1. Cell Biology
  2. Structural Biology and Molecular Biophysics
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Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in C. elegans

Research Article
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Cite this article as: eLife 2019;8:e43059 doi: 10.7554/eLife.43059

Abstract

Reduced protein homeostasis leading to increased protein instability is a common molecular feature of aging, but it remains unclear whether this is a cause or consequence of the aging process. In neurodegenerative diseases and other amyloidoses, specific proteins self-assemble into amyloid fibrils and accumulate as pathological aggregates in different tissues. More recently, widespread protein aggregation has been described during normal aging. Until now, an extensive characterization of the nature of age-dependent protein aggregation has been lacking. Here, we show that age-dependent aggregates are rapidly formed by newly synthesized proteins and have an amyloid-like structure resembling that of protein aggregates observed in disease. We then demonstrate that age-dependent protein aggregation accelerates the functional decline of different tissues in C. elegans. Together, these findings imply that amyloid-like aggregates contribute to the aging process and therefore could be important targets for strategies designed to maintain physiological functions in the late stages of life.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, 3 and Figure supplements 1, 3, 4, 7, 8 and 9.

Article and author information

Author details

  1. Chaolie Huang

    Protein Aggregation and Aging, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Sara Wagner-Valladolid

    Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Amberley D Stephens

    Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7303-6392
  4. Raimund Jung

    Protein Aggregation and Aging, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Chetan Poudel

    Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Tessa Sinnige

    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9353-126X
  7. Marie C Lechler

    Protein Aggregation and Aging, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Nicole Schlörit

    Protein Aggregation and Aging, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Meng Lu

    Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9311-2666
  10. Romain F Laine

    Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2151-4487
  11. Claire H Michel

    Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Michele Vendruscolo

    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3616-1610
  13. Clemens F Kaminski

    Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5194-0962
  14. Gabriele S Kaminski Schierle

    Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    gsk20@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  15. Della C David

    Protein Aggregation and Aging, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
    For correspondence
    della.david@dzne.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8597-9470

Funding

Deutsches Zentrum für Neurodegenerative Erkrankungen

  • Della C David

Biotechnology and Biological Sciences Research Council (BB/R021805/1)

  • Romain F Laine

European Commission (Marie Curie International Reintegration grant 322120)

  • Della C David

Engineering and Physical Sciences Research Council

  • Clemens F Kaminski

Wellcome (203249/Z/16/Z)

  • Gabriele S Kaminski Schierle

Medical Research Council (MR/N012453/1)

  • Gabriele S Kaminski Schierle

Alzheimer's Research UK (ARUK-PG2013-14)

  • Gabriele S Kaminski Schierle

Infinitus China Ltd

  • Clemens F Kaminski
  • Gabriele S Kaminski Schierle

Alzheimer's Research UK (Travel grant)

  • Amberley D Stephens

Biotechnology and Biological Sciences Research Council (BB/P027431/1)

  • Romain F Laine

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. John Kuriyan, University of California, Berkeley, United States

Publication history

  1. Received: October 22, 2018
  2. Accepted: May 2, 2019
  3. Accepted Manuscript published: May 3, 2019 (version 1)
  4. Version of Record published: May 17, 2019 (version 2)

Copyright

© 2019, Huang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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