| RRC ID |
80846
|
| Author |
Teuscher AC, Statzer C, Goyala A, Domenig SA, Schoen I, Hess M, Hofer AM, Fossati A, Vogel V, Goksel O, Aebersold R, Ewald CY.
|
| Title |
Longevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans.
|
| Journal |
Nat Commun
|
| 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.
|
| Volume |
15(1)
|
| Pages |
276
|
| Published |
2024-1-4
|
| DOI |
10.1038/s41467-023-44409-2
|
| PII |
10.1038/s41467-023-44409-2
|
| PMID |
38177158
|
| PMC |
PMC10766642
|
| MeSH |
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
Collagen / metabolism
Extracellular Matrix / metabolism
Homeostasis
Longevity* / physiology
Mechanotransduction, Cellular
Transcription Factors / genetics
Transcription Factors / metabolism
YAP-Signaling Proteins
|
| Resource |
| C.elegans |
tm8818
tm1416
tm6673
tm548
tm385
tm1092 |
