The role of cellular senescence in the gastrointestinal mucosa

• Published in: Gut and liver Vol. 7; no. 3; pp. 270 - 277
• Main Authors: Penfield, Joshua D, Anderson, Marlys, Lutzke, Lori, Wang, Kenneth K
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society of Gastroenterology; the Korean Society of Gastrointestinal Endoscopy; the Korean Association for the Study of the Liver; the Korean Society of Neurogastroenterology and Motility; Korean Association for the Study of Intestinal Diseases; Korean College of Helicobacter and Upper Gastrointestinal Research; Korean Pancreatobiliary Association; Korean Society of Gastrointestinal Cancer 01-05-2013; Gastroenterology Council for Gut and Liver; 거트앤리버 소화기연관학회협의회
• Subjects: aging; cell aging; gastrointestinal mucosa; gastrointestinal neoplasms; Review; 내과학; Aging; Gastrointestinal mucosa; Cell aging; Gastrointestinal neoplasms
• ISSN: 1976-2283; 2005-1212
• DOI: 10.5009/gnl.2013.7.3.270

Cellular senescence is a biologically irreversible state of cell-growth arrest that occurs following either a replicative or an oncogenic stimulus. This phenomenon occurs as a response to the presence of premalignant cells and appears to be an important anticancer mechanism that keeps these transformed cells at bay. Many exogenous and endogenous triggers for senescence have been recognized to act via genomic or epigenomic pathways. The most common stimulus for senescence is progressive loss of telomeric DNA, which results in the loss of chromosomal stability and eventual unregulated growth and malignancy. Senescence is activated through an interaction between the p16 and p53 tumor-suppressor genes. Senescent cells can be identified in vitro because they express senescence-associated β-galactosidase, a marker of increased lysosomal activity. Cellular senescence plays an integral role in the prevention and development of both benign and malignant gastrointestinal diseases. The senescence cascade and the cell-cycle checkpoints that dictate the progression and maintenance of senescence are important in all types of gastrointestinal cancers, including pancreatic, liver, gastric, colon, and esophageal cancers. Understanding the pathogenic mechanisms involved in cellular senescence is important for the development of agents targeted toward the treatment of gastrointestinal tumors.