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: 14.43). 06/2005; 111(17):2171-7. DOI: 10.1161/01.CIR.0000163550.70487.0B
Source: PubMed


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.

11 Reads
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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 · 1.70 Impact Factor
  • Source
    • "Although telomere length may predict clinical outcomes and mortality among humans, cells with shortened telomeres remain genetically stable if the telomere maintenance system, which includes mainly telomerase, is fully functioning [5]. Metabolic factors, such as abdominal fat and increased circulating glucose levels are related to shorter telomeres and lower telomerase activity [6]–[8], supporting the role of lifestyle and environmental factors on telomeres maintenance. The effect of diets on human health has already been evaluated in many studies while limited are evidences on the relative importance of dietary intake on telomeres maintenance and stability. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Leukocyte telomere length (LTL) and rate of telomere shortening are known biomarkers of aging while, numerous studies showed that Mediterranean diet (MD) may boost longevity. We studied association between telomere length, telomerase activity and different adherence to MD and its effects on healthy status. The study was conducted in 217 elderly subjects stratified according Mediterranean diet score (MDS) in low adherence (MDS≤3), medium adherence (MDS 4-5) and high adherence (MDS≥6) groups. LTL was measured by quantitative polymerase chain reaction and telomerase activity by a PCR-ELISA protocol. High adherence group showed longer LTL (p = 0.003) and higher telomerase activity (p = 0.013) compared to others. Linear regression analysis including age, gender, smoking habit and MDS showed that MDS was independently associated with LTL (p = 0.024) and telomerase activity levels (p = 0.006). Telomerase activity was independently associated with LTL (p = 0.007) and negatively modulated by inflammation and oxidative stress. Indeed, telomerase levels were associated with healthy status independently of multiple covariates (p = 0.048). These results support a novel role of MD in promoting health-span suggesting that telomere maintenance, rather than LTL variability is the major determinant of healthy status among elderly.
    PLoS ONE 04/2013; 8(4):e62781. DOI:10.1371/journal.pone.0062781 · 3.23 Impact Factor
  • Source
    • "In addition, a number of lifestyle factors, such as smoking, sleep duration, body mass index (BMI) and physical activity can alter telomere length [16,17]. Shorter TL has been associated with an overall detrimental effect on cardiovascular health [16,18-20] cancer and a spectrum of age-related disorders [21]. In addition, self-perceived psychological stress, as well as the chronicity of stress has been linked to shorter TL in humans [4,6]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Exposure to early adverse events can result in the development of later psychopathology, and is often associated with cognitive impairment. This may be due to accelerated cell aging, which can be catalogued by attritioned telomeres. Exercise enhances neurogenesis and has been proposed to buffer the effect of psychological stress on telomere length. This study aimed to investigate the impact of early developmental stress and voluntary exercise on telomere length in the ventral hippocampus (VH) and prefrontal cortex (PFC) of the rat. Forty-five male Sprague–Dawley rats were categorised into four groups: maternally separated runners (MSR), maternally separated non-runners (MSnR), non-maternally separated runners (nMSR) and non-maternally separated non-runners (nMSnR). Behavioural analyses were conducted to assess anxiety-like behaviour and memory performance in the rats, after which relative telomere length was measured using qPCR. Results Maternally separated (MS) rats exhibited no significant differences in either anxiety levels or memory performance on the elevated-plus maze and the open field compared to non-maternally separated rats at 49 days of age. Exercised rats displayed increased levels of anxiety on the day that they were removed from the cages with attached running wheels, as well as improved spatial learning and temporal recognition memory compared to non-exercised rats. Exploratory post-hoc analyses revealed that maternally separated non-exercised rats exhibited significantly longer telomere length in the VH compared to those who were not maternally separated; however, exercise appeared to cancel this effect since there was no difference in VH telomere length between maternally separated and non-maternally separated runners. Conclusions The increased telomere length in the VH of maternally separated non-exercised rats may be indicative of reduced cellular proliferation, which could, in turn, indicate hippocampal dysfunction. This effect on telomere length was not observed in exercised rats, indicating that voluntary exercise may buffer against the progressive changes in telomere length caused by alterations in maternal care early in life. In future, larger sample sizes will be needed to validate results obtained in the present study and obtain a more accurate representation of the effect that psychological stress and voluntary exercise have on telomere length.
    BMC Research Notes 12/2012; 5(1):697. DOI:10.1186/1756-0500-5-697
Show more

Similar Publications