Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in Caenorhabditis elegans
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 a...
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doaj-d304ea99735c4d8ea67842213713ac7f2021-05-05T17:35:10ZengeLife Sciences Publications LtdeLife2050-084X2019-05-01810.7554/eLife.43059Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in Caenorhabditis elegansChaolie Huang0Sara Wagner-Valladolid1Amberley D Stephens2https://orcid.org/0000-0002-7303-6392Raimund Jung3Chetan Poudel4Tessa Sinnige5https://orcid.org/0000-0002-9353-126XMarie C Lechler6Nicole Schlörit7Meng Lu8https://orcid.org/0000-0001-9311-2666Romain F Laine9https://orcid.org/0000-0002-2151-4487Claire H Michel10Michele Vendruscolo11https://orcid.org/0000-0002-3616-1610Clemens F Kaminski12https://orcid.org/0000-0002-5194-0962Gabriele S Kaminski Schierle13https://orcid.org/0000-0002-1843-2202Della C David14https://orcid.org/0000-0001-8597-9470German Center for Neurodegenerative Diseases (DZNE), Tübingen, GermanyDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United KingdomDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United KingdomGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, GermanyDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United KingdomDepartment of Chemistry, University of Cambridge, Cambridge, United KingdomGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Graduate Training Centre of Neuroscience, University of Tübingen, Tübingen, GermanyGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Graduate Training Centre of Neuroscience, University of Tübingen, Tübingen, GermanyDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United KingdomDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United KingdomDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United KingdomDepartment of Chemistry, University of Cambridge, Cambridge, United KingdomDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United KingdomDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United KingdomGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, GermanyReduced 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.https://elifesciences.org/articles/43059protein aggregationagingamyloid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chaolie Huang Sara Wagner-Valladolid Amberley D Stephens Raimund Jung Chetan Poudel Tessa Sinnige Marie C Lechler Nicole Schlörit Meng Lu Romain F Laine Claire H Michel Michele Vendruscolo Clemens F Kaminski Gabriele S Kaminski Schierle Della C David |
spellingShingle |
Chaolie Huang Sara Wagner-Valladolid Amberley D Stephens Raimund Jung Chetan Poudel Tessa Sinnige Marie C Lechler Nicole Schlörit Meng Lu Romain F Laine Claire H Michel Michele Vendruscolo Clemens F Kaminski Gabriele S Kaminski Schierle Della C David Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in Caenorhabditis elegans eLife protein aggregation aging amyloid |
author_facet |
Chaolie Huang Sara Wagner-Valladolid Amberley D Stephens Raimund Jung Chetan Poudel Tessa Sinnige Marie C Lechler Nicole Schlörit Meng Lu Romain F Laine Claire H Michel Michele Vendruscolo Clemens F Kaminski Gabriele S Kaminski Schierle Della C David |
author_sort |
Chaolie Huang |
title |
Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in Caenorhabditis elegans |
title_short |
Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in Caenorhabditis elegans |
title_full |
Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in Caenorhabditis elegans |
title_fullStr |
Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in Caenorhabditis elegans |
title_full_unstemmed |
Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in Caenorhabditis elegans |
title_sort |
intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in caenorhabditis elegans |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2019-05-01 |
description |
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. |
topic |
protein aggregation aging amyloid |
url |
https://elifesciences.org/articles/43059 |
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