Department of Neuro- and Sensory Physiology, University Medical Center Göttingen, 37073 Göttingen, Germany.
Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, 07743 Jena, Germany.
Nucleic Acids Res. 2024 Apr 12;52(6):2865-2885. doi: 10.1093/nar/gkae172.
A comprehensive understanding of molecular changes during brain aging is essential to mitigate cognitive decline and delay neurodegenerative diseases. The interpretation of mRNA alterations during brain aging is influenced by the health and age of the animal cohorts studied. Here, we carefully consider these factors and provide an in-depth investigation of mRNA splicing and dynamics in the aging mouse brain, combining short- and long-read sequencing technologies with extensive bioinformatic analyses. Our findings encompass a spectrum of age-related changes, including differences in isoform usage, decreased mRNA dynamics and a module showing increased expression of neuronal genes. Notably, our results indicate a reduced abundance of mRNA isoforms leading to nonsense-mediated RNA decay and suggest a regulatory role for RNA-binding proteins, indicating that their regulation may be altered leading to the reshaping of the aged brain transcriptome. Collectively, our study highlights the importance of studying mRNA splicing events during brain aging.
全面了解大脑衰老过程中的分子变化对于减轻认知能力下降和延缓神经退行性疾病至关重要。在大脑衰老过程中，mRNA 变化的解释受到所研究动物群体的健康和年龄的影响。在这里，我们仔细考虑了这些因素，并结合短读和长读测序技术以及广泛的生物信息学分析，对衰老小鼠大脑中的 mRNA 剪接和动态进行了深入研究。我们的研究结果涵盖了一系列与年龄相关的变化，包括异构体使用的差异、mRNA 动态的减少以及一个模块显示神经元基因表达增加。值得注意的是，我们的结果表明，mRNA 异构体的丰度降低导致无意义介导的 RNA 衰变，并表明 RNA 结合蛋白的调节作用，表明它们的调节可能发生改变，导致衰老大脑转录组的重塑。总的来说，我们的研究强调了在大脑衰老过程中研究 mRNA 剪接事件的重要性。
