Leukocyte Telomere Length In Women Research Articles

Leukocyte telomere length in women with multiple sclerosis: Comparison with healthy women during pregnancy and puerperium

ObjectivesSeveral studies indicated leukocyte telomere length (LTL) as a biomarker of multiple sclerosis (MS) evolution. This study aimed to investigate LTL in women with multiple sclerosis (MS) compared to that in healthy women (HW) across different reproductive phases, and to evaluate its relationship with MS activity. MethodsBlood samples were collected from women with MS and HW during the fertile phase, pregnancy, and puerperium. LTL was determined using quantitative fluorescence in situ hybridization (Q-FISH). ResultsBlood samples from 68 women with MS (22 during fertile life, 23 during pregnancy, and 23 post-partum) and 52 HW (23 during fertile life, 20 during pregnancy, and 9 post-partum) were analyzed. During pregnancy, LTL in MS women and HW was 84.7 ± 10.5 and 77.6 ± 11.5, respectively (p < 0.005). Regression analysis showed that shorter LTL was associated with pregnancy in HW (p = 0.021); this relationship was not observed in MS women, for whom shorter LTL was related to a higher EDSS (p = 0.036). A longitudinal analysis was performed in eight MS women, showing LTL shortening from pregnancy to puerperium (p = 0.003), which was related to MS reactivation (p = 0.042). ConclusionOur results highlight the possible associations between LTL, reproductive biological phases, and MS activity after delivery.

Personal exposure to NO2 and benzene in the Cape Town region of South Africa is associated with shorter leukocyte telomere length in women

Air pollution exposure is a major global health concern and has been associated with molecular aging. Unfortunately, the situation has not received much attention in the African region. The aim of this study was to investigate whether current personal ambient NO2 and benzene, toluene, ethyl-benzene and xylenes (ortho (o)-, meta (m)- and para (p)-xylene (BTEX) exposure is associated with leukocyte telomere length (LTL), a marker of molecular ageing, in apparently healthy women (mean ± SD age: 42.5 ± 13.4 years) residing in the Cape Town region of South Africa. The repeated measures study collected data from 61 women. Seven-day median (interquartile range (IQR)) personal NO2 and BTEX exposure levels were determined via compact passive diffusion samplers carried on the person prior to baseline (NO2: 14.2 (9.4–17.2) μg/m³; Benzene: 3.1 (2.1–5.3) μg/m³) and 6-month follow-up (NO2: 10.6 (6.6–13.6) μg/m³; Benzene: 2.2 (1.3–4.9) μg/m³) visits. LTL was measured at baseline and follow-up using a real-time PCR method. Multiple linear mixed model analyses (adjusting for age, body mass index, smoking, employment status, level of education and assessment visit) showed that each IQR increment increase in NO2 (7.0 μg/m³) and benzene (3.3 μg/m³) was associated with −7.30% (95% CI: −10.98 to −3.46%; p < 0.001) and −6.78% (95% CI: −11.88 to −1.39%; p = 0.015) difference in LTL, respectively. The magnitude of these effects of NO2 and benzene corresponds to the effect of an increase of 10.3- and 6.0-year in chronological age on LTL. Our study shows that personal exposures to NO2 and benzene are associated with molecular ageing as indicated by LTL in healthy women residing in the Cape Town region.

Leukocyte telomere length as an aging marker and risk factor for human age-related diseases

Leukocyte telomere length (LTL) associations with age, sex, and risk factors for age-related diseases have been studied in Russian people of preretirement and retirement age. This parameter has been determined by quantitative real-time PCR in 398 men (56.3 ± 7.2 years) and 365 women (56.6 ± 7.1 years) selected from a population sample of 45 to 69-year-old residents of the Oktyabrskii and Kirovskii raions of Novosibirsk (9400 people). The sample was formed in the course of the international project HAPIEE. Telomere length has been found to correlate with age (r =–0.159, p < 0.001) and the waist: hip ratio (WHR) (r =–0.107, p = 0.003). The average LTL in women is significantly greater than in men, p = 0.031. In men, LTL correlates with body mass (r = 0.140, p = 0.005) and waist size (r = 0.111, p = 0.027). In women, there are inverse correlations of LTL with waist size (r =–0.127, p = 0.015) and WHR (r =–0.141, p = 0.007). Leukocyte telomere length inversely correlates with the amount smoked (r =–0.121, р = 0.024). It directly correlates with age, smoking, and a variety of phenotypical traits. In men with family histories of malignancies, LTL is greater than in men without such histories.

Associations of Accelerometer-Measured and Self-Reported Sedentary Time With Leukocyte Telomere Length in Older Women.

Few studies have assessed the association of sedentary time with leukocyte telomere length (LTL). In a cross-sectional study conducted in 2012-2013, we examined associations of accelerometer-measured and self-reported sedentary time with LTL in a sample of 1,481 older white and African-American women from the Women's Health Initiative and determined whether associations varied by level of moderate- to vigorous-intensity physical activity (MVPA). The association between sedentary time and LTL was evaluated using multiple linear regression models. Women were aged 79.2 (standard deviation, 6.7) years, on average. Self-reported sedentary time was not associated with LTL. In a model adjusting for demographic characteristics, lifestyle behaviors, and health-related factors, among women at or below the median level of accelerometer-measured MVPA, those in the highest quartile of accelerometer-measured sedentary time had significantly shorter LTL than those in the lowest quartile, with an average difference of 170 base pairs (95% confidence interval: 4, 340). Accelerometer-measured sedentary time was not associated with LTL in women above the median level of MVPA. Findings suggest that, on the basis of accelerometer measurements, higher sedentary time may be associated with shorter LTL among less physically active women.

Genetic variants within telomere-associated genes, leukocyte telomere length and the risk of acute coronary syndrome in Czech women

The association between leukocyte telomere length (LTL) and cardiovascular disease (CVD) has been published in many reports, although almost exclusively in men. In our study we analysed the association between LTL and five selected variants within three candidate genes (TERC rs12696304; TERF2IP rs3784929 and rs8053257; UCP2 rs659366 and rs622064), which are not only involved in telomere-length maintenance but also potentially associated with higher risk of acute coronary syndrome (ACS) in Czech women (505 cases and 642 controls). We detected significantly shorter LTL in women with ACS (P<0.001), but the difference disappeared after multiple adjustments. We did not find any significant associations between analysed variants and LTL, except for rs622064 within the UCP2 gene, in which case AA homozygotes had a higher LTL (P<0.04). Genotype frequencies of the analysed SNPs did not differ between controls and women with ACS. Variants within UCP2 (rs622064; CC vs. A allele carriers OR=1.61; 95% CI: 1.21–2.15, P<0.002) and within TERF2IP (rs8053257; A allele carriers vs. GG, OR=1.78; 95% CI: 1.07–3.18, P<0.03) were associated with increased risk of type 2 diabetes mellitus (T2DM). Analysed polymorphisms were not major determinants of telomere length or ACS risk in Czech females.

Leukocyte telomere length and its association with mammographic density and proliferative diagnosis among women undergoing diagnostic image-guided breast biopsy.

BackgroundElevated mammographic density (MD) is a strong breast cancer risk factor but the mechanisms underlying the association are poorly understood. High MD and breast cancer risk may reflect cumulative exposures to factors that promote epithelial cell division. One marker of cellular replicative history is telomere length, but its association with MD is unknown. We investigated the relation of telomere length, a marker of cellular replicative history, with MD and biopsy diagnosis.MethodsOne hundred and ninety-five women, ages 40–65, were clinically referred for image-guided breast biopsies at an academic facility in Vermont. Relative peripheral blood leukocyte telomere length (LTL) was measured using quantitative polymerase chain reaction. MD volume was quantified in cranio-caudal views of the breast contralateral to the primary diagnosis in digital mammograms using a breast density phantom, while MD area (cm2) was measured using thresholding software. Associations between log-transformed LTL and continuous MD measurements (volume and area) were evaluated using linear regression models adjusted for age and body mass index. Analyses were stratified by biopsy diagnosis: proliferative (hyperplasia, in-situ or invasive carcinoma) or non-proliferative (benign or other non-proliferative benign diagnoses).ResultsMean relative LTL in women with proliferative disease (n = 141) was 1.6 (SD = 0.9) vs. 1.2 (SD = 0.6) in those with non-proliferative diagnoses (n = 54) (P = 0.002). Mean percent MD volume did not differ by diagnosis (P = 0.69). LTL was not associated with MD in women with proliferative (P = 0.89) or non-proliferative (P = 0.48) diagnoses. However, LTL was associated with a significant increased risk of proliferative diagnosis (adjusted OR = 2.46, 95 % CI: 1.47, 4.42).ConclusionsOur analysis of LTL did not find an association with MD. However, our findings suggest that LTL may be a marker of risk for proliferative pathology among women referred for biopsy based on breast imaging.

Multiple measures of adiposity are associated with mean leukocyte telomere length in the northern Finland birth cohort 1966.

Studies of leukocyte telomere length (LTL) and adiposity have produced conflicting results, and the relationship between body mass index (BMI) and telomere length throughout life remains unclear. We therefore tested association of adult LTL measured in 5,598 participants with: i) childhood growth measures (BMI and age at adiposity rebound (AR)); ii) change in BMI from childhood to adulthood and iii) adult BMI, waist-to-hip ratio (WHR), body adiposity index (BAI). Childhood BMI at AR was positively associated with LTL at 31 years in women (P = 0.041). Adult BMI and WHR in both men (P = 0.025 and P = 0.049, respectively) and women (P = 0.029 and P = 0.008, respectively), and BAI in women (P = 0.021) were inversely associated with LTL at 31 years. An increase in standardised BMI between early childhood and adulthood was associated with shorter adult LTL in women (P = 0.008). We show that LTL is inversely associated with multiple measures of adiposity in both men and women. Additionally, BMI increase in women from childhood to adulthood is associated with shorter telomeres at age 31, potentially indicating accelerated biological ageing.

Comparison Between Southern Blots and qPCR Analysis of Leukocyte Telomere Length in the Health ABC Study

Only a few studies, primarily limited to small samples, have examined the relationship between leukocyte telomere length (LTL) data generated by Southern blots, expressed in kilobases, versus quantitative PCR data, expressed in the telomere product/a single gene product (T/S). In the present study, we compared LTL data generated by the two methods in 681 elderly participants (50% African Americans, 50% of European origin, 49.2% women, mean age 73.7±2.9 years) in the Health Aging and Body Composition Study. The correlation between the data generated by the two methods was modest (R (2) = .27). Both methods captured the age effect on LTL and the longer LTL in women than in men. However, only the Southern blot method showed a significantly longer LTL in African Americans than in European decent individuals, which might be attributed to the larger measurement error of the quantitative PCR-based method than the Southern blots.

Pain Is Associated With Short Leukocyte Telomere Length in Women With Fibromyalgia

Telomere length, considered a measure of biological aging, is linked to morbidity and mortality. Psychosocial factors associated with shortened telomeres are also common in chronic pain; yet, little is known about telomere length in pain populations. Leukocyte telomere length was evaluated in 66 women with fibromyalgia and 22 healthy female controls. Participants completed questionnaires and a subgroup of fibromyalgia patients underwent quantitative sensory testing (QST; n = 12) and neuroimaging (n = 12). Telomere length was measured using the quantitative polymerase chain reaction method. Although patients had shorter telomere length than controls, the difference was not statistically significant. However, higher levels of pain within fibromyalgia were associated with shorter telomere length (P = .039). When pain and depression were combined, patients categorized as high-pain/high-depression had an age-adjusted telomere length 265 base pairs shorter than those with low-pain/low-depression (P = .043), a difference consistent with approximately 6 years of chronological aging. In the subset tested, telomere length was also related to pain threshold and pain sensitivity, as well as gray matter volume, such that patients with shorter telomeres were more sensitive to evoked pain and had less gray matter in brain regions associated with pain processing (eg, primary somatosensory cortex). These preliminary data support a relationship between pain and telomere length. PerspectiveOur findings support a link between premature cellular aging and chronic pain. These preliminary data imply that chronic pain is a more serious condition than has typically been recognized in terms of bodily aging.

High Phobic Anxiety Is Related to Lower Leukocyte Telomere Length in Women

BackgroundChronic psychological distress has been linked to shorter telomeres, an indication of accelerated aging. Yet, little is known about relations of anxiety to telomeres. We examined whether a typically chronic form of anxiety – phobic anxiety – is related to telomere length.Methodology/Principal FindingsRelative telomere lengths (RTLs) in peripheral blood leukocytes were measured by quantitative real-time polymerase chain reaction among 5,243 women (aged 42–69 years) who: were participants in the Nurses' Health Study; were controls in prior case-control studies of telomeres and disease, or randomly selected healthy participants in a cognitive function sub-study; had completed the Crown-Crisp phobic index proximal to blood collection. Adjusted least-squares mean RTLs (z-scores) were calculated across phobic categories. Higher phobic anxiety was generally associated with lower RTLs (age-adjusted p-trend = 0.09); this association was similar after adjustment for confounders – paternal age-at-birth, smoking, body mass index (BMI) and physical activity (p-trend = 0.15). Notably, a threshold was identified. Among women with Crown-Crisp<6 points, the multivariable-adjusted least-squares mean RTL z-score = 0.02 standard units; however, among the most phobic women (Crown-Crisp≥6), the multivariable-adjusted least-squares mean RTL z-score = −0.09 standard units (mean difference = −0.10 standard units; p = 0.02). The magnitude of this difference was comparable to that for women 6 years apart in age. Finally, effect modification by BMI, smoking and paternal age was observed: associations were stronger among highly phobic women with BMI≥25 kg/m2, without smoking history, or born to fathers aged ≥40 years.Conclusions/SignificanceIn this large, cross-sectional study high phobic anxiety was associated with shorter telomeres. These results point toward prospective investigations relating anxiety to telomere length change.

Pain is associated with short leukocyte telomere length in women with fibromyalgia

Pain is associated with short leukocyte telomere length in women with fibromyalgia

Pain is associated with short leukocyte telomere length in women with fibromyalgia

Telomere length is considered a marker of biological aging that is linked to an increased risk for morbidity and mortality. Psychosocial factors (e.g., depression, anxiety, obesity, trauma) are associated with shortened telomeres; factors all common in chronic pain. The objective of this study was to evaluate the role of pain in leukocyte telomere length in 66 women with fibromyalgia and 22 healthy female controls. Participants completed questionnaires and a subgroup of fibromyalgia patients underwent quantitative sensory testing (QST; n=12) and neuroimaging (voxel-based morphometry; n=12).

Physical Activity, Sedentary Behavior, and Leukocyte Telomere Length in Women

Leukocyte telomere length (LTL) is a potential indicator of cellular aging; however, its relation to physical activity and sedentary behavior is unclear. The authors examined cross-sectionally associations among activity, sedentary behavior, and LTL among 7,813 women aged 43-70 years in the Nurses' Health Study. Participants self-reported activity by questionnaire in 1988 and 1992 and sedentary behavior in 1992. Telomere length in peripheral blood leukocytes, collected in 1989-1990, was measured by quantitative polymerase chain reaction. The least-squares mean telomere length (z-score) was calculated after adjustment for age and other potential confounders. For total activity, moderately or highly active women had a 0.07-standard deviation (SD) increase in LTL (2-sided P(trend) = 0.02) compared with those least active. Greater moderate- or vigorous-intensity activity was also associated with increased LTL (SD = 0.11 for 2-4 vs. <1 hour/week and 0.04 for ≥7 vs. <1 hour/week; 2-sided P(trend) = 0.02). Specifically, calisthenics or aerobics was associated with increased LTL (SD = 0.10 for ≥2.5 vs. 0 hours/week; 2-sided P(trend) = 0.04). Associations remained after adjustment for body mass index. Other specific activities and sitting were unassociated with LTL. Although associations were modest, these findings suggest that even moderate amounts of activity may be associated with longer telomeres, warranting further investigation in large prospective studies.

Educational attainment and mean leukocyte telomere length in women in the European Prospective Investigation into Cancer (EPIC)-Norfolk population study.

Telomere length has been postulated as a marker of biological aging. Recent evidence has suggested that educational attainment but not social class is associated with telemore length. We investigated the associations between educational attainment, social class and relative mean telomere length in an ethnically homogeneous population of 4441 women, aged 41-80 years. Mean telomere length was measured using high-throughput quantitative Real Time PCR. Educational attainment (p=0.015) but not social class (p=0.61) was associated with mean telomere length in these data. This association was independent of social class and of systolic blood pressure, high-density lipoprotein cholesterol, cigarette smoking, body mass index, glycated hemoglobin, plasma vitamin C and physical activity (p=0.014), and was not attenuated through additional adjustment for measures of social adversity, including those experienced during childhood (p=0.006). Our results, at least for women, provide support for the findings previously reported in this journal that lower educational attainment, but not social class, is associated with shorter telomere length.

Abstract B112: Physical activity, sedentary behavior, and leukocyte telomere length in women

Abstract Telomeres are repetitive DNA-protein complexes that protect the ends of linear chromosomes and maintain genomic stability. They undergo erosion with each cycle of cell division, and oxidative stress and inflammation accelerate this shortening. Critically short telomeres may lead to several processes implicated in carcinogenesis, including chromosomal degradation, end-to-end fusion, and atypical recombination. Telomere length in peripheral blood leukocytes (PBLs) is a potential indicator of cellular aging and shortened leukocyte telomere length (LTL) has been linked to an increased risk of various cancer types, such as bladder, lung, and renal-cell. Regular physical activity reduces the risk of developing many cancers, and studies have observed lower levels of oxidative stress and inflammation in regularly active individuals. However, few population-based studies have examined the relation between physical activity and LTL, and none has addressed sedentary behavior. In addition, information is scarce on the role of exercise intensity and type in this relation. The authors therefore examined cross-sectionally the association between physical activity, sedentary behavior, and LTL among 7,813 women ages 43–70 in the Nurses' Health Study. Participants self-reported activity by questionnaire in 1988 and 1992, and sedentary behavior in 1992. Telomere length in PBLs, collected in 1989–1990, was measured by quantitative polymerase chain reaction. Least squares mean telomere length (z-score) was calculated after adjustment for age and other potential confounders. Total activity was positively associated with LTL. Compared with the least active women, those moderately or highly active had a 0.07 standard deviation (SD) increase in LTL (p-trend=0.02), a difference corresponding on average to 4.4 years of aging. Greater moderate-or vigorous-intensity activity was also associated with increased LTL; women who exercised 2–4 hours per week, an amount corresponding to current US guidelines, had the longest telomeres (0.11 SD increase for 2–4 vs. &amp;lt;1 hours/week; 0.04 SD increase for 7+ vs. &amp;lt;1 hours/week; p-trend=0.02). Among the individual activities, greater calisthenics or aerobics was associated with longer telomeres (0.10 SD increase for &amp;gt;2.5 vs. 0 hours/week; p-trend=0.04). Associations remained after additionally adjusting for body mass index. Time spent on other activities and time spent sitting were unassociated with LTL. Although associations were modest, these findings suggest that even moderate amounts of activity may be associated with longer telomeres, providing insight into the understanding of how exercise may influence cancer risk on the cellular level. These findings warrant further investigation in large prospective studies. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B112.

Associations between diet, lifestyle factors, and telomere length in women

Leukocyte telomere length is associated with diseases of aging, but there is limited knowledge of diet and lifestyle determinants. The objective was to examine cross-sectionally the association between diet, body composition, and lifestyle factors on leukocyte telomere length in women. Leukocyte telomere length was measured by quantitative polymerase chain reaction in 2284 female participants from the Nurses' Health Study, who were selected as controls for an investigation of biological predictors of cancer. Diet, lifestyle, and anthropometric data were assessed by questionnaire. After multivariate adjustment, dietary fiber intake was positively associated with telomere length (z score), specifically cereal fiber, with an increase of 0.19 units between the lowest and highest quintiles (P = 0.007, P for trend = 0.03). Although total fat intake was not associated with telomere length, polyunsaturated fatty acid intake (-0.26 units, quintile 5 compared with quintile 1: P = 0.002, P for trend = 0.02), specifically linoleic acid intake, was inversely associated with telomere length after multivariate adjustment (-0.32 units; P = 0.001, P for trend = 0.05). Waist circumference was inversely associated with telomere length [0.15-unit difference in z score in a comparison of the highest (> or = 32 in, 81.28 cm) with the lowest (< or = 28 in, 71.12 cm) category (P = 0.01, P for trend = 0.02) in the multivariate model]. We found no association between telomere length and smoking, physical activity, or postmenopausal hormone use. Although the strength of the associations was modest in this population of middle- and older-age women, our results support the hypothesis that body composition and dietary factors are related to leukocyte telomere length, which is a potential biomarker of chronic disease risk.

Leukocyte telomere length is associated with measures of subclinical atherosclerosis

AimsOur aim was to test the association of mean leukocyte telomere length (LTL) with ultrasonic measures of subclinical atherosclerosis such as intima-media thickness in the common carotid (IMTcc) and sum of plaque areas (SPA) and with serological markers. Methods and resultsCarotid and femoral bifurcations were scanned in 762 general population volunteers (46% men) over 40. Four features were considered: (a) IMTcc, (b) sum plaque areas of carotid plaques (SPAcar), (c) sum plaque area of common femoral plaques (SPAfem) and (d) sum plaque area (SPA – sum of the plaque areas of the largest plaques present in each of both carotid and femoral bifurcations). Mean LTL was determined with a quantitative real-time PCR-based method. IMTcc was strongly associated with mean LTL both before and after correction for traditional risk factors (B= −0.002; 95% CI=−0.004 to −0.00; p=0.014). In sex-specific analysis, the association was stronger in men (p for sex interaction<0.001). SPAfem was associated with LTL in women before and after correction (B=−0.195; 95% CI=−0.38 to −0.01; p=0.037) (p for sex interaction<0.001). LTL was also associated with age and sex-adjusted levels of hsCRP (p=0.012), sCD40L (p=0.042), homocysteine (p=0.006), creatinine (p=0.02), ApoA1 (p=0.01), Lp(a) (p=0.04) and HOMA-IR (p=0.008). ConclusionsOur results support the telomere hypothesis and highlight potential differences in the biological mechanisms leading to intima-media thickening and/or plaque formation between vascular beds. They may provide insights into a novel treatment of antisenescence to prevent atherosclerosis.

Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women

Background: Vitamin D is a potent inhibitor of the proinflammatory response and thereby diminishes turnover of leukocytes. Leukocyte telomere length (LTL) is a predictor of aging-related disease and decreases with each cell cycle and increased inflammation.Objective: The objective of the study was to examine whether vitamin D concentrations would attenuate the rate of telomere attrition in leukocytes, such that higher vitamin D concentrations would be associated with longer LTL.Design: Serum vitamin D concentrations were measured in 2160 women aged 18–79 y (mean age: 49.4) from a large population-based cohort of twins. LTL was measured by using the Southern blot method.Results: Age was negatively correlated with LTL (r = −0.40, P < 0.0001). Serum vitamin D concentrations were positively associated with LTL (r = 0.07, P = 0.0010), and this relation persisted after adjustment for age (r = 0.09, P < 0.0001) and other covariates (age, season of vitamin D measurement, menopausal status, use of hormone replacement therapy, and physical activity; P for trend across tertiles = 0.003). The difference in LTL between the highest and lowest tertiles of vitamin D was 107 base pairs (P = 0.0009), which is equivalent to 5.0 y of telomeric aging. This difference was further accentuated by increased concentrations of C-reactive protein, which is a measure of systemic inflammation.Conclusion: Our findings suggest that higher vitamin D concentrations, which are easily modifiable through nutritional supplementation, are associated with longer LTL, which underscores the potentially beneficial effects of this hormone on aging and age-related diseases.