Investigating Transcriptional Age Acceleration in Inflammatory Skin Diseases
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...
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Elsevier
2025-09-01
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| Series: | JID Innovations |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667026725000426 |
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| author | Richie Jeremian Melissa Galati Rayyan Fotovati Kaiyang Li Carolyn Jack David O. Croitoru Stephan Caucheteux Philippe Lefrançois Vincent Piguet |
| author_facet | Richie Jeremian Melissa Galati Rayyan Fotovati Kaiyang Li Carolyn Jack David O. Croitoru Stephan Caucheteux Philippe Lefrançois Vincent Piguet |
| author_sort | Richie Jeremian |
| collection | DOAJ |
| description | 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: ρ = 0.40–0.86, those with hidradenitis suppurativa: ρ = 0.46–0.74, those with plaque psoriasis: ρ = 0.50–0.80, healthy subjects: ρ = 0.32–0.60; P < .05). Age acceleration was observed in lesional versus healthy (patients with atopic dermatitis: +3.9∼9.8y, t = 2.8∼5.9; those with hidradenitis suppurativa: +5.0∼6.1y, t = 2.5∼4.1; those with plaque psoriasis: +6.5∼12.5y, t = 5.1∼8.0; P < .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 FLGR244X/2282del4 dual carrier status (t = 2.3, P < .05) and FLGR501X carrier status (t = 2.6, P < .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. |
| format | Article |
| id | doaj-art-896ccca56e6b44c9ab5e29873b5e7e5b |
| institution | Matheson Library |
| issn | 2667-0267 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JID Innovations |
| spelling | doaj-art-896ccca56e6b44c9ab5e29873b5e7e5b2025-07-19T04:39:23ZengElsevierJID Innovations2667-02672025-09-0155100386Investigating Transcriptional Age Acceleration in Inflammatory Skin DiseasesRichie Jeremian0Melissa Galati1Rayyan Fotovati2Kaiyang Li3Carolyn Jack4David O. Croitoru5Stephan Caucheteux6Philippe Lefrançois7Vincent Piguet8Division of Dermatology, Department of Medicine, McGill University, Montréal, CanadaTemerty Faculty of Medicine, University of Toronto, Toronto, CanadaFaculty of Medicine and Health Sciences, McGill University, Montréal, CanadaFaculty of Medicine and Health Sciences, McGill University, Montréal, CanadaDivision of Dermatology, Department of Medicine, McGill University, Montréal, CanadaDivision of Dermatology, Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, CanadaDivision of Dermatology, Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, CanadaLady Davis Institute (LDI), Jewish General Hospital, Montréal, CanadaDivision of Dermatology, Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada; Division of Dermatology, Department of Medicine, Women’s College Hospital, Toronto, Canada; Correspondence: Vincent Piguet, Division of Dermatology, Department of Medicine, Temerty Faculty of Medicine, University of Toronto, 76 Grenville Street, Office 6425, Toronto M5S 1B2, Canada.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: ρ = 0.40–0.86, those with hidradenitis suppurativa: ρ = 0.46–0.74, those with plaque psoriasis: ρ = 0.50–0.80, healthy subjects: ρ = 0.32–0.60; P < .05). Age acceleration was observed in lesional versus healthy (patients with atopic dermatitis: +3.9∼9.8y, t = 2.8∼5.9; those with hidradenitis suppurativa: +5.0∼6.1y, t = 2.5∼4.1; those with plaque psoriasis: +6.5∼12.5y, t = 5.1∼8.0; P < .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 FLGR244X/2282del4 dual carrier status (t = 2.3, P < .05) and FLGR501X carrier status (t = 2.6, P < .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.http://www.sciencedirect.com/science/article/pii/S2667026725000426AgingAtopic dermatitisHidradenitis suppurativaPsoriasisRNA-seq |
| spellingShingle | Richie Jeremian Melissa Galati Rayyan Fotovati Kaiyang Li Carolyn Jack David O. Croitoru Stephan Caucheteux Philippe Lefrançois Vincent Piguet Investigating Transcriptional Age Acceleration in Inflammatory Skin Diseases JID Innovations Aging Atopic dermatitis Hidradenitis suppurativa Psoriasis RNA-seq |
| title | Investigating Transcriptional Age Acceleration in Inflammatory Skin Diseases |
| title_full | Investigating Transcriptional Age Acceleration in Inflammatory Skin Diseases |
| title_fullStr | Investigating Transcriptional Age Acceleration in Inflammatory Skin Diseases |
| title_full_unstemmed | Investigating Transcriptional Age Acceleration in Inflammatory Skin Diseases |
| title_short | Investigating Transcriptional Age Acceleration in Inflammatory Skin Diseases |
| title_sort | investigating transcriptional age acceleration in inflammatory skin diseases |
| topic | Aging Atopic dermatitis Hidradenitis suppurativa Psoriasis RNA-seq |
| url | http://www.sciencedirect.com/science/article/pii/S2667026725000426 |
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