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Altered translation elongation contributes to key hallmarks of aging in the killifish brain.
Science 389, 22:eadk3079 (2025)
Aging is a major risk factor for neurodegeneration and is characterized by diverse cellular and molecular hallmarks. To understand the origin of these hallmarks, we studied the effects of aging on the transcriptome, translatome, and proteome in the brain of short-lived killifish. We identified a cascade of events in which aberrant translation pausing led to altered abundance of proteins independently of transcriptional regulation. In particular, aging caused increased ribosome stalling and widespread depletion of proteins enriched in basic amino acids. These findings uncover a potential vulnerable point in the aging brain's biology-the biogenesis of basic DNA and RNA binding proteins. This vulnerability may represent a unifying principle that connects various aging hallmarks, encompassing genome integrity, proteostasis, and the biosynthesis of macromolecules.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Complex-i; Rna; Protein; Transcriptome; Identification; Activation; Resolution; Proteomics; Stability; Modifier
ISSN (print) / ISBN
0036-8075
e-ISSN
1095-9203
Journal
Science
Quellenangaben
Volume: 389,
Issue: 6759,
Pages: 22,
Article Number: eadk3079
Publisher
American Association for the Advancement of Science (AAAS)
Publishing Place
1200 New York Ave, Nw, Washington, Dc 20005 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Computational Biology (ICB)
Grants
German Research Council