Newborn ribosomal DNA content as a potential early marker of genomic instability and longevity in association with prenatal air pollution exposure

Abstract

BACKGROUND AND AIM: Repetitive regions in the genome, including ribosomal DNA repeats, have essential functions in genome stability. Alterations in ribosomal DNA copy numbers (rDNAcn) associates with genome-wide methylation and gene-expression, and links with longevity, as proposed in the rDNA theory of aging. Prenatal air pollution exposures affect molecular markers of aging that may underly later life health effects. We studied the association between prenatal air pollution exposure and this novel potential aging marker (rDNAc) in newborns. METHODS: Cord blood rDNAcn (45S rDNA) was measured in 177 newborns from the ENVIRONAGE birth cohort using ddPCR. Maternal residential exposure to PM10, PM2.5, NO2, and BC during pregnancy was estimated using a high-resolution spatial-temporal interpolation method. Using multivariable-adjusted distributed lag models, newborn rDNAcn was associated with average weekly air pollution exposures. RESULTS: The mean cord blood rDNAcn was 245 (SD: 64). Higher prenatal exposure to PM10, PM2.5, and NO2 in early to mid-pregnancy (weeks 9-18) was associated with an increase in rDNAcn. Each SD increment in air pollutants was associated with an average increase of 22.5 (95%CI: 5.9 to 35.0) copy numbers. Higher exposure to PM10, PM2.5, NO2, and BC late in pregnancy (weeks 25-35) was strongly associated with a decrease in rDNAcn. Each SD increment in air pollutants was associated with an average decrease of –29.6 (95%CI: –49.9 to –9.4) copy numbers. CONCLUSIONS: We studied for the first time rDNAcn in newborns and show that prenatal air pollution exposure is associated with rDNA repeats at birth. These results add evidence to the impact of air pollution on genome stability and early aging mechanisms. Evaluating the rDNA concept of aging in relation to diseases may further show the link between prenatal air, molecular alterations, and health later in life. KEYWORDS: genome instability, aging, ribosomal DNA copy number, prenatal air pollution