-related changes in the extracellular matrix, and how those changes are altered by interventions that slow aging. They worked with short-lived nematode worms, the starting point for a great deal of research into the mechanisms of aging, and found some interesting commonalities.
Dysfunctional extracellular matrices (ECM) contribute to aging and disease. Repairing dysfunctional ECM could potentially prevent age-related pathologies. Interventions promoting longevity also impact ECM gene expression. However, the role of ECM composition changes in healthy aging remains unclear. Here we perform proteomics and in-vivo monitoring to systematically investigate ECM composition (matreotype) during aging in C. elegans revealing three distinct collagen dynamics.
Longevity interventions slow age-related collagen stiffening and prolong the expression of collagens that are turned over. These prolonged collagen dynamics are mediated by a mechanical feedback loop of hemidesmosome-containing structures that span from the exoskeletal ECM through the hypodermis, basement membrane ECM, to the muscles, coupling mechanical forces to adjust ECM gene expression and longevity via the transcriptional co-activator YAP-1 across tissues. Our results provide in-vivo evidence that coordinated ECM remodeling through mechanotransduction is required and sufficient to promote longevity, offering potential avenues for interventions targeting ECM dynamics.
How do avoid AGEs in diet: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704564/