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BACKGROUND: A recently developed urinary peptidomics biological aging clock can be used to study accelerated human aging. From 1990 to 2019, exposure to airborne particulate matter (PM) became the leading environmental risk factor worldwide. OBJECTIVES: This study investigated whether air pollution exposure is associated with accelerated urinary peptidomic aging, independent of calendar age, and whether this association is modified by other risk factors. METHODS: In a Flemish population, the urinary peptidomic profile (UPP) age (UPP-age) was derived from the urinary peptidomic profile measured by capillary electrophoresis coupled with mass spectrometry. UPP-age-R was calculated as the residual of the regression of UPP-age on chronological age, which reflects accelerated aging predicted by UPP-age, independent of chronological age. A high-resolution spatial-temporal interpolation method was used to assess each individual’s exposure to PM10, PM2.5, black carbon (BC), and nitrogen dioxide (NO2). Associations of UPP-age-R with these pollutants were investigated by mixed models, accounting for clustering by residential address and confounders. Effect modifiers of the associations between UPP-age-R and air pollutants that included 18 factors reflecting vascular function, renal function, insulin resistance, lipid metabolism, or inflammation were evaluated. Direct and indirect (via UPP-age-R) effects of air pollution on mortality were evaluated by multivariable adjusted Cox models. RESULTS: Among 660 participants (50.2% women; mean age: 50.7 y), higher exposure to PM10, PM2.5, BC, and NO2 was associated with a higher UPP-age-R. Studying effect modifiers showed that higher plasma levels of desphospho-uncarboxylated matrix Gla protein (dpucMGP), signifying poorer vitamin K status, steepened the slopes of UPP-age-R on the air pollutants. In further analyses among participants with dpucMGP =4.26 μg/L (median), an interquartile range (IQR) higher level in PM10, PM2.5, BC, and NO2 was associated with a higher UPP-age- R of 2.03 [95% confidence interval (CI): 0.60, 3.46], 2.22 (95% CI: 0.71, 3.74), 2.00 (95% CI: 0.56, 3.43), and 2.09 (95% CI: 0.77, 3.41) y, respectively. UPP-age-R was an indirect mediator of the associations of mortality with the air pollutants [multivariable-adjusted hazard ratios from 1.094 (95% CI: 1.000, 1.196) to 1.110 (95% CI: 1.007, 1.224)] in participants with a high dpucMGP, whereas no direct associations were observed. DISCUSSION: Ambient air pollution was associated with accelerated urinary peptidomics aging, and high vitamin K status showed a potential protective effect in this population. Current guidelines are insufficient to decrease the adverse health effects of airborne pollutants, including healthy aging trajectories. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence supports the concept of prenatal programming as an early factor in the aging process. DNA methylation age (DNAm age), global genome-wide DNA methylation (global methylation), telomere length (TL), and mitochondrial DNA content (mtDNA content) have independently been shown to be markers of aging, but their interrelationship and determinants at birth remain uncertain.Methods: We assessed the inter-correlation between the aging biomarkers DNAm age, global methylation, TL and mtDNA content using Pearson's correlation in 190 cord blood samples of the ENVIRONAGE birth cohort. TL and mtDNA content was measured via qPCR, while the DNA methylome was determined using the human 450K methylation Illumina microarray. Subsequently, DNAm age was calculated according to Horvath's epigenetic clock, and mean global, promoter, gene-body, and intergenic DNA methylation were determined. Path analysis, a form of structural equation modeling, was performed to disentangle the complex causal relationships among the aging biomarkers and their potential determinants.Results: DNAm age was inversely correlated with global methylation (r = -0.64, p < 0.001) and mtDNA content (r = - 0.16, p = 0.027). Cord blood TL was correlated with mtDNA content (r = 0.26, p < 0.001) but not with global methylation or DNAm age. Path analysis showed the strongest effect for global methylation on DNAm age with a decrease of 0.64 standard deviations (SD) in DNAm age for each SD (0.01%) increase in global methylation (p < 0.001). Among the applied covariates, newborn sex and season of delivery were the strongest determinants of aging biomarkers.Conclusions: We provide insight into molecular aging signatures at the start of life, including their interrelations and determinants, showing that cord blood DNAm age is inversely associated with global methylation and mtDNA content but not with newborn telomere length. Our findings demonstrate that cord blood TL and DNAm age relate to different pathways/mechanisms of biological aging and can be influenced by environmental factors already at the start of life. These findings are relevant for understanding fetal programming and for the early prevention of noncommunicable diseases. [ABSTRACT FROM AUTHOR]

Appetite hormones are considered a promising target in fighting obesity as impaired appetite hormone levels have already been associated with obesity. However, further insights in the drivers of appetite hormone levels are needed. In this study, we investigated the associations of fasting appetite hormone levels with lifestyle and environmental exposures in children and adolescents. A total of 534 fasting blood samples were collected from children and adolescents (4-16y,50% boys) and appetite hormone levels (glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide (PP), leptin and ghrelin) were measured. Exposures included dietary quality (fiber-rich food intake, sugar propensity, fat propensity), psychosocial stress (happiness, negative emotions, negative life events and emotional problems), sleep duration, physical activity and environmental quality (long term black carbon (BC), particulate matter <2.5 μM (PM 2.5), nitrogen dioxide (NO 2) exposure, and green space in a 100 m and 2000 m radius around the residence). A multi-exposure score was calculated to combine all the exposures at study in one measure. Associations of individual exposures and multi-exposure score with appetite hormone levels were evaluated using linear mixed regression models adjusting for sex, age, socioeconomic status, waist-to-height ratio and multiple testing. GLP-1 was associated with air pollution exposure (NO 2 β* = -0.13, BC β* = -0.15, PM 2.5 β* = -0.16, all p < 0.001). Leptin was associated with green space in a 100 m radius around the residence (β* = -0.11; p = 0.002). Ghrelin was associated with negative emotions (active ghrelin β* = -0.16; p = 0.04, total ghrelin β* = -0.23; p = 0.0051) and happiness (active ghrelin β* = 0.25; p < 0.001, total ghrelin β* = 0.26; p < 0.001). Furthermore, total ghrelin levels were associated with the multi-exposure score, reflecting unhealthy exposures and lifestyle (β* = -0.22; p = 0.036). Our findings provide new insights into the associations of exposures with appetite hormone levels, which are of high interest for preventive obesity research. Further research is crucial to reveal the underlying mechanisms of the observed associations. • Associations of 14 exposures with 5 appetite hormones were studied in children. • Air pollution is negatively associated with fasting glucagon-like-peptide 1 levels. • Residential green space is negatively associated with fasting leptin levels. • Happiness is positively associated with active and total ghrelin levels. • Negative emotions show negative associations with total ghrelin levels. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although studies have provided estimates of premature mortality to either heat or cold in adult populations, and fetal exposure to ambient temperature may be associated with life expectancy, the effects of temperature on aging in early life have not yet been studied. Telomere length (TL) is a marker of biological aging, and a short TL at birth may predict lifespan and disease susceptibility later in life. OBJECTIVES: We studied to what extent prenatal ambient temperature exposure is associated with newborn TL. METHODS: In the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort in Flanders, Belgium, we measured cord blood and placental TL in 1,103 mother-newborn pairs (singletons with ≥36 wk of gestation) using a quantitative real-time polymerase chain reaction (qPCR) method. We associated newborn TL with average weekly exposure to ambient temperature using distributed lag nonlinear models (DLNMs) while controlling for potential confounders. Double-threshold DLNMs were used to estimate cold and heat thresholds and the linear associations between temperature and TL below the cold threshold and above the heat threshold. RESULTS: Prenatal temperature exposure above the heat threshold (19.5°C) was associated with shorter cord blood TL. The association with a 1°C increase in temperature was strongest at week 36 of gestation and resulted in a 3.29% [95% confidence interval (CI): -4.67, -1.88] shorter cord blood TL. Consistently, prenatal temperature exposure below the cold threshold (5.0°C) was associated with longer cord blood TL. The association with a 1°C decrease in temperature was strongest at week 10 of gestation with 0.72% (95% CI: 0.46, 0.97) longer cord blood TL. DISCUSSION: Our study supports potential effects of prenatal temperature exposure on longevity and disease susceptibility later in life. Future climate scenarios might jeopardize the potential molecular longevity of future generations from birth onward. [ABSTRACT FROM AUTHOR]

Highlights • Telomere lengths are cellular memories of exposures to inflammation and oxidative stress. • Residential green space, low traffic exposure, and long-term lower exposure to particulate air pollution are associated with longer telomeres. • Adverse environmental exposures may have a long lasting molecular footprint on the ageing process, as reflected by shorter telomere length. • Shorter telomeres reflect higher disease susceptibility and a potential shorter life expectancy. • Adequate reductions in, and protections against, pollutants may lead to decreased comorbidities and increased life-expectancy. Abstract Studies suggest that leukocyte telomere length is an index of systemic ageing. Here, we discuss telomere length as a marker of biological ageing in relation to residential landscape (greenness), residential air pollution and work-related exposures. Telomere lengths are memories of cumulative oxidative and inflammatory stress, and show to have inverse associations with the risk of non-communicable diseases. For this reason, telomeres are considered as markers of biological ageing. Studies at birth, in children, young adulthood, and elderly show that residential green space, lower traffic exposure and long-term lower exposure to particulate air pollution are associated with longer telomeres. Work-related exposures including exposure to toxic metals, polycyclic aromatic hydrocarbons and particulate matter are associated with shorter telomeres for a given age. In contrast to chronic exposures, evidence is present of the observation that recent exposure is associated with longer telomeres. Our overview shows that the magnitude of residential and work-related environmental factors on telomere length are often as important as many classical lifestyle factors. [ABSTRACT FROM AUTHOR]

Beyond prostaglandins, the function of eicosanoids and other oxylipins in pregnancy and labor is poorly understood. In contrast to earlier work focusing on preterm infants, we investigated how oxylipin levels in newborns (measured in cord blood) vary during the last weeks of pregnancy in 190 mother-newborns (≥37 weeks of gestation) of the ENVIR ON AGE birth cohort, Belgium. We found increased levels of PGE 2 ( p = 0.003), PGF 2α (p = 0.042), 8,9-DHET ( p = 0.037), 11-HETE ( p = 0.034), and 15-HETrE ( p = 0.008) associated with full term pregnancy compared to early term labor. Furthermore, late vs early term was associated with increased levels of PGE 2 ( p = 0.012) and TXB 2 ( p = 0.033), while late vs full term was associated with decreased levels of 14,15-DHET ( p = 0.029), 11,12-DHET ( p = 0.033), and 5-HETE ( p = 0.045). To summarize, nine eicosanoids, derived via three enzymatic pathways, were significantly associated with gestational age. Eight of these were derived from arachidonic acid, and one from dihomo-γ-linolenic acid. [ABSTRACT FROM AUTHOR]

BACKGROUND: As part of the lipidome, oxylipins are bioactive lipid compounds originating from oxidation of different fatty acids. Oxylipins could provide a new target in the developmental origins model or the ability of early life exposure to change biology. Objectives: We studied the association between in utero PM[sup 2.5] (particulate matter with aerodynamic diameter < 2.5 μm) exposure and oxylipin profiles in newborns. Methods: Thirty-seven oxylipins reflecting the cyclooxygenase (COX), lipoxygenase (5-LOX and 12/15-LOX), and cytochrome P450 (CYP) pathways were assayed in 197 cord blood plasma samples from the ENVIR ON AGE birth cohort. Principal component (PC) analysis and multiple regression models were used to estimate associations of in utero PM[sup 2.5] exposure with oxylipin pathways and individual metabolites. Results: A principal component representing the 5-LOX pathway (6 metabolites) was significantly positively associated with PM[sup 2.5] exposure during the entire (multiple testing-adjusted q-value = 0.05) and second trimester of pregnancy (q = 0.05). A principal component representing the 12/15-LOX pathway (11 metabolites) was positively associated with PM[sup 2.5] exposure during the second trimester of pregnancy (q = 0.05). PM[sup 2.5] was not significantly associated with the COX pathway during any time period. There was a positive but nonsignificant association between second-trimester PM[sup 2.5] and the CYP pathway (q = 0.16). Conclusion: In utero exposure to particulate matter, particularly during the second trimester, was associated with differences in the cord blood levels of metabolites derived from the lipoxygenase pathways. These differences may indicate an effect of air pollution during in utero life on the inflammatory state of the newborn at birth. Oxylipins may be important mediators between early life exposures and health outcomes later in life. CITATION: Martens DS, Gouveia S, Madhloum N, Janssen BG, Plusquin M, Vanpoucke C, Lefebvre W, Forsberg B, Nording M, Nawrot TS. 2017. Neonatal cord blood oxylipins and exposure to particulate matter in the early-life environment: an ENVIRONAGE birth cohort study. Environ Health Perspect 125:691-698; http://dx.doi.org/10.1289/EHP291 [ABSTRACT FROM AUTHOR]

Background: Newborn telomere length sets telomere length for later life. At birth, telomere length is highly variable among newborns and the environmental factors during in utero life for this observation remain largely unidentified. Obesity during pregnancy might reflect an adverse nutritional status affecting pregnancy and offspring outcomes, but the association of maternal pre-pregnancy body mass index (BMI) with newborn telomere length, as a mechanism of maternal obesity, on the next generation has not been addressed. Methods: Average relative telomere lengths were measured in cord blood (n = 743) and placental tissue (n = 702) samples using a quantitative real-time PCR method from newborns from the ENVIRONAGE birth cohort in Belgium. By using univariate and multivariable adjusted linear regression models we addressed the associations between pre-pregnancy BMI and cord blood and placental telomere lengths. Results: Maternal age was 29.1 years (range, 17-44) and mean (SD) pre-pregnancy BMI was 24.1 (4.1) kg/m². Decline in newborn telomere length occurred in parallel with higher maternal pre-pregnancy BMI. Independent of maternal and paternal age at birth, maternal education, gestational age, newborn gender, ethnicity, birthweight, maternal smoking status, parity, cesarean section, and pregnancy complications, each kg/m² increase in pre-pregnancy BMI was associated with a -0.50 % (95 % CI, -0.83 to -0.17 %; P = 0.003) shorter cord blood telomere length and a -0.66 % (95 % CI, -1.06 to -0.25 %; P = 0.002) shorter placental telomere length. Conclusions: Maternal pre-pregnancy BMI is associated with shorter newborn telomere lengths as reflected by cord blood and placental telomeres. These findings support the benefits of a pre-pregnancy healthy weight for promoting molecular longevity from early life onwards. [ABSTRACT FROM AUTHOR]

Telomeres are vulnerable to various environmental exposures and lifestyle factors, encompassed in the exposome. Recent research shows that telomere length is substantially determined early in life and that exposures in childhood may have important consequences in setting later life telomere length. We explore in a child population the associations of 17 exposures with telomere length and longitudinal telomere change. Children (2.8–10.3y at baseline, 51.3% boys) were followed-up for five to seven years. Relative telomere length was measured at baseline and follow-up using quantitative real-time PCR. Exposures and lifestyle factors included: body composition (body mass index and waist circumference), dietary habits (sugar- and fat-rich food intake, vegetables and fruit intake), psychosocial stress (events, emotions, behaviour), sleep duration, physical activity, and residential environmental quality (longterm black carbon, particulate matter exposure, and residential green space). Cross-sectional (n=182) and longitudinal (n=150) analyses were assessed using linear regression models, adjusting for age, sex, socioeconomic status and multiple testing. Our longitudinal analyses showed that higher residential green space at baseline was associated with (β=0.261, p=0.002) lower telomere attrition and that children with a higher waist circumference at baseline showed a higher telomere attrition (β=−0.287, p=0.001). These two predictors were confirmed via LASSO variable selection and correction for multiple testing. In addition, children with more unhealthy exposures at baseline had a significantly higher telomere attrition over the follow-up period compared to children with more healthy exposures (β=−0.200, p=0.017). Waist circumference and residential green space were identified as predictors associated with telomere attrition in childhood. These results further support the advantages of a healthy lifestyle from early age onwards and the importance of a green environment to promote molecular longevity from childhood onwards. • Telomere attrition over 5-7y and 17 exposures were measured in 4-7y old children. • More unhealthy exposures at baseline resulted in higher telomere attrition. • Residential green space at baseline was associated with lower telomere attrition. • Waist circumference partially mediated this association. • Lifestyle and green space during childhood seems important for molecular longevity. [ABSTRACT FROM AUTHOR]

High blood pressure (BP) and type‐2 diabetes (T2DM) are forerunners of chronic kidney disease and left ventricular dysfunction. Home BP telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling risk stratification and personalized prevention. UPRIGHT‐HTM (NCT04299529) is an investigator‐initiated, multicenter, open‐label, randomized trial with blinded endpoint evaluation designed to assess the efficacy of HTM plus UPP (experimental group) over HTM alone (control group) in guiding treatment in asymptomatic patients, aged 55–75 years, with ≥5 cardiovascular risk factors. From screening onwards, HTM data can be freely accessed by all patients and their caregivers; UPP results are communicated early during follow‐up to patients and caregivers in the intervention group, but at trial closure in the control group. From May 2021 until January 2023, 235 patients were screened, of whom 53 were still progressing through the run‐in period and 144 were randomized. Both groups had similar characteristics, including average age (62.0 years) and the proportions of African Blacks (81.9%), White Europeans (16.7%), women 56.2%, home (31.2%), and office (50.0%) hypertension, T2DM (36.4%), micro‐albuminuria (29.4%), and ECG (9.7%) and echocardiographic (11.5%) left ventricular hypertrophy. Home and office BP were 128.8/79.2 mm Hg and 137.1/82.7 mm Hg, respectively, resulting in a prevalence of white‐coat, masked and sustained hypertension of 40.3%, 11.1%, and 25.7%. HTM persisted after randomization (48 681 readings up to 15 January 2023). In conclusion, results predominantly from low‐resource sub‐Saharan centers proved the feasibility of this multi‐ethnic trial. The COVID‐19 pandemic caused delays and differential recruitment rates across centers. [ABSTRACT FROM AUTHOR]

With urinary proteomics profiling (UPP) as exemplary omics technology, this review describes a workflow for the analysis of omics data in large study populations. The proposed workflow includes: (i) planning omics studies and sample size considerations; (ii) preparing the data for analysis; (iii) preprocessing the UPP data; (iv) the basic statistical steps required for data curation; (v) the selection of covariables; (vi) relating continuously distributed or categorical outcomes to a series of single markers (e.g., sequenced urinary peptide fragments identifying the parental proteins); (vii) showing the added diagnostic or prognostic value of the UPP markers over and beyond classical risk factors, and (viii) pathway analysis to identify targets for personalized intervention in disease prevention or treatment. Additionally, two short sections respectively address multiomics studies and machine learning. In conclusion, the analysis of adverse health outcomes in relation to omics biomarkers rests on the same statistical principle as any other data collected in large population or patient cohorts. The large number of biomarkers, which have to be considered simultaneously requires planning ahead how the study database will be structured and curated, imported in statistical software packages, analysis results will be triaged for clinical relevance, and presented. [ABSTRACT FROM AUTHOR]

Telomere length is associated with longevity and survival in multiple species. In human population-based studies, multiple prenatal factors have been described to be associated with a newborn's telomere length. In the present study, we measured relative leukocyte telomere length in 210 Holstein Friesian heifers, within the first ten days of life. The dam's age, parity, and milk production parameters, as well as environmental factors during gestation were assessed for their potential effect on telomere length. We found that for both primi- and multiparous dams, the telomere length was 1.16% shorter for each day increase in the calf's age at sampling (P = 0.017). The dam's age at parturition (P = 0.045), and the median temperature-humidity index (THI) during the third trimester of gestation (P = 0.006) were also negatively associated with the calves' TL. Investigating multiparous dams separately, only the calf's age at sampling was significantly and negatively associated with the calves' TL (P = 0.025). Results of the present study support the hypothesis that in cattle, early life telomere length is influenced by prenatal factors. Furthermore, the results suggest that selecting heifers born in winter out of young dams might contribute to increased longevity in dairy cattle. [ABSTRACT FROM AUTHOR]

Background: Studies often evaluate mental health and well-being in association with individual health behaviours although evaluating multiple health behaviours that co-occur in real life may reveal important insights into the overall association. Also, the underlying pathways of how lifestyle might affect our health are still under debate. Here, we studied the mediation of different health behaviours or lifestyle factors on mental health and its effect on core markers of ageing: telomere length (TL) and mitochondrial DNA content (mtDNAc).Methods: In this study, 6054 adults from the 2018 Belgian Health Interview Survey (BHIS) were included. Mental health and well-being outcomes included psychological and severe psychological distress, vitality, life satisfaction, self-perceived health, depressive and generalised anxiety disorder and suicidal ideation. A lifestyle score integrating diet, physical activity, smoking status, alcohol consumption and BMI was created and validated. On a subset of 739 participants, leucocyte TL and mtDNAc were assessed using qPCR. Generalised linear mixed models were used while adjusting for a priori chosen covariates.Results: The average age (SD) of the study population was 49.9 (17.5) years, and 48.8% were men. A one-point increment in the lifestyle score was associated with lower odds (ranging from 0.56 to 0.74) for all studied mental health outcomes and with a 1.74% (95% CI: 0.11, 3.40%) longer TL and 4.07% (95% CI: 2.01, 6.17%) higher mtDNAc. Psychological distress and suicidal ideation were associated with a lower mtDNAc of - 4.62% (95% CI: - 8.85, - 0.20%) and - 7.83% (95% CI: - 14.77, - 0.34%), respectively. No associations were found between mental health and TL.Conclusions: In this large-scale study, we showed the positive association between a healthy lifestyle and both biological ageing and different dimensions of mental health and well-being. We also indicated that living a healthy lifestyle contributes to more favourable biological ageing. [ABSTRACT FROM AUTHOR]

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 NO 2 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 NO 2 and BTEX exposure levels were determined via compact passive diffusion samplers carried on the person prior to baseline (NO 2 : 14.2 (9.4–17.2) μg/m³; Benzene: 3.1 (2.1–5.3) μg/m³) and 6-month follow-up (NO 2 : 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 NO 2 (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 NO 2 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 NO 2 and benzene are associated with molecular ageing as indicated by LTL in healthy women residing in the Cape Town region. Image 1 • First ever report on the effects of personal NO 2 and benzene exposure on LTL in a South African population. • Personal NO 2 and benzene exposure was inversely associated with leukocyte telomere length. • The magnitude of the effects corresponds to >6-year increase in chronological age. [ABSTRACT FROM AUTHOR]

Background: In the early-life environment, proper development of the placenta is essential for both fetal and maternal health. Telomere length at birth has been related to life expectancy. MicroRNAs (miRNAs) as potential epigenetic determinants of telomere length at birth have not been identified. In this study, we investigate whether placental miRNA expression is associated with placental telomere length at birth.Methods: We measured the expression of seven candidate miRNAs (miR-16-5p, -20a-5p, -21-5p, -34a-5p, 146a-5p, -210-3p and -222-3p) in placental tissue at birth in 203 mother-newborn (51.7% girls) pairs from the ENVIRONAGE birth cohort. We selected miRNAs known to be involved in crucial cellular processes such as inflammation, oxidative stress, cellular senescence related to aging. Placental miRNA expression and relative average placental telomere length were measured using RT-qPCR.Results: Both before and after adjustment for potential covariates including newborn's ethnicity, gestational age, paternal age, maternal smoking status, maternal educational status, parity, date of delivery and outdoor temperature during the 3rd trimester of pregnancy, placental miR-34a, miR-146a, miR-210 and miR-222 expression were significantly (p ≤ 0.03) and positively associated with placental relative telomere length in newborn girls. In newborn boys, only higher expression of placental miR-21 was weakly (p = 0.08) associated with shorter placental telomere length. Significant miRNAs explain around 6-8% of the telomere length variance at birth.Conclusions: Placental miR-21, miR-34a, miR-146a, miR-210 and miR-222 exhibit sex-specific associations with telomere length in placenta. Our results indicate miRNA expression in placental tissue could be an important determinant in the process of aging starting from early life onwards. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis is a fatal lung disease characterized by a progressive formation of fibroblastic foci in the interstitium. This disease is strongly associated with telomere dysfunction but the extent of telomere shortening and consequent chromosomal damage within IPF lungs and with regional disease severity remains unknown.Methods: Explanted IPF lungs (n = 10) were collected from transplant surgeries with six samples per lung analysed to capture the regional heterogeneity ranging from mild to severe disease. Non-used donor lungs (n = 6) were collected as "healthy" controls. Structural changes related to disease severity (microCT surface density), relative telomere length (real-time qPCR), and quantitative histology of chromosomal damage (γ-H2A.X) and extracellular matrix (elastin, total collagen, collagen 1, and collagen 3) were measured. A multivariate linear mixed-effects model controlling for subject was used to identify association of disease severity or fibrotic markers with telomere length and chromosomal damage.Results: We observed shorter telomere length (p = 0.001) and increased chromosomal damage (p = 0.018) in IPF lungs compared to controls. In IPF lungs, telomere length was associated with total collagen (p < 0.001) but not with structural changes of disease severity. Chromosomal damage was positively associated with increased elastin (p = 0.006) and negatively with structural disease severity (p = 0.046). Extensive γ-H2A.X staining was also present in airway epithelial cells.Conclusions: Telomere length and chromosomal damage are involved in IPF with regional variation in telomere length and chromosomal damage associated with pathological changes in tissue structure and the extracellular matrix. [ABSTRACT FROM AUTHOR]

BACKGROUND: Telomere length is a molecular marker of biological aging. OBJECTIVE: Here we investigated whether early-life exposure to residential air pollution was associated with leukocyte telomere length (LTL) at 8 y of age. METHODS: In a multicenter European birth cohort study, HELIX (Human Early Life Exposome) (n=1,396), we estimated prenatal and 1-y childhood exposure to nitrogen dioxide (NO2), particulate matter with aerodynamic diameter ≤2:5 lm (PM2:5), and proximity to major roads. Average relative LTL was measured using quantitative real-time polymerase chain reaction (qPCR). Effect estimates of the association between LTL and prenatal, 1-y childhood air pollution, and proximity to major roads were calculated using multiple linear mixed models with a random cohort effect and adjusted for relevant covariates. RESULTS: LTL was inversely associated with prenatal and 1-y childhood NO2 and PM2:5 exposures levels. Each standard deviation (SD) increase in prenatal NO2 was associated with a −1:5% (95% CI: −2:8, −0:2) change in LTL. Prenatal PM2:5 was nonsignificantly associated with LTL (−0:7% per SD increase; 95% CI: −2:0, 0.6). For each SD increment in 1-y childhood NO2 and PM2:5 exposure, LTL shortened by −1:6% (95% CI: −2:9, −0:4) and −1:4% (95% CI: −2:9, 0.1), respectively. Each doubling in residential distance to nearest major road during childhood was associated with a 1.6% (95% CI: 0.02, 3.1) lengthening in LTL. CONCLUSION: Lower exposures to air pollution during pregnancy and childhood were associated with longer telomeres in European children at 8 y of age. These results suggest that reductions in traffic-related air pollution may promote molecular longevity, as exemplified by telomere length, from early life onward. [ABSTRACT FROM AUTHOR]

Exposure to various forms of stress has been associated with shorter telomere length (TL). However, the molecular underpinnings of this effect are poorly understood. Based on an understanding of the key role of the reverse transcriptase enzyme telomerase in regulating TL, and building upon our previous work in developing and validating a biomarker of the capacity of cells to express telomerase (maximal telomerase activity capacity (mTAC)), we examine here the hypotheses that mTAC is positively associated with TL and that the effect of stress on TL is mediated by individual differences in mTAC. In a proof-of-principle study of 28 healthy women and men we quantified the cortisol response to a standardized stress challenge, the Trier Social Stress Test (TSST), and we concurrently assessed peripheral blood mononuclear cell (PBMC) mTAC and TL. Our results indicated that higher mTAC levels were associated with longer TL (r = 0.50, p =.01). Moreover, mediational analysis suggested that the effect of the cortisol stress response on TL was mediated by mTAC (completely standardized β = −0.17, bootstrap CI95 %: −0.44 to −0.01). Thus, our findings support the premise that individual differences in the capacity of cells to up-regulate telomerase may represent a key mediator in the link between stress and TL. • Individuals with a higher physiological stress response show shorter telomere length (TL). • Maximal telomerase activity capacity (mTAC) is related to shorter telomeres. • mTAC mediates the relationship between the physiological stress response and TL. [ABSTRACT FROM AUTHOR]

Background: While biological age in adults is often understood as representing general health and resilience, the conceptual interpretation of accelerated biological age in children and its relationship to development remains unclear. We aimed to clarify the relationship of accelerated biological age, assessed through two established biological age indicators, telomere length and DNA methylation age, and two novel candidate biological age indicators, to child developmental outcomes, including growth and adiposity, cognition, behavior, lung function and the onset of puberty, among European school-age children participating in the HELIX exposome cohort. Methods: The study population included up to 1173 children, aged between 5 and 12 years, from study centres in the UK, France, Spain, Norway, Lithuania, and Greece. Telomere length was measured through qPCR, blood DNA methylation, and gene expression was measured using microarray, and proteins and metabolites were measured by a range of targeted assays. DNA methylation age was assessed using Horvath's skin and blood clock, while novel blood transcriptome and 'immunometabolic' (based on plasma proteins and urinary and serum metabolites) clocks were derived and tested in a subset of children assessed six months after the main follow-up visit. Associations between biological age indicators with child developmental measures as well as health risk factors were estimated using linear regression, adjusted for chronological age, sex, ethnicity, and study centre. The clock derived markers were expressed as Δ age (i.e. predicted minus chronological age). Results: Transcriptome and immunometabolic clocks predicted chronological age well in the test set (r=0.93 and r=0.84 respectively). Generally, weak correlations were observed, after adjustment for chronological age, between the biological age indicators. Among associations with health risk factors, higher birthweight was associated with greater immunometabolic Δ age, smoke exposure with greater DNA methylation Δ age, and high family affluence with longer telomere length. Among associations with child developmental measures, all biological age markers were associated with greater BMI and fat mass, and all markers except telomere length were associated with greater height, at least at nominal significance (p<0.05). Immunometabolic Δ age was associated with better working memory (p=4 e-3) and reduced inattentiveness (p=4 e-4), while DNA methylation Δ age was associated with greater inattentiveness (p=0.03) and poorer externalizing behaviors (p=0.01). Shorter telomere length was also associated with poorer externalizing behaviors (p=0.03). Conclusions: In children, as in adults, biological aging appears to be a multi-faceted process and adiposity is an important correlate of accelerated biological aging. Patterns of associations suggested that accelerated immunometabolic age may be beneficial for some aspects of child development while accelerated DNA methylation age and telomere attrition may reflect early detrimental aspects of biological aging, apparent even in children. Funding: UK Research and Innovation (MR/S03532X/1); European Commission (grant agreement numbers: 308333; 874583). [ABSTRACT FROM AUTHOR]

Introduction Cardio-metabolic risk factors including insulin levels are at young age barely perceived as harmful, but over time these risk factors may track and lead to higher risk of metabolic syndrome. Studies showed that exposure to air pollution is associated with an increased risk of insulin resistance in childhood. We determined whether the origin of type 2 diabetes can be found in the early childhood by examining the levels of insulin in the neonatal cord blood and whether this can be considered as a disease marker for later life. Methods In the ENVIR ON AGE (ENVIRonmental influence ON early AGEing) birth cohort, we recruited 620 mother-infant pairs between February 2nd 2010 until August 12th 2014 at the East-Limburg Hospital in Genk, Belgium. We investigated in 590 newborns the association between cord plasma insulin levels and exposure to particulate matter (PM 2.5 and PM 10 ) and nitrogen dioxide (NO 2 ) in various exposure windows during pregnancy. Trimester-specific air pollutant exposure levels were estimated for each mother's home address using a spatiotemporal model. Results Cord plasma insulin levels averaged 33.1 pmol/L (25-75th percentile: 20.1-53.5), while PM 2.5 exposure during pregnancy averaged (SD) 13.7 μg/m 3 (2.4). Independent of maternal age, newborn's sex, birth weight, gestational age, parity, early-pregnancy BMI, ethnicity, smoking status, time of the day, maternal education, time of delivery, and season of delivery, cord plasma insulin levels increased with 15.8% (95% CI 7.8 to 24.4, p < 0.0001) for each SD increment in PM 2.5 levels during the entire pregnancy and was most pronounced in the 2nd trimester (13.1%, 95% CI 3.4 to 23.7, p = 0.007) of pregnancy. The results for PM 10 exposure were similar with those of PM 2.5 exposure but we did not observe an association between cord blood insulin levels and NO 2 exposure. Conclusions Exposure to particulate air pollution during pregnancy is associated with increased levels of cord plasma insulin at birth. The public health relevance of this association is demonstrated by the fact that a 2.4 μg/m 3 (SD) increase in PM 2.5 during pregnancy on cord plasma insulin levels corresponds to the effect-size of a 9 kg/m 2 higher early-pregnancy BMI on cord plasma. Particulate air pollution induced changes in cord plasma insulin levels during early life and might be a risk factor in the development of metabolic disease, such as glucose intolerance or type 2 diabetes, later in life. [ABSTRACT FROM AUTHOR]

Background: Mitochondria play an important role in the energy metabolism and are susceptible to environmental pollution. Prenatal air pollution exposure has been linked with childhood obesity. Placental mtDNA mutations have been associated with prenatal particulate matter exposure and MT-ND4L10550A>G heteroplasmy has been associated with BMI in adults. Therefore, we hypothesized that in utero PM2.5 exposure is associated with cord blood MT-ND4L10550A>G heteroplasmy and early life growth. In addition, the role of cord blood MT-ND4L10550A>G heteroplasmy in overweight during early childhood is investigated.Methods: This study included 386 mother-newborn pairs. Outdoor PM2.5 concentrations were determined at the maternal residential address. Cord blood MT-ND4L10550A>G heteroplasmy was determined using Droplet Digital PCR. Associations were explored using logistic regression models and distributed lag linear models. Mediation analysis was performed to quantify the effects of prenatal PM2.5 exposure on childhood overweight mediated by cord blood MT-ND4L10550A>G heteroplasmy.Results: Prenatal PM2.5 exposure was positively associated with childhood overweight during the whole pregnancy (OR = 2.33; 95% CI: 1.20 to 4.51; p = 0.01), which was mainly driven by the second trimester. In addition, prenatal PM2.5 exposure was associated with cord blood MT-ND4L10550A>G heteroplasmy from gestational week 9 - 13. The largest effect was observed in week 10, where a 5 µg/m3 increment in PM2.5 was linked with cord blood MT-ND4L10550A>G heteroplasmy (OR = 0.93; 95% CI: 0.87 to 0.99). Cord blood MT-ND4L10550A>G heteroplasmy was also linked with childhood overweight (OR = 3.04; 95% CI: 1.15 to 7.50; p = 0.02). The effect of prenatal PM2.5 exposure on childhood overweight was mainly direct (total effect OR = 1.18; 95% CI: 0.99 to 1.36; natural direct effect OR = 1.20; 95% CI: 1.01 to 1.36)) and was not mediated by cord blood MT-ND4L10550A>G heteroplasmy.Conclusions: Cord blood MT-ND4L10550A>G heteroplasmy was linked with childhood overweight. In addition, in utero exposure to PM2.5 during the first trimester of pregnancy was associated with cord blood MT-ND4L10550A>G heteroplasmy in newborns. Our analysis did not reveal any mediation of cord blood MT-ND4L10550A>G heteroplasmy in the association between PM2.5 exposure and childhood overweight. [ABSTRACT FROM AUTHOR]

Telomere length (TL) and mitochondrial DNA (mtDNA) are central markers of vital biological mechanisms, including cellular aging. Prenatal air pollution exposure may impact molecular markers of aging leading to adverse health effects. To perform a systematic review on human population-based studies investigating the association between prenatal air pollution exposure and TL or mtDNA content at birth. Searches were undertaken on PubMed and Web of Science until July 2023. The framework of the review was based on the PRISMA-P guidelines. Nineteen studies studied prenatal air pollution and TL or mtDNA content at birth. Studies investigating TL or mtDNA content measured at any other time or did not evaluate prenatal air pollution were excluded. Twelve studies (including 4381 participants with study sample range: 97 to 743 participants) investigated newborn TL and eight studies (including 3081 participants with study sample range: 120 to 743 participants) investigated mtDNA content at birth. Seven studies focused on particulate matter (PM 2.5) exposure and newborn TL of which all, except two, showed an inverse association in at least one of the gestational trimesters. Of the eight studies on mtDNA content, four focused on PM 2.5 air pollution with two of them reporting an inverse association. For PM 2.5 exposure, observations on trimester-specific effects were inconsistent. Current literature showing associations with other prenatal air pollutants (including nitrogen oxides, sulfur dioxide, carbon monoxide and ozone) is inconsistent. This review provides initial evidence that prenatal PM 2.5 exposure impacts the telomere-mitochondrial axis of aging at birth. The current evidence did not reveal harmonious observations for trimester-specific associations nor showed consistent effects of other air pollutants. Future studies should elucidate the specific contribution of prenatal exposure to pollutants other than PM in relation to TL and mtDNA content at birth, and the potential later life health consequences. [ABSTRACT FROM AUTHOR]

Studies based on self-reported alcohol consumption and telomere length show inconsistent results. Therefore, we studied the association between gamma-glutamyl transferase (GGT), a widely used biomarker of alcohol intake, and telomere length. The possible health relevance in young adulthood was explored by investigating cardiometabolic risk factors. Mixed modelling was performed to examine GGT and alcohol consumption in association with telomere length in buccal cells of 211 adults between 18 and 30 years old of the East Flanders Prospective Twin Survey. In addition, we investigated the association between GGT and cardiometabolic risk factors; waist circumference, systolic blood pressure, fasting glucose, HDL cholesterol, and triglycerides. Although we did not observe an association between self-reported alcohol consumption and telomere length, our results show that a doubling in serum GGT is associated with 7.80% (95% CI − 13.9 to − 1.2%; p = 0.02) shorter buccal telomeres, independently from sex, chronological age, educational level, zygosity and chorionicity, waist-to-hip ratio and smoking. The association between GGT was significant for all five cardiometabolic risk factors, while adjusting for age. We show that GGT, a widely used biomarker of alcohol consumption, is associated with telomere length and with risk factors of cardiometabolic syndrome, despite the young age of this study population. [ABSTRACT FROM AUTHOR]

Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5–71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by − 0.85% (− 0.19 to − 0.52) (p ≤ 0.0001) and − 14% (− 28.22 to − 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05–1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome. [ABSTRACT FROM AUTHOR]

Shortened telomere length (TL) has been associated with lower cognitive performance, different neurological diseases in adults, and certain neurodevelopmental disorders in children. However, the evidence about the association between TL and neuropsychological developmental outcomes in children from the general population is scarce. Therefore, this study aimed to explore the association between TL and neuropsychological function in children 4–5 years of age. We included 686 children from the INMA Project, a population-based birth cohort in Spain. Leucocyte TL was determined by quantitative PCR method, and neuropsychological outcomes were measured using the McCarthy Scales of Children’s Abilities (MCSA). Multiple linear regression models were used to estimate associations adjusted for potential confounding variables. Main findings showed that a longer TL was associated with a higher mean working memory score (β = 4.55; 95% CI = 0.39, 8.71). In addition, longer TL was associated with a higher mean global quantitative score (β = 3.85; 95% CI = −0.19, 7.89), although the association was marginally significant. To our knowledge, this is the first study that shows a positive association between TL and better neuropsychological outcomes in children. Although further research is required to confirm these results, this study supports the hypothesis that TL is essential in protecting and maintaining a child’s health, including cognitive functions such as working memory. [ABSTRACT FROM AUTHOR]

• First study to report changes in TL and mtDNAcn, in MWCNT exposed workers. • MWCNT-exposure was associated with 18.30 % increase in blood TL (95 % CI: 7.15–30.62 %; p = 0.001). • MWCNT-exposure is associated with 35.21 % increase in mtDNAcn (95 % CI: 19.12–53.46 %). • Increase may have implication in disease development. • No association regarding possible disease outcome can be made at the moment. Carbon nanotubes (CNTs) except MWCNT-7 have been classified as Group 3 [" Not classifiable as to its carcinogenicity to humans "] by the IARC. Despite considerable mechanistic evidence in vitro / in vivo , the classification highlights a general lack of data, especially among humans. In our previous study, we reported epigenetic changes in the MWCNT exposed workers. Here, we evaluated whether MWCNT can also cause alterations in aging related features including relative telomere length (TL) and/or mitochondrial copy number (mtDNAcn). Relative TL and mtDNAcn were measured on extracted DNA from peripheral blood from MWCNT exposed workers (N = 24) and non-exposed controls (N = 43) using a qPCR method. A higher mtDNAcn and longer TL were observed in MWCNT exposed workers when compared to controls. Independent of age, sex, smoking behavior, alcohol consumption and BMI, MWCNT-exposure was associated with an 18.30 % increase in blood TL (95 % CI: 7.15–30.62 %; p = 0.001) and 35.21 % increase in mtDNAcn (95 % CI: 19.12–53.46 %). Our results suggest that exposure to MWCNT can induce an increase in the mtDNAcn and TL; however, the mechanistic basis or consequence of such change requires further experimental studies. [ABSTRACT FROM AUTHOR]

Background: Telomere shortening has been associated with several lung diseases. However, telomere length is generally measured in peripheral blood leucocytes rather than in lung tissue, where disease occurs. Consequently, telomere dynamics have not been established for the normal human lung nor for diseased lung tissue. We hypothesized an age- and disease-dependent shortening of lung tissue telomeres.Methods: At time of (re-)transplantation or autopsy, 70 explant lungs were collected: from unused donors (normal, n = 13) and patients with cystic fibrosis (CF, n = 12), chronic obstructive pulmonary disease (COPD, n = 11), chronic hypersensitivity pneumonitis (cHP, n = 9), bronchiolitis obliterans syndrome (BOS) after prior transplantation (n = 11) and restrictive allograft syndrome (RAS) after prior transplantation (n = 14). Lungs were inflated, frozen and then scanned using CT. Four tissue cores from distinct lung regions were sampled for analysis. Disease severity was evaluated using CT and micro CT imaging. DNA was extracted from the samples and average relative telomere length (RTL) was determined using real-time qPCR.Results: The normal lungs showed a decrease in RTL with age (p < 0.0001). Of the diseased lungs, only BOS and RAS showed significant RTL decrease with increasing lung age (p = 0.0220 and p = 0.0272 respectively). Furthermore, we found that RTL showed considerable variability between samples within both normal and diseased lungs. cHP, BOS and RAS lungs had significant shorter RTL in comparison with normal lungs, after adjustment for lung age, sex and BMI (p < 0.0001, p = 0.0051 and p = 0.0301 respectively). When investigating the relation between RTL and regional disease severity in CF, cHP and RAS, no association was found.Conclusion: These results show a progressive decline in telomere length with age in normal, BOS and RAS lungs. cHP, BOS and RAS lungs demonstrated shorter RTL compared to normal lungs. Lung tissue RTL does not associate with regional disease severity within the lung. Therefore, tissue RTL does not seem to fully reflect peripheral blood telomere length. [ABSTRACT FROM AUTHOR]

Background: Telomere attrition is extremely rapid during the first years of life, while lifestyle during adulthood exerts a minor impact. This suggests that early life is an important period in the determination of telomere length. We investigated the importance of the early-life environment on both telomere tracking and adult telomere length.Methods: Among 184 twins of the East Flanders Prospective Twin Survey, telomere length in placental tissue and in buccal cells in young adulthood was measured. Residential addresses at birth and in young adulthood were geocoded and residential traffic and greenness exposure was determined.Results: We investigated individual telomere tracking from birth over a 20 year period (mean age (SD), 22.6 (3.1) years) in association with residential exposure to traffic and greenness. Telomere length in placental tissue and in buccal cells in young adulthood correlated positively (r = 0.31, P < 0.0001). Persons with higher placental telomere length at birth were more likely to have a stronger downward shift in telomere ranking over life (P < 0.0001). Maternal residential traffic exposure correlated inversely with telomere length at birth. Independent of birth placental telomere length, telomere ranking between birth and young adulthood was negatively and significantly associated with residential traffic exposure at the birth address, while traffic exposure at the residential address at adult age was not associated with telomere length.Conclusions: Longitudinal evidence of telomere length tracking from birth to adulthood shows inverse associations of residential traffic exposure in association with telomere length at birth as well as accelerated telomere shortening in the first two decades of life. [ABSTRACT FROM AUTHOR]

• PM 2.5 exposure during pregnancy is associated with the telomere-mitochondrial axis of aging at birth. • Telomere length is a mediator in the association between PM 2.5 and mitochondrial DNA content and p53 protein level. • This study provides insights in the air pollution induced core-axis of aging. • Follow-up studies are needed to investigate PM 2.5 -linked differences in the core-axis of aging in relation to health and disease later in life. Particulate matter (PM) is associated with aging markers at birth, including telomeres and mitochondria. It is unclear whether markers of the core-axis of aging, i.e. tumor suppressor p53 (p53) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), are associated with prenatal air pollution and whether there are underlying mechanisms. 556 mother-newborn pairs from the ENVIR ON AGE birth cohort were recruited at the East Limburg Hospital in Genk (Belgium). In placenta and cord blood, telomere length (TL) and mitochondrial DNA content (mtDNAc) were measured using quantitative real-time polymerase chain reaction (qPCR). In cord plasma, p53 and PGC-1α protein levels were measured using ELISA. Daily ambient PM 2.5 concentrations during gestation were calculated using a spatial temporal interpolation model. Distributed lag models (DLMs) were applied to assess the association between prenatal PM 2.5 exposure and each molecular marker. Mediation analysis was performed to test for underlying mechanisms. A 5 µg/m3 increment in PM 2.5 exposure was associated with −11.23 % (95 % CI: −17.36 % to −4.65 %, p = 0.0012) and −7.34 % (95 % CI: −11.56 % to −2.92 %, p = 0.0014) lower placental TL during the entire pregnancy and second trimester respectively, and with −12.96 % (95 % CI: −18.84 % to −6.64 %, p < 0.001) lower placental mtDNAc during the third trimester. Furthermore, PM 2.5 exposure was associated with a 12.42 % (95 % CI: −1.07 % to 27.74 %, p = 0.059) higher cord plasma p53 protein level and a −3.69 % (95 % CI: −6.97 % to −0.31 %, p = 0.033) lower cord plasma PGC-1α protein level during the third trimester. Placental TL mediated 65 % of the negative and 17 % of the positive association between PM 2.5 and placental mtDNAc and cord plasma p53 protein levels, respectively. Ambient PM 2.5 exposure during pregnancy is associated with markers of the core-axis of aging, with TL as a mediating factor. This study strengthens the hypothesis of the air pollution induced core-axis of aging, and may unravel a possible underlying mediating mechanism in an early-life epidemiological context. [ABSTRACT FROM AUTHOR]

Mitochondria are known to respond to environmental stressors but whether green space is associated with mitochondrial abundance is unexplored. Furthermore, as exposures may affect health from early life onwards, we here evaluate if residential green space is associated with mitochondria DNA content (mtDNAc) in children. In primary schoolchildren (COGNAC study), between 2012 and 2014, buccal mtDNAc was repeatedly (three times) assessed using qPCR. Surrounding low (<3m), high (≥3m) and total (sum of low and high) green space within different radii (100m–1000m) from the residence and distance to the nearest large green space (>0.5ha) were estimated using a remote sensing derived map. Given the repeated measures design, we applied a mixed-effects model with school and subject as random effect while adjusting for a priori chosen fixed covariates. Results: mtDNAc was assessed in 246 children with a total of 436 measurements (mean age 10.3 years). Within a 1000m radius around the residential address, an IQR increment in low (11.0%), high (9.5%), and total (13.9%) green space was associated with a respectively 15.2% (95% CI: 7.2%–23.7%), 10.8% (95% CI: 4.5%–17.5%), and 13.4% (95% CI: 7.4%–19.7%) higher mtDNAc. Conversely, an IQR increment (11.6%) in agricultural area in the same radius was associated with a −3.4% (95% CI: 6.7% to −0.1%) lower mtDNAc. Finally, a doubling in distance to large green space was associated with a −5.2% (95% CI: 7.9 to −2.4%) lower mtDNAc. To our knowledge, this is the first study evaluating associations between residential surrounding green space and mtDNAc in children. Our results showed that green space was associated with a higher mtDNAc in children, which indicates the importance of the early life environment. To what extent these findings contribute to later life health effects should be further examined. [Display omitted] • Residential surrounding green space is associated with higher child mtDNA content. •Exposure to agriculture is associated with lower child mtDNA content. •Living closer to large green space is associated with higher mtDNA content. [ABSTRACT FROM AUTHOR]

Green spaces are associated with increased well-being and reduced risk of developing psychiatric disorders. In this study, we aimed to investigate how residential proximity to green spaces was associated with stress response buffering during the COVID-19 pandemic in a prospective cohort of young mothers. We collected information on stress in 766 mothers (mean age: 36.6 years) from the ENVIR ON AGE birth cohort at baseline of the study (from 2010 onwards), and during the COVID-19 pandemic (from December 2020 until May 2021). Self-reported stress responses due to the COVID-19 pandemic were the outcome measure. Green space was quantified in several radiuses around the residence based on high-resolution (1 m2) data. Using ordinal logistic regression, we estimated the odds of better resistance to reported stress, while controlling for age, socio-economic status, stress related to care for children, urbanicity, and household change in income during the pandemic. In sensitivity analyses we corrected for pre-pandemic stress levels, BMI, physical activity, and changes in health-related habits during the pandemic. We found that for an inter-quartile range contrast in residential green space 300 m and 500 m around the residence, participants were respectively 24% (OR = 1.24, 95%CI: 1.03 to 1.51) and 29% (OR = 1.29, 95%CI: 1.04 to 1.60) more likely to be in a more resistant category, independent of the aforementioned factors. These results remained robust after additionally controlling for pre-pandemic stress levels, BMI, physical activity, smoking status, urbanicity, psychological disorders, and changes in health-related habits during the pandemic. This prospective study in young mothers highlights the importance of proximity to green spaces, especially during challenging times. • Stress responses to the COVID19 pandemic were collected in a prospective cohort of mothers of young children. • Residential proximity to green spaces was quantified using high resolution (1 m2) land cover map data. • Higher residential proximity to green space is associated with a stress buffering effect to increased feelings of stress during the COVID19-pandemic. • The association remained significant after adjusting for baseline pre-pandemic stress levels and other important potential confounders. [ABSTRACT FROM AUTHOR]

Background/aim: Glyphosate, a broad-spectrum herbicide, and its main metabolite aminomethylphosphonic acid (AMPA) are persistent in the environment. Studies showed associations between glyphosate or AMPA exposure and several adverse cellular processes, including metabolic alterations and oxidative stress.Objective: To determine the association between glyphosate and AMPA exposure and biomarkers of biological aging.Methods: We examined glyphosate and AMPA exposure, mtDNA content and leukocyte telomere length in 181 adults, included in the third cycle of the Flemish Environment and Health Study (FLEHSIII). DNA was isolated from leukocytes and the relative mtDNA content and telomere length were determined using qPCR. Urinary glyphosate and AMPA concentrations were measured by Gas Chromatography-Tandem Mass Spectrometry (GC-MS-MS). We used multiple linear regression models to associate mtDNA content and leukocyte telomere length with glyphosate or AMPA exposure while adjusting for confounding variables.Results: A doubling in urinary AMPA concentration was associated with 5.19% (95% CI: 0.49 to 10.11; p = 0.03) longer leukocyte telomere length, while no association was observed with urinary glyphosate concentration. No association between mtDNA content and urinary glyphosate nor AMPA levels was observed.Conclusions: This study showed that AMPA exposure may be associated with telomere biology in adults. [ABSTRACT FROM AUTHOR]

• Chronic exposure to PM 2.5 is associated with lower child buccal telomere length. • Chronic exposure to PM 2.5 is associated with lower child mitochondrial DNA content. • Recent traffic related air pollution is associated with lower child telomere length. Pro-inflammatory conditions such as air pollution might induce biological ageing. However, the available evidence on such an impact in children is still very scarce. We studied in primary schoolchildren the association of ambient residential air pollution exposure with telomere length (TL) and mitochondrial DNA content (mtDNAc), two important targets of the core axis of ageing. Between 2012 and 2014, buccal TL and mtDNAc were repeatedly assessed using qPCR in 197 Belgian primary schoolchildren (mean age 10.3 years) as part of the COGNAC study. At the child's residence, recent (week), sub-chronic (month) and chronic (year) exposure to nitrogen dioxide (NO 2), particulate matter ≤ 2.5 µm (PM 2.5) and black carbon (BC) were estimated using a high resolution spatiotemporal model. A mixed-effects model with school and subject as random effect was used while adjusting for a priori chosen covariates. An interquartile range (IQR) increment (1.9 µg/m3) in chronic PM 2.5 exposure was associated with a 8.9% (95% CI: −15.4 to −1.9%) shorter TL. In contrast to PM 2.5 , chronic exposure to BC and NO 2 was not associated with TL but recent exposure to BC and NO 2 showed significant inverse associations with TL: an IQR increment in recent exposure to BC (0.9 µg/m3) and NO 2 (10.2 µg/m3) was associated with a 6.2% (95% CI: −10.6 to −1.6%) and 6.4% (95% CI: −11.8 to −0.7%) shorter TL, respectively. Finally, an IQR increment in chronic PM 2.5 exposure was associated with a 12.7% (95% CI: −21.7 to −2.6%) lower mtDNAc. However, no significant associations were seen for NO 2 and BC or for other exposure windows. Chronic exposure to PM 2.5 below the EU threshold was associated with child's shorter buccal TL and lower mtDNAc, while traffic-related pollutants (BC and NO 2) showed recent effects on telomere biology. Our data add to the literature on air pollution-induced effects of TL and mtDNAc, two measures part of the core axis of cellular ageing, from early life onwards. [ABSTRACT FROM AUTHOR]

• Studies on prenatal exposure to tobacco and children's LTL and mtDNA are limited. • Maternal cotinine during pregnancy is associated with shorter LTL in children. • Global tobacco exposure is linked to mitochondrial DNA increase in children. • Maternal smoking during pregnancy may induce biological aging from an early age. Telomere length and mitochondrial DNA content are considered biomarkers of cellular aging, oxidative stress, and inflammation, but there is almost no information on their association with tobacco smoke exposure in fetal and early life. The aim of this study was to assess whether prenatal and childhood tobacco exposure were associated with leukocyte telomere length (LTL) and mitochondrial DNA (mtDNA) content in children. As part of a multi-centre European birth cohort study HELIX (Human Early-Life Exposome) (n = 1396) we assessed maternal smoking status during pregnancy through questionnaires, and through urinary cotinine levels that were then used to classify women as not exposed to smoking (<10 µg/L), exposed to secondhand smoke (SHS) (10–50 µg/L) and active smokers (>50 µg/L). When the children were around 8 years of age (range: 5.4–12.0 years), childhood SHS tobacco smoke exposure was assessed through an extensive questionnaire and through measurements of urinary cotinine (<3.03 µg/L non-detected, >3.03 µg/L detected). Leukocyte mtDNA content and LTL were measured in the children at 8 years employing real time polymerase chain reaction (qPCR). Effect estimates were calculated using multivariate linear regression models for prenatal and childhood exposures adjusted for potential confounders. Maternal cotinine levels indicative of SHS exposure during pregnancy were associated with a decrease of 3.90% in LTL in children (95% CI: −6.68, −0.91), compared with non-smoking, whereas the association for maternal cotinine levels indicative of active smoking did not reach statistical significance (−3.24%; 95% CI: −6.59, 0.21). Childhood SHS tobacco exposure was not associated with LTL in children. Global SHS exposure during childhood was associated with an increase of 3.51% (95% CI: 0.78, 6.27) in mtDNA content. Our findings suggest that tobacco smoke exposure during pregnancy, even at SHS levels, may accelerate telomere shortening in children and thus induce biological aging from an early age. [ABSTRACT FROM AUTHOR]