{"id":97617,"date":"2019-10-19T22:03:03","date_gmt":"2019-10-20T05:03:03","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2019\/10\/downregulation-of-the-inflammatory-network-in-senescent-fibroblasts-and-aging-tissues-of-the-long%e2%80%90lived-and-cancer%e2%80%90resistant-subterranean-wild-rodent-spalax"},"modified":"2019-10-19T22:03:03","modified_gmt":"2019-10-20T05:03:03","slug":"downregulation-of-the-inflammatory-network-in-senescent-fibroblasts-and-aging-tissues-of-the-long%e2%80%90lived-and-cancer%e2%80%90resistant-subterranean-wild-rodent-spalax","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2019\/10\/downregulation-of-the-inflammatory-network-in-senescent-fibroblasts-and-aging-tissues-of-the-long%e2%80%90lived-and-cancer%e2%80%90resistant-subterranean-wild-rodent-spalax","title":{"rendered":"Downregulation of the inflammatory network in senescent fibroblasts and aging tissues of the long\u2010lived and cancer\u2010resistant subterranean wild rodent, Spalax"},"content":{"rendered":"<p><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/downregulation-of-the-inflammatory-network-in-senescent-fibroblasts-and-aging-tissues-of-the-longe28090lived-and-cancere28090resistant-subterranean-wild-rodent-spalax2.jpg\"><\/a><\/p>\n<p>The blind mole rat (<i>Spalax<\/i>) is a wild, long\u2010lived rodent that has evolved mechanisms to tolerate hypoxia and resist cancer. Previously, we demonstrated high DNA repair capacity and low DNA damage in <i>Spalax<\/i> fibroblasts following genotoxic stress compared with rats. Since the acquisition of senescence\u2010associated secretory phenotype (SASP) is a consequence of persistent DNA damage, we investigated whether cellular senescence in <i>Spalax<\/i> is accompanied by an inflammatory response. <i>Spalax<\/i> fibroblasts undergo replicative senescence (RS) and etoposide\u2010induced senescence (EIS), evidenced by an increased activity of senescence\u2010associated beta\u2010galactosidase (SA\u2010\u03b2\u2010Gal), growth arrest, and overexpression of p21, p16, and p53 mRNAs. Yet, unlike mouse and human fibroblasts, RS and EIS <i>Spalax<\/i> cells showed undetectable or decreased expression of the well\u2010known SASP factors: interleukin\u20106 (IL6), IL8, IL1\u03b1, growth\u2010related oncogene alpha (GRO\u03b1), SerpinB2, and intercellular adhesion molecule (ICAM\u20101). Apparently, due to the efficient DNA repair in <i><i>Spalax<\/i>,<\/i> senescent cells did not accumulate the DNA damage necessary for SASP activation. Conversely, <i>Spalax<\/i> can maintain DNA integrity during replicative or moderate genotoxic stress and limit pro\u2010inflammatory secretion. However, exposure to the conditioned medium of breast cancer cells MDA\u2010MB\u2010231 resulted in an increase in DNA damage, activation of the nuclear factor \u03baB (NF\u2010\u03baB) through nuclear translocation, and expression of inflammatory mediators in RS <i>Spalax<\/i> cells. Evaluation of SASP in aging <i>Spalax<\/i> brain and intestine confirmed downregulation of inflammatory\u2010related genes. These findings suggest a natural mechanism for alleviating the inflammatory response during cellular senescence and aging in <i><i>Spalax<\/i>,<\/i> which can prevent age\u2010related chronic inflammation supporting healthy aging and longevity.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The blind mole rat (Spalax) is a wild, long\u2010lived rodent that has evolved mechanisms to tolerate hypoxia and resist cancer. Previously, we demonstrated high DNA repair capacity and low DNA damage in Spalax fibroblasts following genotoxic stress compared with rats. Since the acquisition of senescence\u2010associated secretory phenotype (SASP) is a consequence of persistent DNA damage, [\u2026]<\/p>\n","protected":false},"author":511,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,269,47],"tags":[],"class_list":["post-97617","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-life-extension","category-neuroscience"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/97617","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=97617"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/97617\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=97617"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=97617"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=97617"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}