measures, these 19 subjects actually had a geo- metric mean LTL of 1.39 at the start (vs. 1.27 for the population as a whole) that decreased to 1.02 by the third measure. Although LTL declined on average 2.5% (95% CI, –4.6% to –0.5%) with each year of within-subject change in age, we observed wide variation in the rate of change within subjects, and LTL values of some individuals increased from one measurement to the next. Figure 1 shows the location of the BC monitors contributing to the exposure model and residential locations along with corre- sponding quintile of estimated annual mov- ing-average BC level corresponding to each subject’s first measurement occasion. BC lev- els tend to be higher near downtown Boston. Overall, the mean (± SD) annual BC concen- tration was 0.32 ± 0.20 gμ/m 3, and the mean decreased slightly with each repeated measure (mean first measure, 0.33; mean second meas- ure, 0.30; and mean third measure, 0.26). Adjusting for age and year, we found that an IQR (0.25 gμ/m 3) increase in annual mov- ing-average BC concentration was associated with a 5.8% decrease (95% CI, –10.8% to –0.4%) in LTL (Table 2). After adjusting for additional potential confounders, including educational level, BMI, and several other rel- evant physiologic measures and indicators of health status, the association was similar, equiv- alent to a 5.4% decrease in LTL (95% CI, –10.0% to –0.7%) per IQR increase in BC. After also adjusting for living in an urban area and census-tract-level socioeconomic variables, the association was stronger, a 7.9% decrease in LTL (95% CI, –12.8% to –2.7%) per IQR increase in annual BC. Use of inverse probabil- ity of response weighting to reduce potential selection bias that stems from loss to follow-up resulted in a similar estimate, a 7.6% decrease in LTL (95% CI, –12.8% to –2.1%) per IQR increase in annual BC. We made these same adjustments for the sensitivity analysis and tests for interaction presented below. Restricting the study population to the subjects living within 10 km of the nearest BC monitor (132 subjects, 215 measures) resulted in a stronger association, and an IQR increase in BC was associated with a 9.0% decrease (95% CI, –16.5% to –0.9%) in LTL. We found a significant interaction between annual BC and age ≥ 75 years in their effects on LTL (p = 0.050), and the direction of this interaction suggests that older participants were more susceptible to the effects of BC than those < 75 years of age. We also found a statistically significant interaction between BC and statin treatment (p = 0.050), with no evi- dence of an association between BC and LTL among men on statin medications. Figure 2 plots the point estimates and 95% CIs for the association between LTL and BC according to age group and statin treatment. Discussion Investigating the chronic effects of ambient air pollution, we hypothesized that people exposed to higher levels of combustion par- ticles from mobile sources would have shorter telomeres on the ends of their chro- mosomes. Among 165 never-smoking adults from the NAS cohort, we investigated the association between near-residence annual moving-average concentrations of BC and LTL. Analyzing a total of 270 repeated obser- vations, we found that an IQR increase in BC was associated with a 7.6% decrease in telom- ere length (p = 0.008), adjusting for poten- tial confounders, such as age, education level, BMI, year, several relevant aspects of medical history, living in an urban area, and census- tract-level socioeconomic variables, as well as for loss to follow-up using inverse probability of response weighting. The biology of telomere dynamics sug- gests two main mechanisms by which traffic particles could influence LTL. The first is by influencing the rate of cell replication. The ends of chromosomes progressively shorten as cells undergo division because of the inability of DNA polymerase to replicate the lagging DNA strand to its terminus (Allsopp et al. 1992). Chronic inflammation, for example, is associated with increased numbers of leuko- cytes as well as their more rapid expenditure, both requiring a higher rate of replication of cells up the hierarchy of the hematopoietic Table 2. Association between annual moving-average BC exposure and LTL, expressed as difference in LTL per IQR (0.25 µg/m3) increase in BC concentration (n = 165 subjects). Model Adjusted for age and perioda Plus individual-level covariatesb Plus urbanity and census-tract socioeconomic statusc Plus inverse probability weightingd Observations (n) LTL percent change (95% CI) p-Value 274 270 270 270 –5.8% (–10.8% to –0.4%) –5.4% (–10.0% to –0.7%) –7.9% (–12.8% to –2.7%) –7.6% (–12.8% to –2.1%) 0.036 0.026 0.003 0.008 aAdjusted for baseline age, change in age between measures, and year. bAdditionally adjusted for BMI (quadratic), white blood cell count, percent neutrophils, percent lymphocytes, treatment with statin medication (yes, no), diagno- sis of diabetes (yes, no), fasting blood glucose, and education level (< high school, high school graduate, < 4 years of college, 4 years of college, > 4 years of college). cAdditionally adjusted for National Atlas of the United States urban indicator for residence location, census-tract-level median income, and percentage of population below poverty line. dAdditionally adjusted for potential selection bias due to loss to follow-up by assigning inverse probability of follow-up response weights to follow-up observations during the latter part of the study period (from January 2002 to December 2006). In a logistic model, the response indicator was predicted by covariates from the previous measurement occasion, including telomere length, annual BC, age, BMI, statin use, and education level. Traffic particles may shorten telomeres system. Circulating leukocytes are derived from hematopoietic stem cells, so the lengths of telomeres in an individual’s leukocytes reflect the length of the telomeres in their hematopoietic stem cells, which are shortened by their lifetime of replenishing leukocytes. A second type of mechanism leading to shorter telomeres influences the extent of telomere loss during each replication. For instance, the GGG triplets on telomeres are highly sensi- tive to hydroxyl radicals, and oxidative stress is a major determinant of telomere shortening independent of shortening due to incomplete end replication when stem cells divide to pro- duce new leukocytes (von Zglinicki 2002). A causal interpretation of the association between traffic particles and LTL in our study, therefore, relies on the plausibility that traffic particles could be involved in at least one of these two types of mechanisms. Indeed, inflammation and oxidative stress are central in the current mechanistic under- standing of the cardiovascular health effects of particulate air pollution (Brook et al. 2004; Chahine et al. 2007). Epidemiologic studies, human exposure experiments, animal models, and in vitro studies have provided evidence of inflammatory effects from short-term expo- sures to particles (Donaldson and Tran 2002; O’Neill et al. 2007; Rückerl et al. 2007). Inflammation may also play a role in the chronic effects of air pollution, as suggested C inB 10 e sea 5 r c n iR 0 Q I r pe –5 e c n e fre–10 f i d L%–15 T L < 75 > 75 Age (years) No Yes Statins Figure 2. Modification of the effect of annual moving-average BC concentration on LTL by age and statin treatment: NAS, 1999–2006. Estimated percent differences (95% CIs) associated with an interquartile increase (0.25 µg/m3) in annual BC are shown, adjusted for baseline age; change in age between measures; year; BMI (quadratic); white blood cell count; percent neutrophils; percent lym- phocytes; treatment with statin medication (yes, no); diagnosis of diabetes (yes, no); fasting blood glucose; education level (< high school, high school graduate, < 4 years of college, 4 years of college, > 4 years of college); National Atlas of the United States urban indicator for residence location, census-tract–level median income, and percent- age of population below poverty line; and potential selection bias due to loss to follow-up by inverse probability of follow-up response weighting. Environmental Health Perspectives • volume 118 | number 11 | November 2010 1567