Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
Department of Drug Sciences, Section of Pharmacology, University of Pavia, Pavia, Italy.
Ageing Res Rev. 2023 Jul;88:101958. doi: 10.1016/j.arr.2023.101958. Epub 2023 May 19.
Aging represents the major risk factor for the onset and/or progression of various disorders including neurodegenerative diseases, metabolic disorders, and bone-related defects. As the average age of the population is predicted to exponentially increase in the coming years, understanding the molecular mechanisms underlying the development of aging-related diseases and the discovery of new therapeutic approaches remain pivotal. Well-reported hallmarks of aging are cellular senescence, genome instability, autophagy impairment, mitochondria dysfunction, dysbiosis, telomere attrition, metabolic dysregulation, epigenetic alterations, low-grade chronic inflammation, stem cell exhaustion, altered cell-to-cell communication and impaired proteostasis. With few exceptions, however, many of the molecular players implicated within these processes as well as their role in disease development remain largely unknown. RNA binding proteins (RBPs) are known to regulate gene expression by dictating at post-transcriptional level the fate of nascent transcripts. Their activity ranges from directing primary mRNA maturation and trafficking to modulation of transcript stability and/or translation. Accumulating evidence has shown that RBPs are emerging as key regulators of aging and aging-related diseases, with the potential to become new diagnostic and therapeutic tools to prevent or delay aging processes. In this review, we summarize the role of RBPs in promoting cellular senescence and we highlight their dysregulation in the pathogenesis and progression of the main aging-related diseases, with the aim of encouraging further investigations that will help to better disclose this novel and captivating molecular scenario.
衰老是多种疾病（包括神经退行性疾病、代谢紊乱和骨骼相关缺陷）发病和/或进展的主要危险因素。由于预计未来几年人口平均年龄将呈指数级增长，因此了解与衰老相关疾病发展相关的分子机制以及发现新的治疗方法仍然至关重要。衰老的公认特征包括细胞衰老、基因组不稳定性、自噬损伤、线粒体功能障碍、微生态失调、端粒磨损、代谢失调、表观遗传改变、低度慢性炎症、干细胞衰竭、细胞间通讯改变和蛋白质稳态受损。然而，除了少数例外，这些过程中涉及的许多分子参与者及其在疾病发展中的作用在很大程度上仍然未知。RNA 结合蛋白 (RBP) 通过在转录后水平决定新生转录本的命运来调节基因表达。它们的活性范围从指导初级 mRNA 成熟和运输到调节转录本稳定性和/或翻译。越来越多的证据表明，RBP 是衰老和与衰老相关疾病的关键调节剂，有可能成为新的诊断和治疗工具，以预防或延缓衰老过程。在这篇综述中，我们总结了 RBP 在促进细胞衰老中的作用，并强调了它们在主要与衰老相关疾病的发病机制和进展中的失调，目的是鼓励进一步的研究，以帮助更好地揭示这一新颖而迷人的分子情景。
