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Proteostasis and the Aging Proteome in Health and Disease
Open accessAbstract
The maintenance of the proteome is essential to preserve cell functionality and the ability to respond and adapt to the changing environment. This is regulated by the proteostasis network, a dedicated set of molecular components comprised of molecular chaperones and protein clearance mechanisms, regulated by cell stress signaling pathways, that prevents the toxicity associated with protein misfolding and accumulation of toxic aggregates in different subcellular compartments and tissues. The efficiency of the proteostasis network declines with age and this failure in protein homeostasis has been proposed to underlie the basis of common age-related human disorders. The current advances in the understanding of the mechanisms and regulation of proteostasis and of the different types of digressions in this process in aging have turned the attention toward the therapeutic opportunities offered by the restoration of proteostasis in age-associated degenerative diseases. Here, we discuss some of the unresolved questions on proteostasis that need to be addressed to enhance healthspan and to diminish the pathology associated with persistent protein damage.
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“aging is associated with impaired activity of the proteasome and mitochondrial Lon proteases [203,204,205] and reduced capacity for macromolecule repair [201,202].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [205]
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Metadata
- Authors
- Morimoto, R. I., & Cuervo, A. M.
- Affiliations
- Northwestern University (US)
- Albert Einstein College of Medicine (US)
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-05-14
- Volume
- 69
- Issue
- Suppl 1
- Pages
- S33-S38
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC4022129
- OpenAlex
- W2136597136
- Cited by
- 277
- References
- 33
- Citations by year
- 2026: 15 · 2025: 19 · 2024: 14 · 2023: 24 · 2022: 19 · 2021: 25 · 2020: 24 · 2019: 26 · 2018: 25 · 2017: 30 · 2016: 20 · 2015: 26 · 2014: 9
- FWCI
- 11.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG 026647, P01AG031782, AG031782, AG21904)
- National Institute of General Medical Sciences (GM081192, GM 038109)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK090408)
- National Institute of Neurological Disorders and Stroke (NS038370, NS-047331, P50NS038370, R01NS047331)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- proteostasis, molecular chaperones, protein misfolding, protein aggregates, age-related diseases, degenerative diseases, healthspan, stress signaling pathways
- MeSH terms
- Aging, Chronic Disease, Homeostasis, Humans, Signal Transduction, Protein Folding, Molecular Chaperones, Proteome
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