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Di Fraia, D.* ; Marino, A.* ; Lee, J.H.* ; Kelmer Sacramento, E.* ; Baumgart, M.* ; Bagnoli, S.* ; Balla, T.* ; Schalk, F.* ; Kamrad, S.* ; Guan, R.* ; Caterino, C.* ; Giannuzzi, C.* ; Tomaz da Silva, P.* ; Sahu, A.K.* ; Gut, H.* ; Siano, G.* ; Tiessen, M.* ; Terzibasi-Tozzini, E.* ; Fornasiero, E.F.* ; Gagneur, J. ; Englert, C.* ; Patil, K.R.* ; Correia-Melo, C.* ; Nedialkova, D.D.* ; Frydman, J.* ; Cellerino, A.* ; Ori, A.*

Altered translation elongation contributes to key hallmarks of aging in the killifish brain.

Science 389:eadk3079 (2025)
Postprint Research data DOI PMC
Open Access Green
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
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 0036-8075
e-ISSN 1095-9203
Journal Science
Quellenangaben Volume: 389, Issue: 6759, Pages: , Article Number: eadk3079 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place 1200 New York Ave, Nw, Washington, Dc 20005 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503800-001
Grants German Research Council
DOI 10.1126/science.adk3079
WOS ID 001550635200012
Scopus ID 105013153058
PubMed ID 40743332
Erfassungsdatum 2025-08-01
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