Alternative splicing in aging and longevity.
Alternative splicing in aging and longevity.
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DOI：
10.1007/s00439-019-02094-6
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发表时间：
2020-03
期刊：
影响因子：
5.3
通讯作者：
Mair WB
中科院分区：
文献类型：
--
作者：
Bhadra M;Howell P;Dutta S;Heintz C;Mair WB
可选的前mrna剪接增加了可用基因组编码序列产生的蛋白质组的复杂性。剪接过程的失调与许多疾病有关。然而，剪接最近与衰老过程本身和促进长寿的干预措施联系在一起。本文综述了近年来将RNA剪接定义为衰老新标志的研究进展。我们强调了导致多个物种衰老表型的功能失调的选择性剪接事件，以及最近在破译RNA剪接在衰老和长寿调节中的机制作用方面的努力。此外，我们讨论了最近的研究表明，在促进长寿的干预措施中，特定剪接因子是直接需要的，特别是营养信号通路如何与剪接因子调节和下游剪接靶点相结合。最后，我们回顾了使用剪接谱作为生物年龄和预期寿命预测因子的新兴潜力。了解RNA剪接成分和下游靶点在衰老过程中的作用，可能为开发治疗方法提供机会，并最终延长人类的健康寿命。
Alternative pre-mRNA splicing increases the complexity of the proteome that can be generated from the available genomic coding sequences. Dysregulation of the splicing process has been implicated in a vast repertoire of diseases. However, splicing has recently been linked to both the aging process itself and pro-longevity interventions. This review focuses on recent research towards defining RNA splicing as a new hallmark of aging. We highlight dysfunctional alternative splicing events that contribute to the aging phenotype across multiple species, along with recent efforts toward deciphering mechanistic roles for RNA splicing in the regulation of aging and longevity. Further, we discuss recent research demonstrating a direct requirement for specific splicing factors in pro-longevity interventions, and specifically how nutrient signaling pathways interface to splicing factor regulation and downstream splicing targets. Lastly, we review the emerging potential of using splicing profiles as a predictor of biological age and life expectancy. Understanding the role of RNA splicing components and downstream targets altered in aging may provide opportunities to develop therapeutics and ultimately extend healthy lifespan in humans.
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