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Increased cellular senescence (SEN) and oxidative stress in trisomies have gained recent attention. We assessed SEN, SEN-associated secretory phenotype (SASP), and oxidative stress on trisomy 13 (T13), T18, and T21 human fetal lung tissues and isolated primary human fetal lung fibroblasts. Telomerase-associated foci staining showed DNA damage primarily within T21 and T18 lungs. These results were confirmed by real-time quantitative PCR showing an increase of the SEN marker CDKN2B and SASP markers IL-6 and CXCL8. In contrast, lung tissues from T13 showed an upregulation of CDKN2A, whereas no significant changes in SASP marker genes were observed. \u03b3-H2AX (H2A histone family member X) was upregulated in each genotype, particularly in T21. Isolated fibroblasts demonstrated a strong association between T21 and several SEN markers. An increase of \u03b3-H2AX\u2013positive cells were observed in fibroblasts from T21, T18, and T13, but only T21 exhibited an increase in P21 expression. Only T21 fibroblasts displayed a significant increase in reactive oxygen species levels, as indicated by MitoSOX and CellROX. This study provides the first evidence of a link between SEN and trisomy anomalies during prenatal human lung development, particularly in T21.<\/jats:p>","DOI":"10.1165\/rcmb.2024-0361oc","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T12:42:33Z","timestamp":1740746553000},"page":"251-263","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":5,"title":["Elevated Senescence Markers in Developing Trisomy 21 Human Lungs"],"prefix":"10.1093","volume":"73","author":[{"given":"Randa","family":"Belgacemi","sequence":"first","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Harbor\u2013UCLA Medical Center, Torrance, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Cherry","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Harbor\u2013UCLA Medical Center, Torrance, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maunick","family":"Koloko Ngassie","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Rehan","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Harbor\u2013UCLA Medical Center, Torrance, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imad","family":"El Alam","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Harbor\u2013UCLA Medical Center, Torrance, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Jourdan Le Saux","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Glass","sequence":"additional","affiliation":[{"name":"University of Washington School of Medicine, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0027-9545","authenticated-orcid":false,"suffix":"Jr.","given":"Rodney D.","family":"Britt","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research, Nationwide Children\u2019s Hospital, Columbus, Ohio; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. 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