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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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Complex-i; Rna; Protein; Transcriptome; Identification; Activation; Resolution; Proteomics; Stability; Modifier
ISSN (print) / ISBN
0036-8075
e-ISSN
1095-9203
Zeitschrift
Science
Quellenangaben
Band: 389,
Heft: 6759,
Seiten: 22,
Artikelnummer: eadk3079
Verlag
American Association for the Advancement of Science (AAAS)
Verlagsort
1200 New York Ave, Nw, Washington, Dc 20005 Usa
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Computational Biology (ICB)
Förderungen
German Research Council