Getliffe, K.M.; Aldulaimi, D.M.; Nwokolo, C.U.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA61
Academic Journal
Introduction: Human somatic cells have a finite lifespan and cease to divide after a certain number of cell divisions, a phenomenon known as replicative senescence. One mechanism believed to trigger this process is continuous shortening of chromosomal ends (telomeres), with each cell division until a critical length is reached at which cell replication ceases. In cancerous and normal proliferating cells (including the epithelial cells of the bowel) this mechanism can be bypassed by telomerase, which adds telomeric repeats to the ends of chromosomes to maintain their length and thereby prevent senescence. A telomerase knockout mouse suffers ulceration and atrophy of the bowel. In ulcerative colitis (UC), the colonic mucosa is deficient in telomerase and epithelial cells in inflamed areas have short telomeres. Furthermore, in UC patients we have observed a decrease in lymphocyte telomerase activity and others have found lymphocyte chromosomal abnormalities. Aim: To determine whether these observations are caused simply by the increased cell turnover inherent in the inflammatory process or whether UC patients have a global telomere maintenance defect which contributes to the disease. Methods: Rectal fibroblast cultures were generated from 9 UC patients and 9 age-matched non-UC controls; their rates of senescence and telomere lengths were assessed throughout their life span in culture. Senescence rates were measured by counting the percentage of cells staining for the proliferation marker Ki67 at each passage and telomere lengths were measured using a standard TRF measurement southern blotting assay. Results: Preliminary results have identified little difference between the rates of senescence in UC and non-UC fibroblasts, suggesting that telomere/telomerase dysfunction is not global but may be a downstream effect of inflammation in this disease. However, this study is ongoing and further cultures are in the process of being analysed.


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