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

Domenico Di Fraia, Antonio Marino, Jae Ho Lee, Erika Kelmer Sacramento, Mario Baumgart, Sara Bagnoli, Till Balla, Felix Schalk, Stephan Kamrad, Rui Guan, Cinzia Caterino, Chiara Giannuzzi, Pedro Tomaz da Silva, Amit Kumar Sahu, Hanna Gut, Giacomo Siano, Max Tiessen, Eva Terzibasi-Tozzini, Eugenio F Fornasiero, Julien Gagneur, Christoph Englert, Kiran R Patil, Clara Correia-Melo, Danny D Nedialkova, Judith Frydman, Alessandro Cellerino, Alessandro Ori

Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena, Germany. · pubmed

Paper

Abstract

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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Research summary

The paper claims that altered translation elongation contributes to key hallmarks of aging in the killifish brain. This research addresses fundamental biological processes related to aging and identifies potential vulnerabilities in the aging brain, which could lead to insights into the root causes of aging and age-related diseases.

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