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      Telomere Length Attrition, a Marker of Biological Senescence, Is Inversely Correlated with Triglycerides and Cholesterol in South Asian Males with Type 2 Diabetes Mellitus

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          Abstract

          South Asians have a higher risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) than white Caucasians, for a given BMI. Premature biological ageing, assessed by reduction in telomere length (TL), may be mediated by factors resulting from altered metabolic profiles associated with obesity. We hypothesise that ethnicity and metabolic status represent detrimental factors contributing to premature biological ageing. Therefore we assessed TL in two South Asian, age and BMI-matched cohorts [T2DM ( n = 142) versus non-T2DM ( n = 76)] to determine the effects of BMI, gender, lipid and CVD profile on biological ageing. Genomic DNA was obtained from the UKADS cohort; biochemical and anthropometric data was collected and TL was measured by quantitative real-time PCR. Our findings indicated a gender-specific effect with reduced TL in T2DM men compared with non-T2DM men ( P = 0.006). Additionally, in T2DM men, TL was inversely correlated with triglycerides and total cholesterol ( r = −0.419, P < 0.01; r = −0.443, P < 0.01). In summary, TL was reduced amongst South Asian T2DM men and correlated with triglycerides and total cholesterol. This study highlights enhanced biological ageing among South Asian, T2DM men, which appears to be tracked by changes in lipids and BMI, suggesting that raised lipids and BMI may directly contribute to premature ageing.

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          Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins.

          Paula Martinez, Maria Blasco (2011)
          Mammalian telomeres are formed by tandem repeats of the TTAGGG sequence, which are progressively lost with each round of cell division. Telomere protection requires a minimal length of TTAGGG repeats to allow the binding of shelterin, which prevents the activation of a DNA damage response (DDR) at chromosome ends. Telomere elongation is carried out by telomerase. Telomerase can also act as a transcriptional modulator of the Wnt-β-catenin signalling pathway and has RNA-dependent RNA polymerase activity. Dysfunctional telomeres can lead to either cancer or ageing pathologies depending on the integrity of the DDR. This Review discusses the role of telomeric proteins in cancer and ageing through modulating telomere length and protection, as well as regulating gene expression by binding to non-telomeric sites.
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            Obesity-related non-communicable diseases: South Asians vs White Caucasians.

            A. K. Misra, Madan L. Khurana (2011)
            South Asians are at higher risk than White Caucasians for the development of obesity and obesity-related non-communicable diseases (OR-NCDs), including insulin resistance, the metabolic syndrome, type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). Rapid nutrition and lifestyle transitions have contributed to acceleration of OR-NCDs in South Asians. Differences in determinants and associated factors for OR-NCDs between South Asians and White Caucasians include body phenotype (high body fat, high truncal, subcutaneous and intra-abdominal fat, and low muscle mass), biochemical parameters (hyperinsulinemia, hyperglycemia, dyslipidemia, hyperleptinemia, low levels of adiponectin and high levels of C-reactive protein), procoagulant state and endothelial dysfunction. Higher prevalence, earlier onset and increased complications of T2DM and CHD are often seen at lower levels of body mass index (BMI) and waist circumference (WC) in South Asians than White Caucasians. In view of these data, lower cut-offs for obesity and abdominal obesity have been advocated for Asian Indians (BMI; overweight >23 to 24.9 kg m(-2) and obesity ≥ 25 kg m(-2); and WC; men ≥ 90 cm and women ≥ 80 cm, respectively). Imbalanced nutrition, physical inactivity, perinatal adverse events and genetic differences are also important contributory factors. Other differences between South Asians and White Caucasians include lower disease awareness and health-seeking behavior, delayed diagnosis due to atypical presentation and language barriers, and religious and sociocultural factors. All these factors result in poorer prevention, less aggressive therapy, poorer response to medical and surgical interventions, and higher morbidity and mortality in the former. Finally, differences in response to pharmacological agents may exist between South Asians and White Caucasians, although these have been inadequately studied. In view of these data, prevention and management strategies should be more aggressive for South Asians for more positive health outcomes. Finally, lower cut-offs of obesity and abdominal obesity for South Asians are expected to help physicians in better and more effective prevention of OR-NCDs.
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              Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity.

              Athanase Benetos, Koji Okuda, Malika Lajémi … (2001)
              Chronological age is the primary determinant of stiffness of central arteries. Increased stiffness is an independent indicator of cardiovascular risk. The aim of this study was to determine whether telomere length, a possible index of biological aging, provides a better account than chronological age for variation in arterial stiffness, evaluated by measuring pulse pressure and aortic pulse wave velocity. The study population included 193 French subjects (120 men, 73 women), with a mean age of 56+/-11 years, who were not on any antihypertensive medications. Telomere length was evaluated in white blood cells by measuring the mean length of the terminal restriction fragments. Age-adjusted telomere length was longer in women than in men (8.67+/-0.09 versus 8.37+/-0.07 kb; P=0.016). In both genders, telomere length was inversely correlated with age (P<0.01). Multivariate analysis showed that in men, but not in women, telomere length significantly contributed to pulse pressure and pulse wave velocity variations. In conclusion, telomere length provides an additional account to chronological age of variations in both pulse pressure and pulse wave velocity among men, such that men with shorter telomere length are more likely to exhibit high pulse pressure and pulse wave velocity, which are indices of large artery stiffness. The longer telomere length in women suggests that for a given chronological age, biological aging of men is more advanced than that of women.
              Article 0 comments Cited 110 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Exp Diabetes Res
                Journal ID (iso-abbrev): Exp Diabetes Res
                Journal ID (publisher-id): EDR
                Title: Experimental Diabetes Research
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 1687-5214
                ISSN (Electronic): 1687-5303
                Publication date (Print): 2012
                Publication date (Electronic): 1 March 2012
                Volume: 2012
                Electronic Location Identifier: 895185
                Affiliations
                1Clinical Sciences Research Laboratories, Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, University Hospital Coventry and Warwickshire, Coventry CV2 2DX, UK
                2AstraZeneca R&D, CVGI Bioscience, Mereside, Alderley Park, Macclesfield, Chesire SK1 04TG, UK
                3University of Birmingham and Biomedical Research Centre, Heart of England NHS Foundation Trust, Birmingham B4 7ET, UK
                4Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
                5Center of Excellence in Biotechnology, King Saud University, Riyadh 11451, Saudi Arabia
                6Aston University, Birmingham B4 7ET, UK
                Author notes

                Academic Editor: Toshiyasu Sasaoka

                Article
                DOI: 10.1155/2012/895185
                PMC ID: 3303685
                PubMed ID: 22474429
                SO-VID: 10de16fb-4058-4c2e-88d1-e372299f758f
                Copyright © Copyright © 2012 Alison L. Harte et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 17 September 2011
                Date revision received : 14 November 2011
                Date accepted : 21 November 2011
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Endocrinology & Diabetes
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes

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