Rise in insulin resistance is associated with escalated telomere attrition

Hypertension Research Center, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA.
Circulation (Impact Factor: 14.95). 06/2005; 111(17):2171-7. DOI: 10.1161/01.CIR.0000163550.70487.0B
Source: PubMed

ABSTRACT Insulin resistance predisposes to cardiovascular disease and shortens human lifespan. We therefore tested the hypothesis that a rise in insulin resistance in concert with gain in body mass is associated with accelerated white blood cell telomere attrition.
We measured white blood cell telomere dynamics and age-related changes in insulin resistance and body mass index in young adults of the Bogalusa Heart Study. Over 10.1 to 12.8 years, the relative changes in telomere length were correlated with the homeostasis model assessment of insulin resistance (r=-0.531, P<0.001) and changes in the body mass index (r=-0.423, P<0.001).
These findings provide the first tangible nexus of telomere biology with insulin resistance and adiposity in humans.

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    • "Telomere length is thought to influence the changes associated with aging, and the rate of telomere attrition has been associated with insulin resistance (Gardner et al., 2005). However, whether insulin resistance causes telomere shortening or longer telomeres have a role in maintaining insulin sensitivity is unclear (Gardner et al., 2005). "
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    ABSTRACT: Objective To assess the effect of parental age at childbirth on insulin sensitivity and other metabolic outcomes in overweight middle-aged males.Methods We studied 73 men aged 46.0±5.4 years, who were overweight (body mass index, BMI 25-30 kg/m2) but otherwise healthy. Insulin sensitivity was assessed by the Matsuda method from an oral glucose tolerance test. Other assessments included dual-energy X-ray absorptiometry-derived body composition, lipid profile, 24-hour ambulatory blood pressure, and carotid intima-media thickness. Maternal and paternal ages were highly correlated (r = 0.71; P < 0.0001), and the main parameter of interest in this study was the mean parental age at childbirth (MPAC), calculated as the average of maternal and paternal ages.ResultsIncreasing MPAC was associated with a continuous increase in insulin sensitivity (β = 0.193; P = 0.008), as well as reductions in insulin resistance (HOMA-IR; β = −0.064; P = 0.011), fasting insulin (β = −0.221; P = 0.018) and fasting glucose (β = −0.030; P = 0.033) concentrations. Increasing MPAC was also associated with reductions in night time systolic (β = −0.500; P = 0.020) and diastolic (β = −0.325; P = 0.047) blood pressure, as well as with improved (greater) nocturnal diastolic blood pressure dipping (β = 0.413; P = 0.046). Subgroup analyses on participants of European descent (n = 64) showed that increasing MPAC was associated with reduced carotid intima-media thickness (β = −0.008; P = 0.018) and lower low-density lipoprotein cholesterol concentrations (β = −0.042; P = 0.028).Conclusions Increasing parental age at childbirth was associated with a more favorable metabolic phenotype in overweight middle-aged males. However, it is unknown whether the effect was maternal, paternal, or both. Future studies on the effects of parental age at childbirth on the metabolism of males and females across the BMI range are required. Am. J. Hum. Biol. 27:380-386, 2015. © 2014 Wiley Periodicals, Inc.
    American Journal of Human Biology 11/2014; 27(3). DOI:10.1002/ajhb.22654 · 1.93 Impact Factor
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    • "Metabolic factors, including a greater body mass index (BMI), abdominal fat, and increased circulating glucose levels, have been related to shorter TL and lower telomerase activity (Epel et al., 2006; Valdes et al., 2005). Increases in body mass index, and in particular, insulin resistance, predict telomere shortening over a 10—13 year period (Gardner et al., 2005). Further, higher levels of nocturnal cortisol excretion, an indicator of chronic stress, are related to shorter TL (Epel et al., 2006). "
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    ABSTRACT: Psychological distress and metabolic dysregulation are associated with markers of accelerated cellular aging, including reduced telomerase activity and shortened telomere length. We examined whether participation in a mindfulness-based intervention, and, secondarily, improvements in psychological distress, eating behavior, and metabolic factors are associated with increases in telomerase activity in peripheral blood mononuclear cells (PBMCs). We enrolled 47 overweight/obese women in a randomized waitlist-controlled pilot trial (n=47) of a mindfulness-based intervention for stress eating and examined changes in telomerase activity from pre- to post-intervention. In secondary analyses, changes in telomerase activity across the sample were examined in relation to pre- to post-intervention changes in psychological distress, eating behavior, and metabolic factors (weight, serum cortisol, fasting glucose and insulin, and insulin resistance). Both groups increased in mean telomerase activity over 4 months in intent-to-treat and treatment efficacy analyses (p<0.001). Nonsignificant trends showed that greater attendance was associated with increases in telomerase, and telomerase increases were 18% higher among 'as treated' participants compared to controls. Across groups, changes in chronic stress, anxiety, dietary restraint, dietary fat intake, cortisol, and glucose were negatively correlated with changes in telomerase activity. In exploratory analyses, decreases in dietary fat intake partially mediated the association between dietary restraint and telomerase activity with marginal significance. While there was no clear effect of the intervention on telomerase activity, there was a striking pattern of correlations between improvements in psychological distress, eating behavior, and metabolic health and increases in telomerase activity. These findings suggest that telomerase activity may be in part regulated by levels of both psychological and metabolic stress.
    Psychoneuroendocrinology 12/2011; 37(7):917-28. DOI:10.1016/j.psyneuen.2011.10.008 · 5.59 Impact Factor
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    • "t al . 1999 ) . Telomere length , a tandem repeat of DNA sequence at the ends of eukaryotic chromosomes , has been shown to be a marker of oxidative stress ( Saretzki 2009 ) and has been inversely related to several chronic diseases , such as CAD ( Brouilette et al . 2008 ) , as well as obesity ( Nordfjall et al . 2008 ) , and insulin resistance ( Gardner et al . 2005 ) . Studies have shown that there is a rapid decrease in telomere length in the first four years of life ( Rufer et al . 1999 ) , a decline again in early adult life , and gradual progress with advancing age ( Frenck et al . 1998 ) . A significant association between obesity and telomere length has been observed in adults but not in chi"
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    ABSTRACT: The number of centenarians is growing worldwide. This specific cohort has aroused the attention of scientists worldwide and is considered one of the most valuable models to study the mechanisms involved in the aging process. In fact, they have reached the extreme limits of human life span and, most important of all, they show relatively good health being able to perform their routine daily life. Because they have escaped the common lethal diseases, the role of their genetic background has been brought into focus. In fact, sequence variations, in a variety of pro- or anti-inflammatory cytokine genes, have been found to influence successful ageing and longevity. The key role played by cytokines has been also confirmed in centenarians as we know that inflammation has been related to several pathological burdens (e.g., obesity, atherosclerosis, and diabetes). Successful ageing seems to be related to an optimal functioning of the immune system, pointing out that polymorphisms for the immune system genes, which are involved in the regulation of immune-inflammatory responses, may play a key role in the genetics of ageing. This review provides an update in the field of ageing related to inflammation and genetics.
    Human Biology 08/2011; 83(4):531-59. DOI:10.3378/027.083.0407 · 1.52 Impact Factor
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