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Extended lifespan and long telomeres in rectal fibroblasts from late-onset ulcerative colitis patients

Lookup NU author(s): Dr Carmen Martin-Ruiz, Dr Joao Passos, Professor Thomas von Zglinicki

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Abstract

OBJECTIVES: Ulcerative colitis (UC) is characterized by damage to the intestinal epithelium and connective tissue. The causes of this damage could include changes in the ability of colonic fibroblasts to heal wounds and maintain epithelial cell proliferation. Telomeres shorten with each cell division and eventually signal senescence. The aim of this study is to investigate whether the impaired function of rectal fibroblasts in UC is due to accelerated telomere shortening, oxidative stress and premature senescence. METHODS: We isolated rectal fibroblasts from eight UC patients and nine non-colitis controls, and recorded their in-vitro lifespans. Telomere lengths and superoxide dismutase mRNA expression were also measured by real-time polymerase chain reaction and peroxide levels were measured by flow cytometry. RESULTS: The fibroblast lifespan decreased as patient age increased (R 2=0.68, P=0.003) in control patients, but this relationship was absent in UC fibroblasts. We identified a group of patients who were diagnosed later in life than a second group (59 versus 35 years, P=0.002). Fibroblasts from these late-onset UC patients underwent significantly more population doublings before senescence than age-matched controls (25 versus 15, P=0.02). Slower in-vitro telomere shortening rates (32 versus 344, P=0.006) and trends towards longer telomeres at explant were also observed in late-onset UC fibroblasts. Peroxide levels correlated positively with telomere shortening rate (r=0.581, P=0.078). CONCLUSIONS: Some UC-predisposed individuals may have more efficient antioxidant systems that protect the telomeres from oxidative damage. This may allow their rectal fibroblasts to live longer, function better and thus delay the onset of the disease until later life. © 2006 Lippincott Williams & Wilkins.


Publication metadata

Author(s): Getliffe KM, Martin Ruiz C, Passos JF, Von Zglinicki T, Nwokolo CU

Publication type: Article

Publication status: Published

Journal: European Journal of Gastroenterology and Hepatology

Year: 2006

Volume: 18

Issue: 2

Pages: 133-141

ISSN (print): 0954-691X

ISSN (electronic): 1473-5687

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1097/00042737-200602000-00005

DOI: 10.1097/00042737-200602000-00005

PubMed id: 16394794


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