Research Annual Ambient Black Carbon Associated with Shorter Telomeres in Elderly Men: Veterans Affairs Normative Aging Study John McCracken,1 Andrea Baccarelli,1,2,3 Mirjam Hoxha,2,3 Laura Dioni,2,3 Steve Melly,1 Brent Coull,4 Helen Suh,1 Pantel Vokonas,5,6 and Joel Schwartz1 1Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA; 2Center of Molecular and Genetic Epidemiology, IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Maggiore Hospital, Milan, Italy; 3Department of Environmental and Occupational Health, University of Milan, Milan, Italy; 4Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA; 5Veterans Affairs Outpatient Clinic, Boston, Massachusetts, USA; 6Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA (p = 0.050). mobile traffic. Background : Telomere length reflects biological age and is inversely associated with risk of cardiovascular disease (CVD). Ambient air pollution is associated with CVD, but its effect on telomere length is unknown. o Bjective : We investigated whether ambient black carbon (BC), a marker for traffic-related particles, is associated with telomere length in the Normative Aging Study (NAS). Methods : Among 165 never-smoking men from the NAS, leukocyte telomere length (LTL) was measured repeatedly approximately every 3 years from 1999 through 2006 using quantitative real- time polymerase chain reaction (qRT-PCR). BC concentration at their residences during the year before each LTL measurement was estimated based on a spatiotemporal model calibrated with BC measurements from 82 locations within the study area. r esult : The median [interquartile range (IQR)] annual moving-average BC concentration was 0.32 (0.20–0.45) µg/m3. LTL, expressed as population-standardized ratio of telomere repeat to single-copy gene copy numbers, had a geometric mean (geometric SD) of 1.25 (1.42). We used linear mixed-effects models including random subject intercepts and adjusted for several potential confounders. We used inverse probability of response weighting to adjust for potential selection bias due to loss to follow-up. An IQR increase in annual BC (0.25 µg/m3) was associated with a 7.6% decrease (95% confidence interval, –12.8 to –2.1) in LTL. We found evidence of effect modification, with a stronger association among subjects ≥ 75 years of age compared with younger participants (p = 0.050) and statin medications appearing protective of the effects of BC on LTL c onclusi : Telomere attrition, linked to biological aging, may be associated with long-term exposures to airborne particles, particularly those rich in BC, which are primarily related to auto- words k ey : air pollution, biological aging, cardiovascular physiology, environmental exposure, epigenetic process, particles, traffic, vehicle emissions. Environ Health Perspect 118:1564–1570 (2010). doi:10.1289/ehp.0901831 [Online 17 August 2010] control (Pope et al. 1999), and modification of epigenetic processes (Baccarelli et al. 2009). Investigation of the potential biological mech- anisms underlying chronic health effects has been limited. Telomere attrition, a predictor of CVD that reflects biological aging and the cumulative effects of oxidative stress, is a plau- sible mediator of the chronic health effects of air pollution. One previous study found that traffic officers had shorter leukocyte telom- eres than did office workers and that occu- pational exposures to benzene and toluene were inversely associated with telomere length (Hoxha et al. 2009). We are unaware of any study on the association between typical expo- sures to fine ambient particles and telomere length in a general population. In this study, we use longitudinal data from the Normative Aging Study (NAS) to investigate whether ambient concentration of black carbon (BC), primarily represent- ing mobile source particles, outside an indi- vidual’s home during the previous year was associated with telomere length. Materials and Methods NAS subjects. The NAS is an investigation of aging established in 1963 by the U.S. Department of Veterans Affairs, and all sub- jects were free of chronic disease at the time of recruitment. The present study is restricted to a subset of the 880 persons still partici- pating between 1 January 1999 (when DNA collection began) and 31 December 2006, during which period health and risk factors Address correspondence to J. McCracken, Department of Environmental Health, Harvard School of Public Health, Landmark Building, 415 West, 401 Park Dr., Boston MA 02215 USA. Telephone: (617) 384-8754. Fax: (617) 384-8745. E-mail: jmccrack@hsph.harvard.edu The Veterans Affairs Normative Aging Study, supported by the Cooperative Studies Program/ Epidemiology Research and Information Center of U.S. Department of Veterans Affairs, is a research com- ponent of the Massachusetts Veterans Epidemiological Research and Information Center. This work was also supported by U.S. Environmental Protection Agency awards R827353 and R832416 and by National Institutes of Health awards R01-ES015172, ES014663, ES-0002, and ES009825. The authors declare they have no actual or potential competing financial interests. Received 15 December 2009; accepted 17 August 2010. ovlume 118 | number 11 | November 2010 • Environmental Health Perspectives Telomeres are regions of noncoding DNA at the end of chromosomes that protect against structural degradation, inappropriate recombi- nation, and end-to-end fusion of chromosomes (Blackburn 2001; Wong and Collins 2003). Telomere length declines with each successive cell division and thus serves as a measure of biological aging (Aviv 2002). Shorter telom- eres are associated with greater risk of various chronic diseases, including diabetes (Fitzpatrick et al. 2007), hypertension (Fitzpatrick et al. 2007; Perez-Rivero et al. 2006; Yang et al. 2009), atherosclerosis (Benetos et al. 2004), coronary artery disease (Brouilette et al. 2007; Mukherjee et al. 2009), and heart failure (van der Harst et al. 2007). Evidence from in vitro studies (Honda et al. 2001; Saretzki and Von Zglinicki 2002; von Zglinicki 2002) and human studies (Fitzpatrick et al. 2007; Saretzki and Von Zglinicki 2002) suggests that oxidative stress and inflammation accelerate telomere shortening. These findings have motivated investigation of whether envi- ronmental factors that influence oxidative and inflammatory responses also decrease telomere 1564 length. Telomeres are shorter among people who smoke (McGrath et al. 2007; Morla et al. 2006; Valdes et al. 2005), consume more processed red meat (Nettleton et al. 2008), are obese or gain weight during adulthood (Kim et al. 2009), or live a sedentary lifestyle (Cherkas et al. 2008), leading to the general conclusion that one mechanism by which these factors influence cardiovascular disease (CVD) risk is by accelerating the biological aging of cells, revealed in part by shorter telomeres. Associations between ambient air pollu- tion—both short-term episodes and long-term exposures—and CVD have been observed in numerous epidemiological studies, and systemic inflammation and oxidative stress are central components of hypothesized bio- logical mechanisms (Brook et al. 2004). The mechanisms leading to the short-term effects of CVD have been investigated intensively in recent years and include increased sys- temic inflammation (Schwartz 2001), blood coagulation (Baccarelli et al. 2007, 2008b; Seaton et al. 1999), arterial vasoconstriction (Brook et al. 2002), alteration of autonomic