Proteins are molecular machines that provide structure and perform vital transport, signalling and enzymatic roles. Proteins expressed by cells require tight regulation of their concentration, folding, localisation, and modifications; however, this state of protein homeostasis is continuously perturbed by tissue-level stresses. While cells in healthy tissues are able to buffer against these perturbations, for example, by expression of chaperone proteins, protein homeostasis is lost in ageing, and can lead to protein aggregation characteristic of protein folding diseases. Here, we review reports of a progressive disconnect between transcriptomic and proteomic regulation during cellular ageing. We discuss how age-associated changes to cellular responses to specific stressors in the tissue microenvironment are exacerbated by loss of ribosomal proteins, ribosomal pausing, and mistranslation.

蛋白质是提供结构并发挥重要运输、信号传导和酶作用的分子机器。细胞表达的蛋白质需要对其浓度、折叠、定位和修饰进行严格调节；然而，这种蛋白质稳态不断受到组织水平压力的干扰。虽然健康组织中的细胞能够缓冲这些扰动，例如通过伴侣蛋白的表达，但蛋白质稳态在衰老过程中会丧失，并可能导致蛋白质折叠疾病的蛋白质聚集特征。在这里，我们回顾了细胞衰老过程中转录组和蛋白质组调节之间逐渐脱节的报道。我们讨论了核糖体蛋白的丢失、核糖体暂停和误译如何加剧细胞对组织微环境中特定应激源的反应的与年龄相关的变化。