Biomolecular Markers within the Core Axis of Aging and Particulate Air Pollution Exposure in the Elderly: A Cross-Sectional Study

Abstract

Background:Telomere length and mitochondrial DNA (mtDNA) content are markers of aging and aging-related diseases. There is inconclusive evidence concerning the mechanistic effects of airborne particulate matter (PM) exposure on biomolecular markers of aging.Objective:The present study examines the association between short- and long-term PM exposure with telomere length and mtDNA content in the elderly and investigates to what extent this association is mediated by expression of genes playing a role in the telomere–mitochondrial axis of aging.Methods:Among 166 nonsmoking elderly participants, we used qPCR to measure telomere length and mtDNA content in leukocytes and RNA from whole blood to measure expression of SIRT1, TP53, PPARGC1A, PPARGC1B, NRF1, and NFE2L2. Associations between PM exposure and markers of aging were estimated using multivariable linear regression models adjusted for sex, age, BMI, socioeconomic status, statin use, past smoking status, white blood cell count, and percentage of neutrophils. Mediation analysis was performed to explore the role of age-related markers between the association of PM exposure and outcome. Annual PM2.5 exposure was calculated for each participant’s home address using a high-resolution spatial–temporal interpolation model.Results:Annual PM2.5 concentrations ranged from 15 to 23 μg/m3. A 5-μg/m3 increment in annual PM2.5 concentration was associated with a relative decrease of 16.8% (95% CI: –26.0%, –7.4%, p = 0.0005) in telomere length and a relative decrease of 25.7% (95% CI: –35.2%, –16.2%, p < 0.0001) in mtDNA content. Assuming causality, results of the mediation analysis indicated that SIRT1 mediated 19.5% and 22.5% of the estimated effect of PM2.5 exposure on telomere length and mtDNA content, respectively.Conclusions:Our findings suggest that the estimated effects of PM2.5 exposure on the telomere–mitochondrial axis of aging may play an important role in chronic health effects of PM2.5.Citation:Pieters N, Janssen BG, Dewitte H, Cox B, Cuypers A, Lefebvre W, Smeets K, Vanpoucke C, Plusquin M, Nawrot TS. 2016. Biomolecular markers within the core axis of aging and particulate air pollution exposure in the elderly: a cross-sectional study. Environ Health Perspect 124:943–950; http://dx.doi.org/10.1289/ehp.1509728

Identifying sensitive windows for prenatal particulate air pollution exposure and mitochondrial DNA content in cord blood

“…More recently, in an occupational study of truck drivers and office workers in Beijing, China, short term (averaged of 2–8 days) personal exposure to elemental carbon (EC) and PM 10 was associated with lower mtDNA content in all participants (Hou et al 2013). In a panel of elderly people living in Belgium, increased annual PM 2.5 was associated with decreased mtDNA content in blood (Pieters et al 2015). Only one other study has reported on the association between prenatal PM exposure and mitochondrial DNA content in cord blood (Janssen et al 2012).…”

Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

“…As mentioned, the literature examining the relationship between particles and TL has been conflicting. Significant associations between annual PM 2.5 exposures and decreased TL have been reported [45], but in the NAS the relationship between annual BC exposures and decreased TL was only observed in never smokers [11]. The literature concerning short-term particle exposures is even more obscure.…”

“…We selected the 1-year average because it correlates well with averages of PM 2.5 , BC, and temperature over longer time windows and was available for a higher number of participants (Supplementary Table S1). Moreover, existing studies examining relationships between particle exposures and other biological markers of aging, like TL, report more consistent and biologically significant results when a 1-year particle exposure is utilized [6, 11, 45–48]. …”

The Association of Telomere Length in Peripheral Blood Cells with Cancer Risk: A Systematic Review and Meta-analysis of Prospective Studies

“…In addition to chronologic aging, TL is influenced by genetic factors (3) and varies considerably between individuals, even those with the same chronologic age. TL is also affected by numerous environmental factors (4); nutrients, foods, and dietary patterns (5); cigarette smoking (6); air pollution (7); physical activity (6,8); and chronic inflammation (9).…”