Progeroid syndromes such as Hutchinson Gilford Progeroid syndrome (HGPS), Werner syndrome (WS) and Cockayne syndrome (CS), result in severely reduced lifespans and premature ageing. Normal senescent cells show splicing factor dysregulation, which has not yet been investigated in syndromic senescent cells. We sought to investigate the senescence characteristics and splicing factor expression profiles of progeroid dermal fibroblasts. Natural cellular senescence can be reversed by application of the senomorphic drug, trametinib, so we also investigated its ability to reverse senescence characteristics in syndromic cells. We found that progeroid cultures had a higher senescence burden, but did not always have differences in levels of proliferation, DNA damage repair and apoptosis. Splicing factor gene expression appeared dysregulated across the three syndromes. 10 µM trametinib reduced senescent cell load and affected other aspects of the senescence phenotype (including splicing factor expression) in HGPS and Cockayne syndromes. Werner syndrome cells did not demonstrate changes in in senescence following treatment. Splicing factor dysregulation in progeroid cells provides further evidence to support this mechanism as a hallmark of cellular ageing and highlights the use of progeroid syndrome cells in the research of ageing and age-related disease. This study suggests that senomorphic drugs such as trametinib could be a useful adjunct to therapy for progeroid diseases.

早衰综合征，例如Hutchinson Gilford早衰综合症（HGPS），Werner综合征（WS）和Cockayne综合征（CS），会导致寿命严重缩短和过早衰老。正常衰老细胞显示剪接因子失调，这尚未在综合征性衰老细胞中进行研究。我们试图研究早衰样真皮成纤维细胞的衰老特征和剪接因子表达谱。细胞自然衰老可以通过应用同形药物曲美替尼来逆转，因此我们还研究了其逆转综合征细胞衰老特性的能力。我们发现早衰样培养物具有较高的衰老负荷，但在增殖、DNA 损伤修复和细胞凋亡水平方面并不总是存在差异。剪接因子基因表达在 3 种综合征中表现失调。10 μM 曲美替尼降低衰老细胞载量并影响 HGPS 和 Cockayne 综合征中衰老表型的其他方面（包括剪接因子表达）。Werner 综合征细胞在治疗后未表现出衰老变化。早衰样细胞中的剪接因子失调提供了进一步的证据来支持这种机制是细胞衰老的标志，并强调了早衰综合征细胞在衰老和年龄相关疾病研究中的应用。这项研究表明，曲美替尼等异形药物可能是治疗早衰性疾病的有用辅助手段。