title: Telomeres, NAFLD and Chronic Liver Disease.
abstract: Telomeres consist of repeat DNA sequences located at the terminal portion of chromosomes that shorten during mitosis, protecting the tips of chromosomes. During chronic degenerative conditions associated with high cell replication rate, progressive telomere attrition is accentuated, favoring senescence and genomic instability. Several lines of evidence suggest that this process is involved in liver disease progression: (a) telomere shortening and alterations in the expression of proteins protecting the telomere are associated with cirrhosis and hepatocellular carcinoma; (b) advanced liver damage is a feature of a spectrum of genetic diseases impairing telomere function, and inactivating germline mutations in the telomerase complex (including human Telomerase Reverse Transcriptase (hTERT) and human Telomerase RNA Component (hTERC)) are enriched in cirrhotic patients independently of the etiology; and (c) experimental models suggest that telomerase protects from liver fibrosis progression. Conversely, reactivation of telomerase occurs during hepatocarcinogenesis, allowing the immortalization of the neoplastic clone. The role of telomere attrition may be particularly relevant in the progression of nonalcoholic fatty liver, an emerging cause of advanced liver disease. Modulation of telomerase or shelterins may be exploited to prevent liver disease progression, and to define specific treatments for different stages of liver disease.
authors.affiliation: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano, 20122 Milano, Italy. benedetta.donati@unimi.it.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Donati
authors.affiliation: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano, 20122 Milano, Italy. luca.valenti@unimi.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Valenti
mesh_terms: D018450:Disease Progression; D006801:Humans; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012313:RNA / Q000378:metabolism; D000089804:Shelterin Complex; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics* / Q000378:metabolism; D059506:Telomere Shortening; D034501:Telomere-Binding Proteins / Q000378:metabolism
chemical_list: D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase
keywords: cirrhosis; hepatocellular carcinoma; liver disease progression; nonalcoholic fatty liver disease; telomerase; telomere