Masi, S; (2014) Leukocyte telomere length, inflammation and age-related diseases. Doctoral thesis , UCL (University College London).

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Abstract

Background: Aging is a physiological process characterised by a progressive dysfunction in metabolism and impaired tissue repair capacity, eventually leading to organs’ and tissue degeneration. Low-grade inflammation is currently considered the main driver of aging. The measure of telomeres length in peripheral leukocytes (LTL) has been suggested as novel and reliable marker of aging. The aim of this PhD was to investigate the association between (LTL), chronic inflammation and common cardio-metabolic risk factors. Methods: Four studies were conducted: 1) a case-control analysis of 356 cases with periodontitis (PD) and 206 controls to assess the differences in LTL between cases and controls, 2) a cross sectional analysis of 630 individuals with diabetes mellitus investigating the association between PD, LTL and gluco-metabolic factors, 3) a cross-sectional analysis of 1080 adolescents (13–16 years old) to investigate the association between LTL, inflammation and cardiovascular (CV) disease risk factors and 4) a 10 years longitudinal analysis in 2547 women and 2815 men to assess whether LTL predicted cardiac and vascular phenotypes. LTL were measured using a Real Time Polymerase Chain Reaction method in all studies. Results: Study I demonstrated that increased systemic inflammation and oxidative stress were associated with shorter LTL in cases with PD versus controls (P<0.05). Results from Study II confirmed that shorter LTL was associated with severe periodontal inflammation (p=0.04), increased endotoxemia and insulin resistance. In Study III LTL was inversely associated with C-reactive protein (P<0.001) and fibrinogen (P=0.001) in adolescents. Lastly in Study IV a faster rate of telomere shortening between 53 to 60-64 years was associated with subclinical atherosclerosis at 60-64 years (p=0.006). All results were independent of traditional CV risk factors. Conclusions: This PhD programme provides evidence in support of the use of LTL as novel marker of aging and predictor of age-related diseases.

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