Jeremian Richie, Galati Melissa, Fotovati Rayyan, Li Kaiyang, Jack Carolyn, Croitoru David O, Caucheteux Stephan, Lefrançois Philippe, Piguet Vincent
Division of Dermatology, Department of Medicine, McGill University, Montréal, Canada.
Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.
JID Innov. 2025 May 30;5(5):100386. doi: 10.1016/j.xjidi.2025.100386. eCollection 2025 Sep.
Epigenetic age acceleration has previously been observed in inflammatory skin disease; however, less is known regarding recently described age-related gene expression patterns ("transcriptional clocks"). We investigated the role of transcriptional clocks in patients with hidradenitis suppurativa (n = 37), those with atopic dermatitis (n = 27), those with plaque psoriasis (n = 28), and healthy subjects (n = 38) using 7 clock algorithms, to improve the understanding of underlying pathophysiology and disease trajectory. Five of 7 transcriptional clocks demonstrated moderate-to-strong accuracy in predicting age across groups (patients with atopic dermatitis: = 0.40-0.86, those with hidradenitis suppurativa: = 0.46-0.74, those with plaque psoriasis: = 0.50-0.80, healthy subjects: = 0.32-0.60; < .05). Age acceleration was observed in lesional versus healthy (patients with atopic dermatitis: +3.9∼9.8y, 2.8∼5.9; those with hidradenitis suppurativa: +5.0∼6.1y, = 2.5∼4.1; those with plaque psoriasis: +6.5∼12.5y, = 5.1∼8.0; < .05) and in lesional versus nonlesional skin in all diseases and less frequently observed in nonlesional versus healthy skin. In atopic dermatitis, loss-of-function sequence variants in the FLG gene were associated with transcriptional age acceleration, including dual carrier status ( = 2.3, < .05) and carrier status ( = 2.6, < .05). Pathway enrichment analyses revealed that clock genes are enriched in signatures related to aging, inflammation, and metabolism. Our study provides evidence for transcriptional age acceleration in inflammatory skin disease and sets a foundation for further investigation into the role of age-related transcriptional changes in the pathophysiology of these diseases.
此前在炎症性皮肤病中已观察到表观遗传年龄加速现象；然而，对于最近描述的与年龄相关的基因表达模式（“转录时钟”），我们了解得较少。我们使用7种时钟算法，对化脓性汗腺炎患者（n = 37）、特应性皮炎患者（n = 27）、斑块状银屑病患者（n = 28）和健康受试者（n = 38）进行了研究，以增进对潜在病理生理学和疾病发展轨迹的理解。7种转录时钟中有5种在预测各组年龄方面表现出中度到高度的准确性（特应性皮炎患者： = 0.40 - 0.86，化脓性汗腺炎患者： = 0.46 - 0.74，斑块状银屑病患者： = 0.50 - 0.80，健康受试者： = 0.32 - 0.60； <.05）。在所有疾病中，病变皮肤与健康皮肤相比均观察到年龄加速现象（特应性皮炎患者： +3.9∼9.8岁， = 2.8∼5.9；化脓性汗腺炎患者： +5.0∼6.1岁， = 2.5∼4.1；斑块状银屑病患者： +6.5∼12.5岁， = 5.1∼8.0； <.05），且病变皮肤与非病变皮肤相比也观察到年龄加速现象，而非病变皮肤与健康皮肤相比则较少观察到。在特应性皮炎中，FLG基因的功能丧失序列变异与转录年龄加速相关，包括双携带者状态（ = 2.3， <.05）和携带者状态（ = 2.6， <.05）。通路富集分析表明，时钟基因在与衰老、炎症和代谢相关的特征中富集。我们的研究为炎症性皮肤病中的转录年龄加速提供了证据，并为进一步研究与年龄相关的转录变化在这些疾病病理生理学中的作用奠定了基础。
