학술논문
Tissue-specific landscape of protein aggregation and quality control in an aging vertebrate.
Document Type
Academic Journal
Author
Chen YR; Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.; Harel I; The Silberman Institute, the Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel; Department of Genetics, Stanford University, Stanford, CA 94305, USA.; Singh PP; Department of Genetics, Stanford University, Stanford, CA 94305, USA.; Ziv I; Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.; Moses E; The Silberman Institute, the Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel.; Goshtchevsky U; The Silberman Institute, the Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel.; Machado BE; Department of Genetics, Stanford University, Stanford, CA 94305, USA.; Brunet A; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Glenn Center for the Biology of Aging, Stanford University, Stanford, CA 94305, USA. Electronic address: anne.brunet@stanford.edu.; Jarosz DF; Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: jarosz@stanford.edu.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 101120028 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1551 (Electronic) Linking ISSN: 15345807 NLM ISO Abbreviation: Dev Cell Subsets: MEDLINE
Subject
Language
English
Abstract
Protein aggregation is a hallmark of age-related neurodegeneration. Yet, aggregation during normal aging and in tissues other than the brain is poorly understood. Here, we leverage the African turquoise killifish to systematically profile protein aggregates in seven tissues of an aging vertebrate. Age-dependent aggregation is strikingly tissue specific and not simply driven by protein expression differences. Experimental interrogation in killifish and yeast, combined with machine learning, indicates that this specificity is linked to protein-autonomous biophysical features and tissue-selective alterations in protein quality control. Co-aggregation of protein quality control machinery during aging may further reduce proteostasis capacity, exacerbating aggregate burden. A segmental progeria model with accelerated aging in specific tissues exhibits selectively increased aggregation in these same tissues. Intriguingly, many age-related protein aggregates arise in wild-type proteins that, when mutated, drive human diseases. Our data chart a comprehensive landscape of protein aggregation during vertebrate aging and identify strong, tissue-specific associations with dysfunction and disease.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 Elsevier Inc. All rights reserved.)