Family Financial Pressure in Childhood and Telomere Length in Early Adolescence: A Prospective Study.

Much research on children in high-risk environments has focused on the biological consequences of maltreatment, adversity, and trauma. Whether other early-life stress sources such as family financial hardship are implicated in the cellular mechanism of disease development remains unclear. This study investigated the long-term effect of childhood exposure to family financial pressure on telomere length. It involved two waves of data collection occurring when participants reached Grade 3 (W1) and 7 (W2), respectively. In W1, parents reported family demographics and perceived financial stressors and pressure. In W2, participants provided buccal swab samples for measurement of their telomere length. Data from 92 participants (Mage in W2 = 13.2 years; 56.5% male) were analyzed. The main type of stressors reported by parents who perceived high family financial pressure in W1 were child-level stressors including affordability of their medical and educational expenses. Participants exposed to high parent-perceived family financial pressure in W1 had shorter telomeres in W2 when compared to those exposed to low parent-perceived family financial pressure (ß = -0.61, p = 0.042). Subgroup analyses revealed stronger associations in girls than boys. These findings reveal an important spillover effect between parental financial perceptions and stress and children's health at the cellular level.

Telomere dynamics in relation to experimentally increased locomotion costs and fitness in great tits.

Evidence that telomere length (TL) and dynamics can be interpreted as proxy for 'life stress' experienced by individuals stems largely from correlational studies. We tested for effects of an experimental increase of workload on telomere dynamics by equipping male great tits (Parus major) with a 0.9 g backpack for a full year. In addition, we analysed associations between natural life-history variation, TL and TL dynamics. Carrying 5% extra weight for a year did not significantly accelerate telomere attrition. This agrees with our earlier finding that this experiment did not affect survival or future reproduction. Apparently, great tit males were able to compensate behaviourally or physiologically for the increase in locomotion costs we imposed. We found no cross-sectional association between reproductive success and TL, but individuals with higher reproductive success (number of recruits) lost fewer telomere base pairs in the subsequent year. We used the TRF method to measure TL, which method yields a TL distribution for each sample, and the association between reproductive success and telomere loss was more pronounced in the higher percentiles of the telomere distribution, in agreement with the higher impact of ageing on longer telomeres within individuals. Individuals with longer telomeres and less telomere shortening were more likely to survive to the next breeding season, but these patterns did not reach statistical significance. Whether successful individuals are characterized by losing fewer or more base pairs from their telomeres varies between species, and we discuss aspects of ecology and social organisation that may explain this variation.

Why women may live longer than men do? A telomere-length regulated and diet-based entropic assessment.

BACKGROUND & AIMS: Empirical analyses of the data available around the word concluded that women have longer life span now, when compared to the men. Available literature unfortunately could not offer full answers to this observation. The "entropic age" concept suggests that ageing related changes in the body, such as loss of molecular functions and overwhelming of the maintenance systems, may be explained in terms of entropy generation. METHODS: Telomere-length regulated entropic assessment based on metabolic activity with four different diets carried out. RESULTS: Estimates of the life expectancy of the women on all of these diets is longer than those of the men. Faster shortening of the telomere lengths in men was the major reason of the shorter life expectancy. The highest and the lowest life expectancy for women were estimated with Mediterranean and the vegetarian diets, respectively; men were estimated to have the longest life span with the vegetarian diet and the shortest life span with the ketogenic diet. CONCLUSIONS: A higher rate of metabolism causes higher entropy generation and hints correlations that can be helpful in future ageing research. Faster shortening of the telomere lengths in men was the major reason of the estimation of the shorter life span for men.

From organ to cell: Multi-level telomere length assessment in patients with idiopathic pulmonary fibrosis.

RATIONALE: A subset of patients with idiopathic pulmonary fibrosis (IPF) contains short leukocyte telomeres or telomere related mutations. We previously showed that alveolar type 2 cells have short telomeres in fibrotic lesions. Our objectives were to better understand how telomere shortening associates with fibrosis in IPF lung and identify a subset of patients with telomere-related disease. METHODS: Average telomere length was determined in multiple organs, basal and apical lung, and diagnostic and end-stage fibrotic lung biopsies. Alveolar type 2 cells telomere length was determined in different areas of IPF lungs. RESULTS: In IPF but not in controls, telomere length in lung was shorter than in other organs, providing rationale to focus on telomere length in lung. Telomere length did not correlate with age and no difference in telomere length was found between diagnostic and explant lung or between basal and apical lung, irrespective of the presence of a radiological apicobasal gradient or fibrosis. Fifteen out of 28 IPF patients had average lung telomere length in the range of patients with a telomerase (TERT) mutation, and formed the IPFshort group. Only in this IPFshort and TERT group telomeres of alveolar type 2 cells were extremely short in fibrotic areas. Additionally, whole exome sequencing of IPF patients revealed two genetic variations in RTEL1 and one in PARN in the IPFshort group. CONCLUSIONS: Average lung tissue telomere shortening does not associated with fibrotic patterns in IPF, however, approximately half of IPF patients show excessive lung telomere shortening that is associated with pulmonary fibrosis driven by telomere attrition.

Comparison of flow-FISH and MM-qPCR telomere length assessment techniques for the screening of telomeropathies.

Assessment of telomere length (TL) in peripheral blood leukocytes is part of the diagnostic algorithm applied to patients with acquired bone marrow failure syndromes (BMFSs) and dyskeratosis congenita (DKC). Monochrome multiplex-quantitative polymerase chain reaction (MM-qPCR) and fluorescence in situ hybridization (flow-FISH) are methodologies available for TL screening. Dependent on TL expressed in relation to percentiles of healthy controls, further genetic testing for inherited mutations in telomere maintenance genes is recommended. However, the correct threshold to trigger this genetic workup is still under debate. Here, we prospectively compared MM-qPCR and flow-FISH regarding their capacity for accurate identification of DKC patients. All patients (n = 105) underwent genetic testing by next-generation sequencing and in 16 patients, mutations in DKC-relevant genes were identified. Whole leukocyte TL of patients measured by MM-qPCR was found to be moderately correlated with lymphocyte TL measured by flow-FISH (r² = 0.34; P < 0.0001). The sensitivity of both methods was high, but the specificity of MM-qPCR (29%) was significantly lower compared with flow-FISH (58%). These results suggest that MM-qPCR of peripheral blood cells is inferior to flow-FISH for clinical routine screening for suspected DKC in adult patients with BMFS due to lower specificity and a higher rate of false-positive results.

Successful aging, cognitive function, socioeconomic status, and leukocyte telomere length.

In a rapidly greying world, the notion that some individuals maintain successful aging trajectories, viz. high physical, cognitive, emotional, and social functioning in older age, is increasingly germane. Biomarkers of such successful aging are increasingly sought. Leukocyte telomere length (LTL), an emerging yardstick of cellular aging that is influenced by but distinct from chronological age, may also be associated to successful aging. Furthermore, given that socio-economic status (SES) influences successful aging trajectories, socioeconomic status may also moderate the association between chronological age and LTL. The goals of this study are to examine 1) whether successful aging is associated with LTL; 2) whether successful aging accounts for age-related LTL and 3) whether SES moderates the effect of age on LTL. Singaporean Chinese (n = 353) aged 65-80 completed a multidimensional assessment of successful aging and provided blood samples for LTL analysis. Results show that LTL negatively correlates with chronological age and positively correlates with successful aging. Successful aging mediates the association between chronological age and LTL. Moderated mediation analyses show that lower SES is associated with stronger negative associations of chronological age with successful aging and LTL. Moreover, the cognitive functioning dimension of successful aging is uniquely associated with LTL and its association with chronological age is moderated by SES. This study provides evidence that among older Singaporean Chinese with lower SES, declines in successful aging and in cognitive functioning are linked to age-related LTL shortening and hence to accelerated aging at the cellular level.

Lifecourse Adversity and Telomere Length in Older Women from Northeast Brazil.

We examined associations between adverse childhood experiences (ACEs) and shorter telomere length (TL) in 83 older women, including 42 women with less than secondary education and 41 with secondary or more education in a city of Northeast Brazil, a region with substantial socioeconomic inequalities. The low education sample was selected from a representative survey at local neighborhood health centers, while the high education group consisted of a convenience sample recruited by advertising in community centers and centers affiliated with the local university. Relative leukocyte TL was measured by quantitative polymerase chain reaction from blood samples. ACEs were self-reported. Spline linear regression was fitted to assess the strength of the associations between ACEs and TL. Among women with low education, median TL was 1.02 compared with 0.64 in the high education group (p = 0.0001). Natural log-transformed T/S ratio as the dependent variable was used in analysis. Women with low education had been exposed to more ACEs, and among them those experiencing two or more ACEs had longer TL than women exposed to ≤1 ACEs (p = 0.03); among women with high education, this difference was not significant (p = 0.49). In analyses adjusted by age, education, and parental abuse of alcohol, the linear trend of higher TL with increasing ACEs was confirmed (p = 0.02), and the mean difference in TL between groups remained significant (p = 0.002). The unexpected positive relationship between low education and ACEs with TL suggests that older adults who have survived harsh conditions prevailing in Northeast Brazil have the longest TL of their birth cohort.

Paired assessment of liver telomere lengths in hepatocellular cancer is a reliable predictor of disease persistence.

In the present study, we used a small series of highly defined patients, where we had matched timed peripheral blood samples (PBS), as well as paired liver biopsies obtained during collection of blood samples from patients with diagnosed hepatocellular carcinoma (HCC) and compared the correlation between the changes of telomere lengths in these defined samples. Patients included had either HCC alone or in conjunction with either pre-existing hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. PCR-based assay incorporating primers to the telomeric hexamer repeats to polymerize and detect telomeric DNA was used. The average telomere length for each independent assessment was measured by seeing the differences in the intensity of the sample's telomere signal (T) to the signal from a single-copy gene (S-, ß-globin) to estimate the standard ratio. Our results provide the first convincing evidence that PBS may be utilized to assay telomere shortening as a predictor for disease persistence in HCC resulting after HBV or HCV infection, but not in non-infectious cause-stimulated HCC. These findings provide incipient opportunity to develop telomere length assessment as a biomarker tool for prediction of HCC in patients with HBV or HCV infection, as well as to gauge responses to chemotherapy and other treatment modalities.

Race-related health disparities and biological aging: does rate of telomere shortening differ across blacks and whites?

Recent work suggests that leukocyte telomere length (LTL), a marker of cellular aging, is sensitive to effects of social stress and may also provide early indication of premature aging. Using data from a birth cohort with LTL information at birth and in middle adulthood we examined a potential source of race-based health disparity by testing the hypothesis that Blacks would demonstrate a faster rate of telomere shortening than Whites. Linear regression analyses were conducted and adjusted for pack years, BMI, education and social factors, diet, exercise, marital status, and age. At birth black individuals had LTLs that were longer, on average, than their White counterparts (b=3.85, p<0.01). However, rate of shortening was greater for Blacks, who showed a larger difference in length between birth and adulthood (b=5.10, p=0.01) as compared with Whites, resulting in smaller racial differences in absolute adult LTL.