Telomere length in cardiovascular disease and type 2 diabetes.
Doctoral thesis, UCL (University College London).
Telomere attrition during mitosis is thought to be a mechanism for cell senescence, which is induced when the mean length reduces below a critical value. Oxidative DNA damage has been suggested to cause greater telomere loss per cell division. Thus telomere length indicates the cells' replicative capacity and "biological age". Premature tissue ageing and senescence are major features of cardiovascular disease (CVD) and type 2 diabetes (T2D), and as such telomere length might play an important role in their pathogenesis. The aim of this thesis was to explore the association of telomere length with CVD and type 2 diabetes (T2D) as well as the CVD/T2D risk factors determining telomere length. The present study showed that telomere length is shorter in CVD and T2D patients compared to healthy subjects. As to what determines telomere length, I found that at least in the case of CVD, it can in part be partly attributed to inherited short telomeres, expressing the family history of the disease. At the same time, in diabetes patients I have observed that high oxidative stress, probably induced by the disease risk factors in the patients, is associated with greater telomere shortening. The later was consistent with the association found between variation in genes regulating reactive oxygen species levels, and shorter telomeres. I further examined the possible determinants of telomere shortening with in vitro experiments on ageing fibroblasts. In this case, the effect of glucose-induced oxidative stress and/or pro-inflammatory conditioning on telomere shortening was tested. The results showed that pro-inflammatory conditioning, partly by inducing an increased cell turnover, aggravates the shortening of telomeres in long-term culture. Telomere length may prove to be very useful in the management and possibly the prediction of CVD and diabetes, representing the contribution to their pathology of age, oxidative stress and chronic inflammation.
|Title:||Telomere length in cardiovascular disease and type 2 diabetes|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
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