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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 ENVIR ON AGE 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/m 2 . 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/m 2 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.

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.

Telomere length (TL) is investigated as a biomarker for aging and disease-susceptibility, but measurement using quantitative polymerase chain reaction (qPCR) faces challenges in accuracy and reproducibility. The potential impact of pre-analytical factors on TL measurements remains underexplored. We evaluated the impact of delayed blood processing, a typical feature in population studies. Blood samples from 35 adults were processed for buffy coat extraction either immediately or kept at 4 °C and processed after three and seven days (total n  = 105). After processing, samples were stored at -80 °C. Relative TL was measured via qPCR and expressed as T/S ratio. Strikingly, delayed blood processing led to a significant increase in TL: the mean T/S ratio was 0.886 ± 0.205 at day 0, rising to 1.022 ± 0.240 at day 3 ( p  = 0.03) and to 1.190 ± 0.205 at day 7 ( p  < 0.001), corresponding to increases of 15% and 34%, respectively. Notably, TL correlated inversely with DNA integrity. These findings underscore the critical impact of delayed sample processing on TL measurements, emphasizing the need for consistent pre-analytical protocols to ensure accurate and reliable research outcomes. The impact of our findings is considerable as it may overshadow not only previously reported results but also real biological differences in TL between studied groups of patients.

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.

Background Long-COVID is defined as the persistency or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. Common persistent symptoms are fatigue, sleep disturbances, post-exertional malaise (PEM), pain, and cognitive problems. Long-COVID is estimated to be present in about 65 million people. We aimed to explore clinical and biological factors that might contribute to Long-COVID. Methods Prospective longitudinal cohort study including patients infected with SARS-CoV-2 between March 2020 and March 2022. Patients were assessed between 4 and 12 months after infection at the COVID follow-up clinic at UZ Leuven. We performed a comprehensive clinical assessment (including questionnaires and the 6-min walking test) and biological measures (global DNA methylation, telomere length, mitochondrial DNA copy number, inflammatory cytokines, and serological markers such as C-reactive protein, D-dimer, troponin T). Results Of the 358 participants, 328 were hospitalised, of which 130 had severe symptoms requiring intensive care admission; 30 patients were ambulatory referrals. Based on their clinical presentation, we could identify 6 main clusters. One-hundred and twenty-seven patients (35.4%) belonged to at least one cluster. The bigger cluster included PEM, fatigue, sleep disturbances, and pain ( n  = 57). Troponin T and telomere shortening were the two main markers predicting Long-COVID and PEM-fatigue symptoms. Conclusions Long-COVID is not just one entity. Different clinical presentations can be identified. Cardiac involvement (as measured by troponin T levels) and telomere shortening might be a relevant risk factor for developing PEM-fatigue symptoms and deserve further exploring.

Telomere length (TL) is a recognized biomarker for ageing in multiple species. In dairy cattle, the transition period is considered a very stressful period. We hypothesized that TL shortens during this period. Holstein cows (n = 61) were followed during the transition period. Blood and milk samples were collected at − 7, 3, 6, 9, 21d relative to calving to determine concentrations of oxidative, energetic metabolic, and inflammatory markers. Average relative leukocyte TL was measured by a modified qPCR protocol 7d before and 21d after parturition. We confirmed TL attrition during the transition period (P = 0.02), as TL was 1.05 ± 0.229 (mean ± SD) before, and 0.97 ± 0.191 (mean ± SD) after parturition. Univariable analyses assessed associations between blood markers and TL shortening. Greater plasma oxidative parameters, including oxidized glutathione and glutathione peroxidase, were positively and negatively (respectively) associated with TL attrition. Higher blood α- and β-globulin were all positively associated, while IGF-1, albumin-globulin ratio and albumin were negatively associated with TL attrition. Greater serum amyloid A and haptoglobin were linked with greater TL shortening. This study reveals significant TL shortening during the transition period in dairy cows and identifies significant associations with oxidative stress, metabolic stress, and inflammation. While these associations are observed, no causality can be established. Our findings suggest the need for further research to explore the effects of transition-related stress on TL dynamics.

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 ENVIR ON AGE 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. Graphical Abstract

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.

Background Telomere length is an important indicator of biological age and a complex multi-factor trait. To date, the telomere interactome for comprehending the high-dimensional biological aspects linked to telomere regulation during childhood remains unexplored. Here we describe the multi-omics signatures associated with childhood telomere length. Methods This study included 1001 children aged 6 to 11 years from the Human Early-life Exposome (HELIX) project. Telomere length was quantified via qPCR in peripheral blood of the children. Blood DNA methylation, gene expression, miRNA expression, plasma proteins and serum and urinary metabolites were measured through microarrays or (semi-) targeted assays. The association between each individual omics feature and telomere length was assessed in omics-wide association analyses. In addition, a literature-guided, sparse supervised integration method was applied to multiple omics, and latent components were extracted as predictors of child telomere length. The association of these latent components with early-life aging risk factors (child lifestyle, body mass index (BMI), exposure to smoking, etc.), were interrogated. Results After multiple-testing correction, only two CpGs (cg23686403 and cg16238918 at PARD6G gene) out of all the omics features were significantly associated with child telomere length. The supervised multi-omics integration approach revealed robust associations between latent components and child BMI, with metabolites and proteins emerging as the primary contributing features. In these latent components, the contributing molecular features were known as involved in metabolism and immune regulation-related pathways. Conclusions Findings of this multi-omics study suggested an intricate interplay between telomere length, metabolism and immune responses, providing valuable insights into the molecular underpinnings of the early-life biological aging.

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-ND4L 10550A>G heteroplasmy has been associated with BMI in adults. Therefore, we hypothesized that in utero PM 2.5 exposure is associated with cord blood MT-ND4L 10550A>G heteroplasmy and early life growth. In addition, the role of cord blood MT-ND4L 10550A>G heteroplasmy in overweight during early childhood is investigated. Methods This study included 386 mother-newborn pairs. Outdoor PM 2.5 concentrations were determined at the maternal residential address. Cord blood MT-ND4L 10550A>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 PM 2.5 exposure on childhood overweight mediated by cord blood MT-ND4L 10550A>G heteroplasmy. Results Prenatal PM 2.5 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 PM 2.5 exposure was associated with cord blood MT-ND4L 10550A>G heteroplasmy from gestational week 9 – 13. The largest effect was observed in week 10, where a 5 µg/m 3 increment in PM 2.5 was linked with cord blood MT-ND4L 10550A>G heteroplasmy (OR = 0.93; 95% CI: 0.87 to 0.99). Cord blood MT-ND4L 10550A>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 PM 2.5 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-ND4L 10550A>G heteroplasmy. Conclusions Cord blood MT-ND4L 10550A>G heteroplasmy was linked with childhood overweight. In addition, in utero exposure to PM 2.5 during the first trimester of pregnancy was associated with cord blood MT-ND4L 10550A>G heteroplasmy in newborns. Our analysis did not reveal any mediation of cord blood MT-ND4L 10550A>G heteroplasmy in the association between PM 2.5 exposure and childhood overweight.