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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]

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]

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]

• 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]