The association between ambient particulate matter exposure and the telomere-mitochondrial axis of aging in newborns

Abstract

Background: Particulate matter (PM) is associated with aging markers at birth, including telomeres and mito-chondria. 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-1 alpha), are associated with prenatal air pollution and whether there are underlying mechanisms.Methods: 556 mother-newborn pairs from the ENVIRONAGE 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-1 alpha protein levels were measured using ELISA. Daily ambient PM2.5 concentrations during gestation were calculated using a spatial temporal interpolation model. Distributed lag models (DLMs) were applied to assess the association between prenatal PM2.5 exposure and each molecular marker. Mediation analysis was performed to test for underlying mechanisms. Results: A 5 mu g/m3 increment in PM2.5 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, PM2.5 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-1 alpha protein level during the third trimester. Placental TL mediated 65 % of the negative and 17 % of the positive association between PM2.5 and placental mtDNAc and cord plasma p53 protein levels, respectively.Conclusion: Ambient PM2.5 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.