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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 Forschungsdaten 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Complex-i; Rna; Protein; Transcriptome; Identification; Activation; Resolution; Proteomics; Stability; Modifier
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 0036-8075
e-ISSN 1095-9203
Zeitschrift Science
Quellenangaben Band: 389, Heft: 6759, Seiten: , Artikelnummer: eadk3079 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort 1200 New York Ave, Nw, Washington, Dc 20005 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-503800-001
Förderungen 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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