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Cited by 649Genetics, Aging, and Longevity in Model OrganismsHeat shock proteins researchAutophagy in Disease and Therapy

Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging

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Ben-Zvi, Anat, Miller, Elizabeth A., Morimoto, Richard I.·2009·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0902882106PMC PMC2736453
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Abstract

Protein damage contributes prominently to cellular aging. To address whether this occurs at a specific period during aging or accumulates gradually, we monitored the biochemical, cellular, and physiological properties of folding sensors expressed in different tissues of C. elegans . We observed the age-dependent misfolding and loss of function of diverse proteins harboring temperature-sensitive missense mutations in all somatic tissues at the permissive condition. This widespread failure in proteostasis occurs rapidly at an early stage of adulthood, and coincides with a severely reduced activation of the cytoprotective heat shock response and the unfolded protein response. Enhancing stress responsive factors HSF-1 or DAF-16 suppresses misfolding of these metastable folding sensors and restores the ability of the cell to maintain a functional proteome. This suggests that a compromise in the regulation of proteostatic stress responses occurs early in adulthood and tips the balance between the load of damaged proteins and the proteostasis machinery. We propose that the collapse of proteostasis represents an early molecular event of aging that amplifies protein damage in age-associated diseases of protein conformation.

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  • During division of NSCs, lysosomes are asymmetrically distributed between daughter cells.

    “During division of NSCs, lysosomes are asymmetrically distributed between daughter cells.”

    From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [18]

    The Results discuss dynamin function in C. elegans neurons and coelomocytes during aging, not neural stem-cell division. Searches for lysosomes, asymmetric segregation, and daughter cells found no passage addressing the claim; page numbers are unavailable in our copy. (LLM, conf=0.78)

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  • The daughter cell that receives more lysosomes cleaves and activates more Notch signaling in the lysosome, which contributes to maintaining stemness.

    “The daughter cell that receives more lysosomes cleaves and activates more Notch signaling in the lysosome, which contributes to maintaining “stemness.””

    From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [18]

    The Results and Discussion passages address age-related proteostasis in C. elegans, not unequal lysosome inheritance by daughter cells. Searches for lysosomes, Notch cleavage, and stemness found no passage in our copy addressing the claim. Page numbers were unavailable. (LLM, conf=0.78)

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  • The other daughter cell with fewer lysosomes and less Notch signaling migrates and differentiates.

    “The other daughter cell with fewer lysosomes and less Notch signaling migrates and differentiates.18”

    From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [18]

    The Results discuss age-related loss of protein function in C. elegans neurons and coelomocytes, not daughter-cell fate. Searches for lysosomes, Notch signaling, and daughter-cell migration or differentiation found no passage addressing the claim. (LLM, conf=0.76)

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Authors
Ben-Zvi, A., Miller, E. A., & Morimoto, R. I.
Affiliations
  • Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208
  • Northwestern University (US)
Corresponding author
Morimoto, Richard I.
ORCID
Morimoto, Richard I.
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2009-09
Volume
106
Issue
35
Pages
14914-14919
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0902882106
PMC
PMC2736453
OpenAlex
W2152217159
Cited by
649
References
2
Citations by year
2026: 29 · 2025: 32 · 2024: 31 · 2023: 31 · 2022: 50 · 2021: 41 · 2020: 39 · 2019: 41 · 2018: 27 · 2017: 50 · 2016: 45 · 2015: 46 · 2014: 54 · 2013: 31 · 2012: 34
FWCI
10.33
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • Directorate for Biological Sciences
  • National Institute on Aging (R01AG026647)
  • National Institute of General Medical Sciences (R37GM038109)
  • National Institute of Child Health and Human Development
  • National Center for Research Resources
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
proteostasis, aging, protein misfolding, heat shock response, unfolded protein response, HSF1, DAF-16, Caenorhabditis elegans
MeSH terms
Aging, Animals, Gene Amplification, Protein Conformation, Caenorhabditis elegans, Protein Folding, Caenorhabditis elegans Proteins

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