Royal College of Surgeons in Ireland
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Longevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans.pdf (11.2 MB)

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

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posted on 2024-02-01, 12:05 authored by Alina C Teuscher, Cyril Statzer, Anita Goyala, Seraina A Domenig, Ingmar SchoenIngmar Schoen, Max Hess, Alexander M Hofer, Andrea Fossati, Viola Vogel, Orcun Goksel, Ruedi Aebersold, Collin Y Ewald

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. 

Funding

Open access funding provided by Swiss Federal Institute of Technology Zurich

History

Data Availability Statement

The data generated in this study are provided in the article and its Supplementary Data 1-14. Data are available via ProteomeXchange with the identifier PXD046470

Comments

The original article is available at https://www.nature.com/

Published Citation

Teuscher AC, et al. Longevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans. Nat Commun. 2024;15(1):276.

Publication Date

4 January 2024

PubMed ID

38177158

Department/Unit

  • School of Pharmacy and Biomolecular Sciences
  • Irish Centre for Vascular Biology

Publisher

Springer Nature Limited

Version

  • Published Version (Version of Record)