{"id":99587,"date":"2019-12-11T03:01:25","date_gmt":"2019-12-11T11:01:25","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2019\/12\/deficiency-in-the-dna-repair-protein-ercc1-triggers-a-link-between-senescence-and-apoptosis-in-human-fibroblasts-and-mouse-skin"},"modified":"2019-12-11T03:51:56","modified_gmt":"2019-12-11T11:51:56","slug":"deficiency-in-the-dna-repair-protein-ercc1-triggers-a-link-between-senescence-and-apoptosis-in-human-fibroblasts-and-mouse-skin","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2019\/12\/deficiency-in-the-dna-repair-protein-ercc1-triggers-a-link-between-senescence-and-apoptosis-in-human-fibroblasts-and-mouse-skin","title":{"rendered":"Deficiency in the DNA repair protein ERCC1 triggers a link between senescence and apoptosis in human fibroblasts and mouse skin"},"content":{"rendered":"<p style=\"padding-right: 20px\"><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/deficiency-in-the-dna-repair-protein-ercc1-triggers-a-link-between-senescence-and-apoptosis-in-human-fibroblasts-and-mouse-skin5.jpg\"><\/a><\/p>\n<p>ERCC1 (excision repair cross complementing\u2010group 1) is a mammalian endonuclease that incises the damaged strand of DNA during nucleotide excision repair and interstrand cross\u2010link repair. <i>Ercc1<sup>\u2212\/\u0394<\/sup><\/i> mice, carrying one null and one hypomorphic <i>Ercc1<\/i> allele, have been widely used to study aging due to accelerated aging phenotypes in numerous organs and their shortened lifespan. <i>Ercc1<sup>\u2212\/\u0394<\/sup><\/i> mice display combined features of human progeroid and cancer\u2010prone syndromes. Although several studies report cellular senescence and apoptosis associated with the premature aging of <i>Ercc1<sup>\u2212\/\u0394<\/sup><\/i> mice, the link between these two processes and their physiological relevance in the phenotypes of <i>Ercc1<sup>\u2212\/\u0394<\/sup><\/i> mice are incompletely understood. Here, we show that ERCC1 depletion, both in cultured human fibroblasts and the skin of <i>Ercc1<sup>\u2212\/\u0394<\/sup><\/i> mice, initially induces cellular senescence and, importantly, increased expression of several SASP (senescence\u2010associated secretory phenotype) factors. Cellular senescence induced by ERCC1 deficiency was dependent on activity of the p53 tumor\u2010suppressor protein. In turn, TNF\u03b1 secreted by senescent cells induced apoptosis, not only in neighboring ERCC1\u2010deficient nonsenescent cells, but also cell autonomously in the senescent cells themselves. In addition, expression of the stem cell markers p63 and Lgr6 was significantly decreased in <i>Ercc1<sup>\u2212\/\u0394<\/sup><\/i> mouse skin, where the apoptotic cells are localized, compared to age\u2010matched wild\u2010type skin, possibly due to the apoptosis of stem cells. These data suggest that ERCC1\u2010depleted cells become susceptible to apoptosis via TNF\u03b1 secreted from neighboring senescent cells. We speculate that parts of the premature aging phenotypes and shortened health\u2010 or lifespan may be due to stem cell depletion through apoptosis promoted by senescent cells.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>ERCC1 (excision repair cross complementing\u2010group 1) is a mammalian endonuclease that incises the damaged strand of DNA during nucleotide excision repair and interstrand cross\u2010link repair. Ercc1\u2212\/\u0394 mice, carrying one null and one hypomorphic Ercc1 allele, have been widely used to study aging due to accelerated aging phenotypes in numerous organs and their shortened lifespan. Ercc1\u2212\/\u0394 [\u2026]<\/p>\n","protected":false},"author":511,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,269,6],"tags":[],"class_list":["post-99587","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-life-extension","category-robotics-ai"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/99587","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/511"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=99587"}],"version-history":[{"count":1,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/99587\/revisions"}],"predecessor-version":[{"id":99606,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/99587\/revisions\/99606"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=99587"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=99587"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=99587"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}