Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease
Aging and cellular senescence are increasingly recognized as key contributors to pulmonary fibrosis. However, our understanding in the context of scleroderma-associated interstitial lung disease (SSc-ILD) is limited. To investigate, we leveraged previously established lung aging- and cell-specific s...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1326922/full |
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| author | Monica M. Yang Seoyeon Lee Jessica Neely Monique Hinchcliff Paul J. Wolters Marina Sirota Marina Sirota |
| author_facet | Monica M. Yang Seoyeon Lee Jessica Neely Monique Hinchcliff Paul J. Wolters Marina Sirota Marina Sirota |
| author_sort | Monica M. Yang |
| collection | DOAJ |
| description | Aging and cellular senescence are increasingly recognized as key contributors to pulmonary fibrosis. However, our understanding in the context of scleroderma-associated interstitial lung disease (SSc-ILD) is limited. To investigate, we leveraged previously established lung aging- and cell-specific senescence signatures to determine their presence and potential relevance to SSc-ILD. We performed a gene expression meta-analysis of lung tissues from 38 SSc-ILD and 18 healthy controls and found that markers (GDF15, COMP, and CDKN2A) and pathways (p53) of senescence were significantly increased in SSc-ILD. When probing the established aging and cellular senescence signatures, we found that epithelial and fibroblast senescence signatures had a 3.6- and 3.7-fold enrichment, respectively, in the lung tissue of SSc-ILD and that lung aging genes (CDKN2A, FRZB, PDE1A, and NAPI12) were increased in SSc-ILD. These signatures were also enriched in SSc skin and associated with degree of skin involvement (limited vs. diffuse cutaneous). To further support these findings, we examined telomere length (TL), a surrogate for aging, in the lung tissue and found that, independent of age, SSc-ILD had significantly shorter telomeres than controls in type II alveolar cells in the lung. TL in SSc-ILD was comparable to idiopathic pulmonary fibrosis, a disease of known aberrant aging. Taken together, this study provides novel insight into the possible mechanistic effects of accelerated aging and aberrant cellular senescence in SSc-ILD pathogenesis. |
| first_indexed | 2024-03-08T10:01:55Z |
| format | Article |
| id | doaj.art-81d2ec4033a34889b3cbcd1af562f471 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T10:01:55Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-81d2ec4033a34889b3cbcd1af562f4712024-01-29T10:20:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011510.3389/fimmu.2024.13269221326922Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung diseaseMonica M. Yang0Seoyeon Lee1Jessica Neely2Monique Hinchcliff3Paul J. Wolters4Marina Sirota5Marina Sirota6Division of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, United StatesDivision of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, United StatesDivision of Pediatric Rheumatology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, United StatesDivision of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United StatesDivision of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA, United StatesBakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, United StatesAging and cellular senescence are increasingly recognized as key contributors to pulmonary fibrosis. However, our understanding in the context of scleroderma-associated interstitial lung disease (SSc-ILD) is limited. To investigate, we leveraged previously established lung aging- and cell-specific senescence signatures to determine their presence and potential relevance to SSc-ILD. We performed a gene expression meta-analysis of lung tissues from 38 SSc-ILD and 18 healthy controls and found that markers (GDF15, COMP, and CDKN2A) and pathways (p53) of senescence were significantly increased in SSc-ILD. When probing the established aging and cellular senescence signatures, we found that epithelial and fibroblast senescence signatures had a 3.6- and 3.7-fold enrichment, respectively, in the lung tissue of SSc-ILD and that lung aging genes (CDKN2A, FRZB, PDE1A, and NAPI12) were increased in SSc-ILD. These signatures were also enriched in SSc skin and associated with degree of skin involvement (limited vs. diffuse cutaneous). To further support these findings, we examined telomere length (TL), a surrogate for aging, in the lung tissue and found that, independent of age, SSc-ILD had significantly shorter telomeres than controls in type II alveolar cells in the lung. TL in SSc-ILD was comparable to idiopathic pulmonary fibrosis, a disease of known aberrant aging. Taken together, this study provides novel insight into the possible mechanistic effects of accelerated aging and aberrant cellular senescence in SSc-ILD pathogenesis.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1326922/fullsystemic sclerosisinterstitial lung diseaseagingcellular senescencegene expression |
| spellingShingle | Monica M. Yang Seoyeon Lee Jessica Neely Monique Hinchcliff Paul J. Wolters Marina Sirota Marina Sirota Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease Frontiers in Immunology systemic sclerosis interstitial lung disease aging cellular senescence gene expression |
| title | Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease |
| title_full | Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease |
| title_fullStr | Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease |
| title_full_unstemmed | Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease |
| title_short | Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease |
| title_sort | gene expression meta analysis reveals aging and cellular senescence signatures in scleroderma associated interstitial lung disease |
| topic | systemic sclerosis interstitial lung disease aging cellular senescence gene expression |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1326922/full |
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