Project description:Aging and neurodegeneration entail diverse cellular and molecular hallmarks. Here, we studied the effects of aging on the transcriptome, translatome, and multiple layers of the proteome in the brain of a short-lived killifish. We reveal that aging causes widespread reduction of proteins enriched in basic amino acids that is independent of mRNA regulation, and it is not due to impaired proteasome activity. Instead, we identify a cascade of events where aberrant translation pausing leads to reduced ribosome availability resulting in proteome remodeling independently of transcriptional regulation. Our research uncovers a vulnerable point in the aging brain's biology - the biogenesis of basic DNA/RNA binding proteins. This vulnerability may represent a unifying principle that connects various aging hallmarks, encompassing genome integrity and the biosynthesis of macromolecules.
Project description:Ribosome profiling on killifish brains coming from adult and old animals. Fractions have been pulled as described in the M&M and analysed by DIA proteomics.
Project description:Proteome DIA analysis of brain tissue from old (32 weeks old) killifish treated for 3 weeks with bortezomib to reduce the proteasome activity or DMSO as control.
Project description:In order to understand molecular basis of cardiac ageing in killifish, we have performed RNA Seq on the ventricular regions of young and aged killifish. Experiment was performed in biological triplicates.
Project description:Aging is a major risk factor for neurodegeneration and is characterized by diverse cellular and molecular hallmarks. To understand their origin, 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.
Project description:Aging is a major risk factor for neurodegeneration and is characterized by diverse cellular and molecular hallmarks. To understand their origin, 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.