Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in C. elegans
- German Center for Neurodegenerative Diseases (DZNE), Germany
- University of Cambridge, United Kingdom
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
Amberley D Stephens
Michele Vendruscolo
Clemens F Kaminski
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.
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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Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in C. elegans
eLife 8:e43059.
https://doi.org/10.7554/eLife.43059
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