Institute of Biomedicine - iBiMED, Department of Health Sciences, University of Aveiro, Aveiro, Portugal.
Institute of Biomedicine - iBiMED, Department of Health Sciences, University of Aveiro, Aveiro, Portugal.
Ageing Res Rev. 2020 Sep;62:101119. doi: 10.1016/j.arr.2020.101119. Epub 2020 Jun 27.
Protein aggregation is a phenomenon of major relevance in neurodegenerative and neuromuscular disorders, cataracts, diabetes and many other diseases. Research has unveiled that proteins also aggregate in multiple tissues during healthy aging yet, the biological and biomedical relevance of this apparently asymptomatic phenomenon remains to be understood. It is known that proteome homeostasis (proteostasis) is maintained by a balanced protein synthesis rate, high protein synthesis accuracy, efficient protein folding and continual tagging of damaged proteins for degradation, suggesting that protein aggregation during healthy aging may be associated with alterations in both protein synthesis and the proteostasis network (PN) pathways. In particular, dysregulation of protein synthesis and alterations in translation fidelity are hypothesized to lead to the production of misfolded proteins which could explain the occurrence of age-related protein aggregation. Nevertheless, some data on this topic is controversial and the biological mechanisms that lead to widespread protein aggregation remain to be elucidated. We review the recent literature about the age-related decline of proteostasis, highlighting the need to build an integrated view of protein synthesis rate, fidelity and quality control pathways in order to better understand the proteome alterations that occur during aging and in age-related diseases.
蛋白质聚集是神经退行性和神经肌肉疾病、白内障、糖尿病和许多其他疾病的主要相关现象。研究表明，在健康衰老过程中，蛋白质也会在多种组织中聚集，但这一显然无症状的现象的生物学和生物医学意义仍有待理解。已知蛋白质组平衡（蛋白质稳态）是通过平衡的蛋白质合成率、高蛋白质合成准确性、有效的蛋白质折叠和持续标记受损蛋白质进行降解来维持的，这表明健康衰老过程中的蛋白质聚集可能与蛋白质合成和蛋白质稳态网络（PN）途径的改变有关。特别是，蛋白质合成的失调和翻译保真度的改变被假设导致错误折叠的蛋白质的产生，这可以解释与年龄相关的蛋白质聚集的发生。然而，关于这个主题的一些数据存在争议，导致广泛蛋白质聚集的生物学机制仍有待阐明。我们回顾了最近关于蛋白质稳态与年龄相关下降的文献，强调需要建立一个综合的蛋白质合成率、保真度和质量控制途径的观点，以便更好地理解衰老过程中和与年龄相关的疾病中发生的蛋白质组改变。
