Lamin A, a main constituent of the nuclear lamina, is the major splicing product of the LMNA gene, which also encodes lamin C, lamin A delta 10 and lamin C2. Involvement of lamin A in the ageing process became clear after the discovery that a group of progeroid syndromes, currently referred to as progeroid laminopathies, are caused by mutations in LMNA gene. Progeroid laminopathies include Hutchinson-Gilford Progeria, Mandibuloacral Dysplasia, Atypical Progeria and atypical-Werner syndrome, disabling and life-threatening diseases with accelerated ageing, bone resorption, lipodystrophy, skin abnormalities and cardiovascular disorders. Defects in lamin A post-translational maturation occur in progeroid syndromes and accumulated prelamin A affects ageing-related processes, such as mTOR signaling, epigenetic modifications, stress response, inflammation, microRNA activation and mechanosignaling. In this review, we briefly describe the role of these pathways in physiological ageing and go in deep into lamin A-dependent mechanisms that accelerate the ageing process. Finally, we propose that lamin A acts as a sensor of cell intrinsic and environmental stress through transient prelamin A accumulation, which triggers stress response mechanisms. Exacerbation of lamin A sensor activity due to stably elevated prelamin A levels contributes to the onset of a permanent stress response condition, which triggers accelerated ageing.

核纤层蛋白的主要成分Lamin A是LMNA基因的主要剪接产物，它还编码lamin C，lamin A delta 10和lamin C2。在发现一组早衰综合症（目前称为早衰症）是由LMNA突变引起的后，Lamin A参与了衰老过程基因。早衰症的拉丁病包括Hutchinson-Gilford早衰症，下颌骨发育不良，非典型性早衰症和非典型性Werner综合征，衰老和威胁生命的疾病，其中包括加速衰老，骨骼吸收，脂肪营养不良，皮肤异常和心血管疾病。核纤层蛋白A翻译后成熟中的缺陷发生在progeroid综合征中，并且累积的prelamin A影响与衰老相关的过程，例如mTOR信号传导，表观遗传修饰，应激反应，炎症，microRNA激活和机械信号转导。在这篇综述中，我们简要描述了这些途径在生理衰老中的作用，并深入研究了层状A依赖性机制，这些机制加速了衰老过程。最后，我们建议lamin A通过短暂的prelamin A积累，充当细胞内在和环境压力的传感器，触发压力反应机制。稳定升高的prelamin A水平会导致lamin A传感器活动加剧，从而导致永久性应激反应状态的发生，从而加速衰老。