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

Alina C Teuscher | Cyril Statzer | Anita Goyala | Seraina A Domenig | Ingmar Schoen | Max Hess | Alexander M Hofer | Andrea Fossati | Viola Vogel | Orcun Goksel | Ruedi Aebersold | Collin Y Ewald
Nature communications | 2024

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.

Pubmed ID: 38177158

Research resources used in this publication

Antibodies used in this publication

None found

Associated grants

  • Agency: NIH HHS, United States
    Id: P40 OD010440

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Promega (tool)

RRID:SCR_006724

An Antibody supplier

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Sigma-Aldrich (tool)

RRID:SCR_008988

American chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.

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Program to Reduce Incontinence by Diet and Exercise (tool)

RRID:SCR_009018

Randomized controlled trial being conducted at two clinical centers in the United States to learn more about the effects of weight loss on urinary incontinence. About 330 overweight women aged 30 or older will participate and will be followed for 18 months. Efficacy of weight reduction as a treatment for urinary incontinence will be examined at 6 months following the intensive weight control program, and the sustained impact of the intervention will be examined at 18 months. To increase the maintenance of weight reduction and facilitate evaluation of the enduring impact of weight loss on urinary incontinence, they propose to study a motivation-based weight maintenance program. At the end of the intensive weight control program, women randomized to the weight loss program will be randomized to either a 12-month skill-based maintenance intervention or to a motivation-based maintenance intervention. The maintenance interventions maximize the potential for sustained weight loss and will allow them to determine if long-term weight reduction will produce continued improvement in urinary incontinence.

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Inkscape (tool)

RRID:SCR_014479

A vector graphics software which runs on Windows, Mac OS X and GNU/Linux. It can import and export various file formats, including SVG, AI, EPS, PDF, PS and PNG. Features include object creation, object manipulation, color editing, and text editing.

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ggplot2 (tool)

RRID:SCR_014601

Open source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.

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BC13623 (organism)

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Caenorhabditis elegans with name dpy-5(e907) I; sEx13623. from WB.

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Caenorhabditis elegans with name Whole-genome sequenced strain. from WB.

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Caenorhabditis elegans with name unc-119(ed4) III; qyIs10 IV. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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BC13560 (organism)

RRID:WB-STRAIN:WBStrain00002642

Caenorhabditis elegans with name dpy-5(e907) I; sIs13559. from WB.

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Caenorhabditis elegans with name Whole-genome sequenced strain. from WB.

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Caenorhabditis elegans with name mltn-13(gk766) X. from WB.

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Caenorhabditis elegans with name tln-1(n1338) I. from WB.

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Caenorhabditis elegans with name cle-1(gk364) I. from WB.

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Caenorhabditis elegans with name dgn-2(ok209) dgn-3(tm1092) dgn-1(cg121) X; cgEx308. from WB.

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NK860 (organism)

RRID:WB-STRAIN:WBStrain00028884

Caenorhabditis elegans with name unc-119(ed4) III; qyIs161. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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RP247 (organism)

RRID:WB-STRAIN:WBStrain00033419

Caenorhabditis elegans with name trIs30. from WB.

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MH2051 (organism)

RRID:WB-STRAIN:WBStrain00026524

Caenorhabditis elegans with name kuIs55. from WB.

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BT24 (organism)

RRID:WB-STRAIN:WBStrain00003954

Caenorhabditis elegans with name rhIs23 III. from WB.

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RRID:WB-STRAIN:WBStrain00002390

Caenorhabditis elegans with name dpy-5(e907) I; sIs11600. from WB.

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RRID:WB-STRAIN:WBStrain00033503

Caenorhabditis elegans with name pat-2(st538) unc-32(e189) III; stEx10. from WB.

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RRID:WB-STRAIN:WBStrain00035602

Caenorhabditis elegans with name gpn-1(ok377) X. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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RRID:WB-STRAIN:WBStrain00004465

Caenorhabditis elegans with name lon-2(e678) mec-5(e1504) X. from WB.

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RRID:WB-STRAIN:WBStrain00004667

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RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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RRID:WB-STRAIN:WBStrain00005037

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RRID:WB-STRAIN:WBStrain00028866

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RRID:WB-STRAIN:WBStrain00004531

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