Biomarkers of oxidative stress: methods and measures of oxidative DNA damage (COMET assay) and telomere shortening

Oxidative stress is fast becoming the nutritional and medical buzzword for the twenty-first century. The theoretical importance of oxidative stress in diabetes is highlighted by its potential double impact on metabolic dysfunction on one hand and the vascular system on the other hand. The new concept of oxidative stress, being an important trigger in the onset and progression of diabetes and its complications, emphasizes the need for measurement of markers of oxidation to assess the degree of oxidative stress. While we have been routinely measuring biomarkers in our molecular epidemiology projects, here we discuss the utility of two assays, (a) DNA damage assessment by COMET measurement and (b) telomere length measurement. As DNA damage is efficiently repaired by cellular enzymes, its measurement gives a snapshot view of the level of oxidative stress. The protocol allows for measurement of oxidative DNA damage (FPG-sensitive DNA strand breaks). Telomere length measured by Southern blotting technique allows one to estimate the chronic burden of oxidative stress at the molecular level and is now considered as biomarker of biological aging

Socioeconomic status and telomere length: the West of Scotland Coronary Prevention Study

<b>Background</b>: It has been hypothesised that socioeconomically deprived people age more rapidly than their more advantaged counterparts and this is biologically manifest in shorter telomeres. However, in the very few studies conducted, substantial uncertainty exists regarding this relationship. <b>Methods</b>: In the present investigation, 1542 men in the West of Scotland Coronary Prevention Study responded to a series of enquiries about their socioeconomic position (educational attainment, employment status, area-based deprivation), had their physical stature measured (a proxy for early life social circumstances) and provided a blood specimen from which leucocyte DNA was extracted and telomere length derived. <b>Results</b>: There was no strong evidence that any of these four indices of socioeconomic position was robustly related to telomere length. The only exception was employment status: men who reported being out of work had significantly shorter telomeres than those who were employed (p = 0.007). <b>Conclusion</b>: In this cross-sectional study—the largest to date to examine the relationship—we found little evidence of an association between socioeconomic status and telomere length

Association of increased telomere lengths in limited scleroderma, with a lack of age-related telomere erosion

<p><b>Objectives</b>: Telomere erosion, a feature of biological ageing, is implicated in a wide range of diseases. Its impact on autoimmune diseases remains unclear although autoantibodies against many telomere nucleoprotein components are prevalent in these diseases. We aimed to assess if telomere biology was abnormal in a cohort of patients with limited cutaneous systemic sclerosis (lcSSc).</p> <p><b>Methods</b>: Telomere lengths in peripheral blood leucocytes (PBL) were determined using Southern blotting methods in a cohort of lcSSc subjects (n = 43; age range 37–80 years) and a control population (n = 107; age range 21–65 years).</p> <p><b>Results</b>: Telomere lengths in lcSSc subjects were longer than controls (p<0.001), did not show age-related telomere erosion and differed significantly from age-matched controls only after 50 years of age (p<0.001).</p> <p><b>Conclusions</b>: This is the first report of maintenance of telomere lengths in an autoimmune disease state. These data indicate aberrant telomere biology and irregular biological ageing from the fifth decade of life. These findings provide insight into compromised DNA damage repair in lcSSc. Whether these observations indicate a causal or consequential relationship requires further investigation. This in turn, may provide potential novel targets for therapeutic intervention.</p&gt