Shortened leukocyte telomere length in type 2 diabetes mellitus: genetic polymorphisms in mitochondrial uncoupling proteins and telomeric pathways.
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ABSTRACT:
SUBMITTER: Zhou Y
PROVIDER: S-EPMC4781821 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
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Project description:Previous Studies have mapped putative loci that may probably regulate leukocyte telomere length (LTL). The strongest associations with LTL were reported for SNP rs12696304 and rs16847897 near the non-coding Ribose Nucleic Acid (RNA) molecule component (TERC) of telomerase enzyme on 3q26. It is unclear whether these identified loci coding functional components of telomerase, exert a similar effect on LTL in other populations or influence risk factors of Type 2 Diabetes Mellitus (T2DM). The present study was performed to: study the influence of TERC polymorphisms on LTL, human telomerase reverse transcriptase (hTERT), indices of obesity and explore the potential associations with T2DM. 225 T2DM patients and 245 age and sex matched controls were studied. Allelic Discrimination (AD) genotyping was utilized to determine TERC SNPs [rs12696304 and rs16847897]. hTERT, adiponectin, Insulin, Homeostasis Model Assessment (HOMA-IR), and LTL were measured. Body Mass Index (BMI) and waist circumference (WC) were recorded. [CC] genotype of rs16847897 was significantly associated with shorter LTL [OR = 1.6, p = 0.004], lower hTERT levels [OR = 0.4, p = 0.006], higher BMI [OR = 2.2, p = 0.006], larger WC [OR = 23.4, p = 0.007] and hypo-adiponectemia [OR = 0.6, p = 0.006]. [GG] genotype of rs12696304 was also significantly associated with shorter LTL [OR = 1.5, p = 0.004], lower hTERT [OR = 0.7, p = 0.006] but with larger WC[OR = 5.3, p = 0.004]. [CC] genotype of rs16847897 and [GG] genotype of rs12696304 together increased the risk of T2DM significantly [OR = 1.7, p = 0.004]. We provide insights connecting a structure that is critically involved in maintaining genomic stability with obesity and T2DM. Given the central role of telomere length in determining telomere function our findings may expand our understanding of the pathological mechanisms underlying age associated conditions such as T2DM.
| S-EPMC4705103 | biostudies-literature
Project description:The relationship between alcohol consumption and mortality generally exhibits a U-shaped curve. The longevity observed with moderate alcohol consumption may be explained by other confounding factors, and, if such a relationship is present, the mechanism is not well understood. Indeed, the optimal amount of alcohol consumption for health has yet to be determined. Leukocyte telomere length is an emerging quantifiable marker of biological age and health, and a shorter telomere length is a predictor of increased mortality. Because leukocyte telomere length is a quantifiable and objectively measurable biomarker of aging, we sought to identify the amount of alcohol consumption associated with the longest telomere length and least telomere length attrition. Among over 2,000 participants from two distinct cohort studies, we found no pattern of alcohol consumption that was associated with longer telomere length or less telomere length attrition over time. Binge drinking may reduce telomere length. Using telomere length as a marker of age and health, these data fail to demonstrate any benefits of alcohol consumption, even when consumed in moderation.
| S-EPMC6363724 | biostudies-literature
Project description:BACKGROUND:Telomere length is a marker of cellular aging that varies with the individual, is inherited, and is highly correlated across somatic cell types within persons. Interindividual variability of telomere length may partly explain differences in reproductive aging rates. We examined whether leukocyte telomere length was associated with menopausal age. METHODS:We evaluated the relationship between leukocyte telomere length and age at natural menopause in 486 white women ?65 years of age. We fit linear regression models adjusted for age, income, education, body mass index, physical activity, smoking, and alcohol intake. We repeated the analysis in women with surgical menopause. We also performed sensitivity analyses excluding women (1) with unilateral oophorectomy, (2) who were nulliparous, or (3) reporting menopausal age <40 years, among other exclusions. RESULTS:For every 1-kb increase in leukocyte telomere length, average age at natural menopause increased by 10.2 months (95% confidence interval = 1.3 to 19.0). There was no association among 179 women reporting surgical menopause. In all but one sensitivity analysis, the association between leukocyte telomere length and age at menopause became stronger. However, when excluding women with menopausal age <40 years, the association decreased to 7.5 months (-0.4 to 15.5). CONCLUSIONS:Women with the longest leukocyte telomere length underwent menopause 3 years later than those with the shortest leukocyte telomere length. If an artifact, an association would likely also have been observed in women with surgical menopause. If these results are replicated, leukocyte telomere length may prove to be a useful predictor of age at menopause.
| S-EPMC3926311 | biostudies-literature
Project description:PurposeBirdshot Uveitis (BU) is an archetypical chronic inflammatory eye disease, with poor visual prognosis, that provides an excellent model for studying chronic inflammation. BU typically affects patients in the fifth decade of life. This suggests that it may represent an age-related chronic inflammatory disease, which has been linked to increased erosion of telomere length of leukocytes.MethodsTo study this in detail, we exploited a sensitive standardized quantitative real-time polymerase chain reaction to determine the peripheral blood leukocyte telomere length (LTL) in 91 genotyped Dutch BU patients and 150 unaffected Dutch controls.ResultsAlthough LTL erosion rates were very similar between BU patients and healthy controls, we observed that BU patients displayed longer LTL, with a median of log (LTL) = 4.87 (= 74131 base pair) compared to 4.31 (= 20417 base pair) in unaffected controls (P<0.0001). The cause underpinning the difference in LTL could not be explained by clinical parameters, immune cell-subtype distribution, nor genetic predisposition based upon the computed weighted genetic risk score of genotyped validated variants in TERC, TERT, NAF1, OBFC1 and RTEL1.ConclusionsThese findings suggest that BU is accompanied by significantly longer LTL.
| S-EPMC5411068 | biostudies-literature
Project description:Adiposity may cause adverse health outcomes by increasing oxidative stress and systemic inflammation, which can be reflected by altered telomere length (TL) and mitochondrial DNA copy number (mtCN) in peripheral blood leukocytes. However, little is known about the influence of lifetime adiposity on TL and mtCN in later life. This study was performed to investigate the associations of lifetime adiposity with leukocyte TL and mtCN in 9613 participants from the Nurses' Health Study. A group-based trajectory modelling approach was used to create trajectories of body shape from age 5 through 60 years, and a genetic risk score (GRS) was created based on 97 known adiposity susceptibility variants. Associations of body shape trajectories and GRS with dichotomized TL and mtCN were assessed by logistic regression models. After adjustment for lifestyle and dietary factors, compared with the lean-stable group, the lean-marked increase group had higher odds of having below-median TL (OR = 1.18, 95% CI 1.04, 1.35; P = 0.01), and the medium-marked increase group had higher odds of having below-median mtCN (OR = 1.28, 95% CI 1.00, 1.64; P = 0.047). There was a suggestive trend toward lower mtCN across the GRS quartiles (P for trend = 0.07). In conclusion, telomere attrition may be accelerated by marked weight gain in middle life, whereas mtCN is likely to be reduced persistently by adiposity over the life course. The findings indicate the importance of lifetime weight management to preserve functional telomeres and mitochondria.
| S-EPMC8063494 | biostudies-literature
Project description:The nematode Caenorhabditis elegans, after completing its developmental stages and a brief reproductive period, spends the remainder of its adult life as an organism consisting exclusively of post-mitotic cells. Here we show that telomere length varies considerably in clonal populations of wild-type worms, and that these length differences are conserved over at least ten generations, suggesting a length regulation mechanism in cis. This observation is strengthened by the finding that the bulk telomere length in different worm strains varies considerably. Despite the close correlation of telomere length and clonal cellular senescence in mammalian cells, nematodes with long telomeres were neither long lived, nor did worm populations with comparably short telomeres exhibit a shorter life span. Conversely, long-lived daf-2 and short-lived daf-16 mutant animals can have either long or short telomeres. Telomere length of post-mitotic cells did not change during the aging process, and the response of animals to stress was found independent of telomere length. Collectively, our data indicate that telomere length and life span can be uncoupled in a post-mitotic setting, suggesting separate pathways for replication-dependent and -independent aging.
| S-EPMC1200426 | biostudies-literature
Project description:Leukocyte telomere length (LTL) is a complex genetic trait. It shortens with age and is associated with a host of aging-related disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n=3365), aged 18-94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring), the NHLBI Family Heart Study (NHLBI-Heart), the Longitudinal Study of Aging Danish Twins (Danish Twins), and the UK Adult Twin Registry (UK Twins). Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (<30 years) and older (>50 years) donors. Paternal age had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice of the annual attrition in LTL with age. Moreover, sperm telomere length analyses were compatible with the emergence in older men of a subset of sperm with elongated telomeres. Paternal age exerts a considerable effect on the offspring's LTL, a phenomenon which might relate to telomere elongation in sperm from older men. The implications of this effect deserve detailed study.
| S-EPMC2242810 | biostudies-literature
Project description:Leukocyte telomere length (LTL) and whole blood mitochondrial DNA (WB mtDNA) content are aging markers impacted by chronic diseases such as human immunodeficiency virus (HIV) infection. We characterized the relationship between these two markers in 312 women ≥12 years of age living with HIV and 300 HIV-negative controls. We found no relationship between the two markers cross-sectionally. In multivariable models, age, ethnicity, HIV, and tobacco smoking were independently associated with shorter LTL, and the former three with lower WB mtDNA. Longitudinally, among a subgroup of 228 HIV participants and 68 HIV-negative controls with ≥2 biospecimens ≥1 year apart, an inverted pattern was observed between the rates of change in LTL and WB mtDNA content per year, whereby faster decline of one was associated with the preservation of the other. Furthermore, if HIV viral control was not maintained between visits, increased rates of both LTL attrition and WB mtDNA loss were observed. We describe a novel relationship between two established aging markers, whereby rates of change in LTL and WB mtDNA are inversely related. Our findings highlight the importance of maintaining HIV viral control, the complementary longitudinal relationship between the two markers, and the need to consider both in aging studies.
| S-EPMC7467389 | biostudies-literature
Project description:In a graying world, there is an increasing interest in correlates of aging, especially those found in early life. Leukocyte telomere length (LTL) is an emerging marker of aging at the cellular level, but little is known regarding its link with poor decision making that often entails being overly impatient. Here we investigate the relationship between LTL and the degree of impatience, which is measured in the laboratory using an incentivized delay discounting task. In a sample of 1,158 Han Chinese undergraduates, we observe that steeper delay discounting, indexing higher degree of impatience, is negatively associated with LTL. The relationship is robust after controlling for health-related variables, as well as risk attitude-another important determinant of decision making. LTL in females is more sensitive to impatience than in males. We then asked if genes possibly modulate the effect of impatient behavior on LTL. The oxytocin receptor gene (OXTR) polymorphism rs53576, which has figured prominently in investigations of social cognition and psychological resources, and the estrogen receptor ? gene (ESR2) polymorphism rs2978381, one of two gonadal sex hormone genes, significantly mitigate the negative effect of impatience on cellular aging in females. The current results contribute to understanding the relationship between preferences in decision making, particularly impatience, and cellular aging, for the first time to our knowledge. Notably, oxytocin and estrogen receptor polymorphisms temper accelerated cellular aging in young females who tend to make impatient choices.
| S-EPMC4790989 | biostudies-literature
Project description:Telomere length is a marker of biological aging. Short leukocyte telomere length has been associated with various conditions including cardiovascular disorders. Here, we evaluated if patients with hypertrophic cardiomyopathy have altered leukocyte telomere length and whether this is associated with disease severity. A quantitative polymerase chain reaction-based method was used to measure peripheral blood leukocyte telomere length in 59 healthy control subjects and a well-characterized cohort of 88 patients diagnosed with hypertrophic cardiomyopathy: 32 patients with non-obstructive cardiomyopathy (HNCM) and 56 patients with obstructive cardiomyopathy (HOCM). We observed shorter leukocyte telomeres in both HNCM and HOCM patients compared to healthy controls. Furthermore, leukocyte telomere length was inversely associated with HCM even after adjusting for age and sex. Telomere length of HOCM patients was also inversely correlated with left ventricular outflow tract obstruction. Therefore, HOCM patients were categorized by tertiles of telomere length. Patients in the first tertile (shortest telomeres) had a significantly increased left ventricular posterior wall thickness at end-diastole and higher left ventricular outflow tract gradients, whereas the left ventricular end-diastolic diameter was lower compared with patients in the second and third tertile. In summary, telomere length is associated with the severity of the disease in the HOCM subtype.
| S-EPMC6060137 | biostudies-literature