[Telomere biology and metabolic disorders: the role of insulin resistance and type 2 diabetes].

BACKGROUND: Insulin resistance accelerates the aging process, but its speed depends on the individual characteristics of the metabolism. One of the reasons for the different aging rates in individuals with insulin resistance is the initially different "genetic protection" of cells, which many scientists associate with replicative cellular aging. AIMS: to study the relationship between the state of carbohydrate metabolism and markers of replicative cell aging in individuals with different sensitivity to insulin. MATERIALS AND METHODS: The observation study included 305 patients. The parameters of glucose metabolism and telomere biology were studied. RESULTS: The mean age of the patients was 51.5±13.3 years. Patients were divided into three groups depending on presence of insulin resistance: healthy, with insulin resistance and with type 2 diabetes. The mean age of healthy patients was 48.82±13.87 years, in insulin resistance group - 53.04±12.8, in 2 diabetes mellitus - 58.4±7.90. The median telomere length was 9.76. The median telomerase activity was 0.48. Both telomere length and telomerase activity progressively decrease as insulin resistance increases. In patients with diabetes, short telomere lengths and low telomerase activity predominated. The insulin resistance index has the greatest impact on the risk of detecting "short" telomeres. In patients with insulin resistance, an increase in glycated hemoglobin increases the likelihood of detecting short telomeres by 2.4 times, and in diabetes mellitus by 4.26 times, an increase in fasting plasma glucose by 90%, and an increase in HOMA-IR by 35%. An increase in insulin resistance increases the risk of detecting «low¼ telomerase activity by 53% and the risk of detecting «very low¼ telomerase activity by 92%. A decrease in synsulin resistance increases the chance of increasing telomerase activity to «very high¼ by 51%. CONCLUSION: Shorter telomeres are associated with more pronounced disorders of carbohydrate metabolism and a higher degree of insulin resistance. Further studies of metabolic status are necessary to personalize their lifestyle and treatment goals.

Growth Hormone, Insulin-Like Growth Factor-1, Insulin Resistance, and Leukocyte Telomere Length as Determinants of Arterial Aging in Subjects Free of Cardiovascular Diseases.

Background: Increased arterial stiffness (AS), intima-media thickness (IMT), and the presence of atherosclerotic plaques (PP) have been considered as important aspects of vascular aging. It is well documented that the cardiovascular system is an important target organ for growth hormone (GH) and insulin-like growth factor (IGF)-1 in humans, and GH /IGF-1 deficiency significantly increases the risk for cardiovascular diseases (CVD). The telomere length of peripheral blood leukocytes (LTL) is a biomarker of cellular senescence and that has been proposed as an independent predictor of (CVD). The aim of this study is to determine the role of GH/IGF-1, LTL and their interaction cardiovascular risk factors (CVRF) in the vascular aging. Methods: The study group included 303 ambulatory participants free of known CVD (104 males and 199 females) with a mean age of 51.8 ± 13.3 years. All subjects had one or more CVRF [age, smoking, arterial hypertension, obesity, dyslipidemia, fasting hyperglycemia, insulin resistance-HOMA (homeostatic model assessment) >2.5, or high glycated hemoglobin]. The study sample was divided into the two groups according to age as "younger" (m ≤ 45 years, f ≤ 55 years) and "older" (m > 45 years, f > 55 years). IMT and PP were determined by ultrasonography, AS was determined by measuring the carotid-femoral pulse wave velocity (c-f PWV) using the SphygmoCor system (AtCor Medical). LTL was determined by PCR. Serum IGF-1 and GH concentrations we measured by immunochemiluminescence analysis. Results: Multiple linear regression analysis with adjustment for CVRF indicated that HOMA, GH, IGF-1, and LTL had an independent relationship with all the arterial wall parameters investigated in the younger group. In the model with c-f PWV as a dependent variable, p < 0.001 for HOMA, p = 0.03 for GH, and p = 0.004 for LTL. In the model with IMT as a dependent variable, p = 0.0001 for HOMA, p = 0.044 for GH, and p = 0.004 for IGF-1. In the model with the number of plaques as a dependent variable, p = 0.0001 for HOMA, and p = 0.045 for IGF-1. In the older group, there were no independent significant associations between GH/IGF-1, LTL, HOMA, and arterial wall characteristics. Conclusions: GH/IGF-1, IR, HOMA, and LTL were the important parameters of arterial aging in younger healthy participants.

Age-Related Left Ventricular Changes and Their Association with Leukocyte Telomere Length in Healthy People.

INTRODUCTION: With advancing age the left ventricle (LV) undergoes structural and functional changes, thereby creating the substrate for the development of diseases. One possible mechanism of the ageing heart is a cellular senescence. Leukocyte telomere length (LTL) is a marker of replicative ageing. The purpose of this study was to evaluate the structure and function of the LV in people of different ages free of cardiovascular diseases (CVD) and regular drug medication and to assess their relationship with LTL. We hypothesized that age-related changes in LV myocardium are associated with telomere length. METHODS: The study population consisted of 150 healthy, non-obese volunteers aged 28 to 78 years without history of CVD, significant deviations by 12-lead electrocardiogram and negative exercise test (treadmill stress test). All the participants underwent standardized transthoracic echocardiography using an available system (iE33; Philips). The LTL was measured by real-time quantitative polymerase chain reaction. We determined the relative ratio of telomere repeat copy number (T) to single-copy gene copy number (S). RESULTS: In the older people there was a higher wall thickness than in the younger (1.03 ± 0.09 vs. 0.88 ± 0.10, p<0.01), whereas LV mass index was comparable between them (85.8 ± 15.40 vs. 83.1 ± 11.8, p = 0.20). There was a decrease in LV dimensions with advancing age (p<0.001). Older subjects had impairment in LV relaxation. LTL was associated with decreased E/A, Em/Am ratio (ß = -0.323, p = 0.0001) after adjusting for age, sex and risk factors. There is no relation between the LTL and the structure of LV. CONCLUSIONS: Our data suggest that the ageing process leads to changes in LV structure and diastolic function and is linked with a phenotype of concentric LV remodeling. Telomere attrition is associated with age-related LV diastolic dysfunction. Telomere length appears to be a biomarker of myocardial ageing.