{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:28:08Z","timestamp":1790843288081,"version":"4.1.0"},"reference-count":138,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cockayne Syndrome (CS) is an autosomal recessive disorder arising from mutations in either of two disease\u2010associated genes,\n                    <jats:italic>ERCC6 or ERCC8<\/jats:italic>\n                    . CS patients exhibit cutaneous photosensitivity, neuropathological abnormalities, severe growth retardation, a distinctive facial appearance with pronounced sunken eyes, musculoskeletal anomalies, sensory impairment, and dental decay. Approximately 70% of all CS cases carry\n                    <jats:italic>ERCC6<\/jats:italic>\n                    mutations; therefore, this review will focus solely on Cockayne Syndrome complementation group B (CS\u2010B). CS\u2010B exhibits several hallmarks of aging, including genomic instability, epigenetic modifications, loss of proteostasis, and mitochondrial failure. CS\u2010B is proposed to result from the accumulation of DNA damage and the resulting transcription impairment. However, the main pathophysiological mechanisms underlying the severe cellular impairments observed in CS\u2010B remain unclear. Here, we review the current literature to elucidate ERCC6\u2010related mechanisms, highlighting the key and emerging pathological mechanisms underlying CS\u2010B, as well as their putative interactions. Considering the mechanisms that heavily rely on ERCC6, we propose that CS\u2010B pathogenesis arises from a combination of DNA damage accumulation, transcriptional dysregulation, and mitochondrial dysfunction. Furthermore, we argue that these molecular features influence each other, rather than acting as isolated mechanisms. This suggests that the crosstalk between mechanisms is a key factor for CS\u2010B pathogenesis. Although efforts have been made to unveil CS\u2010B pathogenesis, research is still lacking, hindering progress in understanding this deadly disease. Future work will prove crucial to determine the main contributor to CS\u2010B pathogenesis and identify new interactions between CS\u2010B\u2010affected mechanisms.\n                  <\/jats:p>","DOI":"10.1111\/acel.70136","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T06:40:04Z","timestamp":1750315204000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Insights Into Cockayne Syndrome Type B: What Underlies Its Pathogenesis?"],"prefix":"10.1111","volume":"24","author":[{"given":"Ricardo","family":"Afonso\u2010Reis","sequence":"first","affiliation":[{"name":"ABC\u2010RI Algarve Biomedical Center Research Institute  Faro Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas Universidade do Algarve  Faro Portugal"},{"name":"Horae Gene Therapy Center UMass Chan Medical School  Worcester Massachusetts USA"},{"name":"Programa doutoral em Ci\u00eancias Biom\u00e9dicas Universidade do Algarve  Faro Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana R.","family":"Madeira","sequence":"additional","affiliation":[{"name":"ABC\u2010RI Algarve Biomedical Center Research Institute  Faro Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas Universidade do Algarve  Faro Portugal"},{"name":"Programa doutoral em Ci\u00eancias Biom\u00e9dicas Universidade do Algarve  Faro Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2726-9347","authenticated-orcid":false,"given":"David V. 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