Longevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans


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Date

2024-01-04

Publication Type

Journal Article

ETH Bibliography

yes

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Abstract

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.

Publication status

published

Editor

Book title

Volume

15 (1)

Pages / Article No.

276

Publisher

Nature

Event

Edition / version

Methods

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Geographic location

Date collected

Date created

Subject

Organisational unit

03640 - Vogel, Viola / Vogel, Viola check_circle
09598 - Ewald, Collin Y. (ehemalig) / Ewald, Collin Y. (former)

Notes

Funding

163898 - The role of extracellular matrix enhancement in promoting healthy aging (SNF)
190072 - Protein homeostasis of extracellular proteins during aging (SNF)
670821 - Proteomics 4D: The proteome in context (EC)

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