Different epigenetic signatures of newborn telomere length and telomere attrition rate in early life.
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ABSTRACT:
SUBMITTER: Wang C
PROVIDER: S-EPMC8221291 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Longitudinal studies have sought to establish whether environmental exposures such as smoking accelerate the attrition of individuals' telomeres over time. These studies typically control for baseline telomere length (TL) by including it as a covariate in statistical models. However, baseline TL also differs between smokers and non-smokers, and telomere attrition is spuriously linked to baseline TL via measurement error and regression to the mean. Using simulated datasets, we show that controlling for baseline TL overestimates the true effect of smoking on telomere attrition. This bias increases with increasing telomere measurement error and increasing difference in baseline TL between smokers and non-smokers. Using a meta-analysis of longitudinal datasets, we show that as predicted, the estimated difference in telomere attrition between smokers and non-smokers is greater when statistical models control for baseline TL than when they do not, and the size of the discrepancy is positively correlated with measurement error. The bias we describe is not specific to smoking and also applies to other exposures. We conclude that to avoid invalid inference, models of telomere attrition should not control for baseline TL by including it as a covariate. Many claims of accelerated telomere attrition in individuals exposed to adversity need to be re-assessed.
| S-EPMC6837209 | biostudies-literature
Project description:BackgroundTelomere length (TL) is considered a biological marker of aging and may indicate age-related disease susceptibility. Adults and children show a fixed ranking and tracking of TL over time. However, the contribution of an individual's initial birth TL to their later life TL is unknown. We evaluated change and tracking of TL from birth to child- and adulthood.MethodsTelomere length at birth was measured using qPCR in two independent prospective birth cohorts. After a median follow-up period of 4 years in ENVIRONAGE (n = 273) we assessed leukocyte telomere length (LTL) and after 23 years in EFPTS (n = 164) buccal TL was assessed. Correlations and multivariable regression models were applied to study telomere tracking and determinants of TL change from birth onwards.FindingsIn children, LTL at the age of 4 correlates with TL at the start of life both in cord blood (r = 0.71, P < 0.0001;) and placenta (r = 0.60, P < 0.0001) and was -11.2% and -33.1% shorter, respectively. In adulthood, buccal TL at the age of 23 correlates with placental TL (r = 0.46, P < 0.0001) and was -35.9% shorter. TL attrition was higher in individuals with longer birth TL. However, based on TL ranking, individuals do not tend to change dramatically from TL rank after 4 or 23 years of follow-up. Finally, longer maternal TL associates with lower telomere attrition in the next generation.InterpretationThe high prediction of newborn TL for later life TL, and stable TL ranking from birth onwards underscores the importance of understanding the initial setting of newborn TL and its significance for later life.FundingEuropean Research Council (ERC-StG310898) and Flemish Scientific Fund (12X9620N).
| S-EPMC7808927 | biostudies-literature
Project description:The attrition of telomeres, the ends of eukaryote chromosomes, is thought to play an important role in cell deterioration with advancing age. The observed variation in telomere length among individuals of the same age is therefore thought to be related to variation in potential longevity. Studies of this relationship are hampered by the time scale over which individuals need to be followed, particularly in long-lived species where lifespan variation is greatest. So far, data are based either on simple comparisons of telomere length among different age classes or on individuals whose telomere length is measured at most twice and whose subsequent survival is monitored for only a short proportion of the typical lifespan. Both approaches are subject to bias. Key studies, in which telomere length is tracked from early in life, and actual lifespan recorded, have been lacking. We measured telomere length in zebra finches (n = 99) from the nestling stage and at various points thereafter, and recorded their natural lifespan (which varied from less than 1 to almost 9 y). We found telomere length at 25 d to be a very strong predictor of realized lifespan (P < 0.001); those individuals living longest had relatively long telomeres at all points at which they were measured. Reproduction increased adult telomere loss, but this effect appeared transient and did not influence survival. Our results provide the strongest evidence available of the relationship between telomere length and lifespan and emphasize the importance of understanding factors that determine early life telomere length.
| S-EPMC3277142 | biostudies-other
Project description:Early adversity, in the form of abuse, neglect, socioeconomic status and other adverse experiences, is associated with poor physical and mental health outcomes. To understand the biologic mechanisms underlying these associations, studies have evaluated the relationship between early adversity and telomere length, a marker of cellular senescence. Such results have varied in regard to the size and significance of this relationship. Using meta-analytic techniques, we aimed to clarify the relationship between early adversity and telomere length while exploring factors affecting the association, including adversity type, timing and study design. A comprehensive search in July 2016 of PubMed/MEDLINE, PsycINFO and Web of Science identified 2462 studies. Multiple reviewers appraised studies for inclusion or exclusion using a priori criteria; 3.9% met inclusion criteria. Data were extracted into a structured form; the Newcastle-Ottawa Scale assessed study quality, validity and bias. Forty-one studies (N=30 773) met inclusion criteria. Early adversity and telomere length were significantly associated (Cohen's d effect size=-0.35; 95% CI, -0.46 to -0.24; P<0.0001). Sensitivity analyses revealed no outlier effects. Adversity type and timing significantly impacted the association with telomere length (P<0.0001 and P=0.0025, respectively). Subgroup and meta-regression analyses revealed that medication use, medical or psychiatric conditions, case-control vs longitudinal study design, methodological factors, age and smoking significantly affected the relationship. Comprehensive evaluations of adversity demonstrated more extensive telomere length changes. These results suggest that early adversity may have long-lasting physiological consequences contributing to disease risk and biological aging.
| S-EPMC5608639 | biostudies-literature
Project description:Moods are enduring affective states that we hypothesise should be affected by an individual's developmental experience and its current somatic state. We tested whether early-life adversity, induced by manipulating brood size, subsequently altered juvenile European starlings' (Sturnus vulgaris) decisions in a judgment bias task designed to provide a cognitive measure of mood. We predicted that starlings from larger broods, specifically those that had experienced more nest competitors larger than themselves would exhibit reduced expectation of reward, indicative of a 'pessimistic', depression-like mood. We used a go/no-go task, in which 30 starlings were trained to probe a grey card disc associated with a palatable mealworm hidden underneath and avoid a different shade of grey card disc associated with a noxious quinine-injected mealworm hidden underneath. Birds' response latencies to the trained stimuli and also to novel, ambiguous stimuli intermediate between these were subsequently tested. Birds that had experienced greater competition in the nest were faster to probe trained stimuli, and it was therefore necessary to control statistically for this difference in subsequent analyses of the birds' responses to the ambiguous stimuli. As predicted, birds with more, larger nest competitors showed relatively longer latencies to probe ambiguous stimuli, suggesting reduced expectation of reward and a 'pessimistic', depression-like mood. However, birds with greater developmental telomere attrition--a measure of cellular aging associated with increased morbidity and reduced life-expectancy that we argue could be used as a measure of somatic state--showed shorter latencies to probe ambiguous stimuli. This would usually be interpreted as evidence for a more positive or 'optimistic' affective state. Thus, increased competition in the nest and poor current somatic state appear to have opposite effects on cognitive biases. Our results lead us to question whether increased expectation of reward when presented with ambiguous stimuli always indicates a more positive affective state. We discuss the possibility that birds in poor current somatic state may adopt a 'hungry' cognitive phenotype that could drive behaviour commonly interpreted as 'optimism' in food-rewarded cognitive bias tasks.
| S-EPMC4519284 | biostudies-literature
Project description:ObjectiveWe investigated the relationship between early life growth patterns and blood telomere length (TL) in adulthood using conditional measures of lean and fat mass growth to evaluate potentially sensitive periods of early life growth.MethodsThis study included data from 1562 individuals (53% male; age 20-22 years) participating in the Cebu Longitudinal Health and Nutrition Survey, located in metropolitan Cebu, Philippines. Primary exposures included length-for-age z-score (HAZ) and weight-for-age z-score (WAZ) at birth and conditional measures of linear growth and weight gain during four postnatal periods: 0-6, 6-12, and 12-24 months, and 24 months to 8.5 years. TL was measured at ~21 years of age. We estimated associations using linear regression.ResultsThe study sample had an average gestational age (38.5 ± 2 weeks) and birth size (HAZ = -0.2 ± 1.1, WAZ = -0.7 ± 1.0), but by age 8.5 years had stunted linear growth (HAZ = -2.1 ± 0.9) and borderline low weight (WAZ = -1.9 ± 1.0) relative to World Health Organization references. Heavier birth weight was associated with longer TL in early adulthood (P = .03), but this association was attenuated when maternal age at birth was included in the model (P = .07). Accelerated linear growth between 6 and 12 months was associated with longer TL in adulthood (P = .006), whereas weight gain between 12 and 24 months was associated with shorter TL in adulthood (P = .047).ConclusionsIn Cebu, individuals who were born heavier have longer TL in early adulthood, but that birthweight itself may not explain the association. Findings suggest that childhood growth is associated with the cellular senescence process in adulthood, implying early life well-being may be linked to adult health.
| S-EPMC6872908 | biostudies-literature
Project description:The newborn setting of leukocyte telomere length (LTL) likely has important implications for telomere dynamics over the lifespan. However, its determinants are poorly understood. Hormones play an important role during pregnancy and delivery. We hypothesized that exposure to hormones may impact the fetal telomere biology system. To test this hypothesis, cortisol, estradiol, dehydroepiandrosterone sulfate (DHEAS) and reactive oxygen species (ROS) were measured in cord blood of 821 newborns from a prospective study. After accounting for the effects of potential determinants of newborn LTL, a 10-fold increase in DHEAS concentration was associated with a 0.021 increase in T/S ratio of newborn LTL (95% confidence interval: 0.009-0.034, P?=?0.0008). For newborns who fell in the lowest quartile of DHEAS level, the mean newborn LTL was estimated to be approximately 2.0% shorter than the newborns in the highest DHEAS concentration quartile (P?=?0.0014). However, no association was found between newborn LTL and cortisol or estradiol. As expected, newborns with higher ROS level (ROS?>?260?mol/L) had lower LTL compared to that with lower ROS level (ROS???260?mol/L) (P?=?0.007). There was also an inverse relationship between DHEAS and ROS (P?<?1×10-4). Our findings suggest that exposure to DHEAS may exert a "programming" effect on the newborn telomere biology system.
| S-EPMC5301476 | biostudies-literature
Project description:ImportanceLow socioeconomic status is associated with higher all-cause mortality and risks for aging-related diseases. Biological aging is a potential process underlying health conditions related to social disadvantages, which may be present from birth onward.ObjectiveTo evaluate the association of parental socioeconomic status with telomere length (TL) at birth, a marker of biological aging.Design, setting, and participantsThis prospective birth cohort study was conducted among 1504 mother-newborn pairs in Belgium recruited between February 1, 2010, and July 1, 2017.ExposuresParental socioeconomic measures, including maternal educational level, occupation, paternal educational level, and neighborhood income based on median annual household income.Main outcomes and measuresMean relative TL was measured in cord blood and placental tissue. By constructing a principal component, an integrative socioeconomic measure was derived that integrates parental socioeconomic status and neighborhood income. Multivariable adjusted regression analyses were performed to associate the integrative socioeconomic measure and TL at birth.ResultsIn 1026 newborns (517 boys; mean [SD] gestational age, 39.2 [1.4] weeks), a higher socioeconomic status was associated with longer cord blood TL and placental TL. Each unit increment in the integrative socioeconomic status measure was associated with 2.1% (95% CI, 0.9%-3.4%; P < .001) longer cord blood TL in boys, while no association was observed for girls (0.5% longer cord blood TL; 95% CI, -0.9% to 1.8%; P = .50). The sex-specific socioeconomic status interaction revealed a stronger association in boys compared with newborn girls (1.6%; 95% CI, 0.02%-3.3%; P = .047 for interaction). In placental tissue, higher socioeconomic status was associated with 1.8% (95% CI, 0.3%-3.3%; P = .02) longer TL in newborn boys but not in girls (0.4% longer TL; 95% CI, -1.2% to 2.0%; P = .63). For placental tissue, no sex and socioeconomic status interaction on TL was observed (1.4%; 95% CI, -0.5% to 3.4%; P = .16 for interaction).Conclusions and relevanceThis study suggests that parental socioeconomic status is associated with newborn TL, especially in boys. The results indicate that familial social economic factors are associated with the potential cellular longevity of the next generation, with a potential higher transgenerational vulnerability for newborn boys.
| S-EPMC7199116 | biostudies-literature
Project description:AimThis nested case-control study sought to determine whether an accelerated rate of leukocyte telomere length (LTL) shortening over 6 years was associated with chronic periodontitis.Materials and methodsWe sampled cases (n = 178) with severe chronic periodontitis and controls (n = 178) with no/mild chronic periodontitis from the Atherosclerosis Risk in Communities study. Controls were frequency-matched to cases by study site, age, sex and race. Age ranged from 53 to 73 years. Severe chronic periodontitis was defined using the CDC-AAP case classification. LTL was measured from DNA collected at two time points, 6 years apart, with quantitative polymerase chain reaction relative to a single-copy control gene. Multiple linear regression evaluated associations between LTL measured at baseline, follow-up and change scores with severe chronic periodontitis, adjusting for potential confounders.ResultsCases had shorter LTL than controls at baseline (p = 0.03) and follow-up (p = 0.04) after adjusting for confounding. Overall there was a net reduction in LTL over time (p = 0.02). The rate of LTL did not differ between cases and controls (p = 0.80).ConclusionsLeukocyte telomere length shortening occurred at the same rate among adults with and without severe chronic periodontitis. This suggests that LTL shortening may have occurred earlier in the life course.
| S-EPMC4444215 | biostudies-literature
Project description:BackgroundAccelerated telomere shortening may cause cancer via chromosomal instability, making it a potentially useful biomarker. However, publications on blood telomere length (BTL) and cancer are inconsistent. We prospectively examined BTL measures over time and cancer incidence.MethodsWe included 792 Normative Aging Study participants with 1-4 BTL measurements from 1999 to 2012. We used linear mixed-effects models to examine BTL attrition by cancer status (relative to increasing age and decreasing years pre-diagnosis), Cox models for time-dependent associations, and logistic regression for cancer incidence stratified by years between BTL measurement and diagnosis.FindingsAge-related BTL attrition was faster in cancer cases pre-diagnosis than in cancer-free participants (pdifference = 0.017); all participants had similar age-adjusted BTL 8-14 years pre-diagnosis, followed by decelerated attrition in cancer cases resulting in longer BTL three (p = 0.003) and four (p = 0.012) years pre-diagnosis. Longer time-dependent BTL was associated with prostate cancer (HR = 1.79, p = 0.03), and longer BTL measured ≤ 4 years pre-diagnosis with any (OR = 3.27, p < 0.001) and prostate cancers (OR = 6.87, p < 0.001).InterpretationAge-related BTL attrition was faster in cancer cases but their age-adjusted BTL attrition began decelerating as diagnosis approached. This may explain prior inconsistencies and help develop BTL as a cancer detection biomarker.
| S-EPMC4535161 | biostudies-literature