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- W2981496814 abstract "PDS 71: Exposome, Johan Friso Foyer, Floor 1, August 27, 2019, 4:30 PM - 5:30 PM Background: Observations from experimental studies have put forth a “core axis of ageing” involving telomeres, mitochondria, TP53, and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A). In this study, we hypothesized that these hallmarks of ageing in placental tissue are interconnected and influenced by early-life ambient air pollution exposure during pregnancy. Methods: In 680 newborns of the ongoing ENVIRONAGE birth cohort, we measured protein levels of TP53 and PPARGC1A in cord plasma and telomere length and mitochondrial DNA (mtDNA) content in placental tissue. Daily ambient particulate matter with a diameter less than 2.5 μm (PM2.5) was calculated for each participant’s home address using a spatial-temporal interpolation model in combination with a dispersion model. The associations between prenatal PM2.5 exposure and specific hallmarks of ageing were analysed with linear regression models, while accounting for covariates and potential confounders. Results: PM2.5 exposure averaged (SD) 13.5 µg/m3 (2.5) over the entire pregnancy period. A 5-μg/m3 increment in PM2.5 exposure during the 3rd trimester was associated with 13.2% (95%CI, −19.3% to −6.7%) shorter placental telomere length, 11.2% (95% CI: -4.1 to -17.7) lower placental mtDNA content, and 7.4% (95% CI: 2.1 to 13.0%) higher TP53 protein levels. Telomere length and mtDNA content were linked [a 10% shorter telomere length was associated with a 4.8% (95% CI: 3.6 to 6.1%) lower mtDNA content], and we observed a negative trend between TP53 protein levels and telomere length (p=0.08). PPARGC1A protein levels were not associated with mtDNA content. Conclusions: Prenatal air pollution is associated between candidate hallmarks of ageing (telomeres, mitochondria, TP53) in placental tissue. This is the first observational study demonstrating some degree of interconnectedness between master regulators of the molecular circuit linking PM-induced telomere damage and compromised mitochondrial biogenesis." @default.
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- W2981496814 date "2019-10-01" @default.
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- W2981496814 title "Linking mitochondrial and telomere damage in foetal tissue" @default.
- W2981496814 doi "https://doi.org/10.1097/01.ee9.0000607780.55478.41" @default.
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