Aging Cell (2008) 7, pp451–458 Doi: 10.1111/j.1474-9726.2008.00397.x BLlackwel ePublishinguLtdkocyte telomeres are longer in African Americans than in whites: the National Heart, Lung, and Blood Institute Family Heart Study and the Bogalusa Heart Study Steven C. Hunt,1 Wei Chen,2 Jeffrey P. Gardner,3 Masayuki Kimura,3 Sathanur R. Srinivasan,2 John H. Eckfeldt,4 Gerald S. Berenson2 and Abraham Aviv3 1Cardiovascular Genetics Division, University of Utah School of Medicine, Salt Lake City, UT, USA (NHLBI Family Heart Study) 2Tulane Center for Cardiovascular Health, Tulane University Health Sciences Center, New Orleans, LA, USA (The Bogalusa Heart Study) 3Center of Human Development and Aging, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA 4Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA (NHLBI Family Heart Study) Summary Leukocyte telomere length (LTL) is ostensibly a bio- indicator of human aging. Here we report that African Americans have longer LTL than whites. We studied cross- sectionally 2453 individuals from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study (age = 30–93 years) and the Bogalusa Heart Study (age = 19–37 years), comprising 1742 whites and 711 Afri- can Americans. We measured LTL by Southern blots of the terminal restriction fragments length. In 234 participants, telomere repeats were also measured by quantitative polymerase chain reaction (qPCR). Adjusted for age and body mass index (BMI), the respective leukocyte telomere lengths (mean ± SEM) were considerably longer in African Americans than in whites both in the Family Heart Study (7.004 ± 0.033 kb vs. 6.735 ± 0.024 kb, p < 0.0001) and the Bogalusa Heart Study (7.923 ± 0.063 kb vs. 7.296 ± 0.039 kb, p < 0.0001). We confirmed the racial effect on LTL by qPCR (3.038 ± 0.565 T/S units for African Americans vs. 2.714 ± 0.487 T/S units for whites, p < 0.001). Cross-sectionally, sex- and BMI-adjusted LTL became shorter with age (range Correspondence Abraham Aviv, Center of Human Development and Aging, Room F-464, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103, USA, Tel.: 973 972 5280; fax: 973 972 5576; e-mail: avivab@umdnj.edu Accepted for publication 01 March 2008 Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2·5, which does not permit commercial exploitation. 19–93 years) at a steeper slope in African Americans than in whites (0.029 kb year–1 vs. 0.020 kb year–1, respectively, p = 0.0001). We suggest that racial difference in LTL arises from a host of interacting biological factors, including replication rates of hematopoietic stem cells. Key words: age; demography; gender; leukocyte; race; telomere. Introduction Mounting evidence suggests that leukocyte telomere length (LTL) is a bio-indicator of human aging, cardiovascular aging in particular. LTL is heritable (Slagboom et al., 1994; Jeanclos et al., 2000; Vasa-Nicotera et al., 2005; Andrew et al., 2006), although it is unknown how much of this heritability relates to birth LTL and the rate of its shortening from birth onward. Age-dependent LTL shortening is due to successive divisions of hematopoietic stem cells (HSCs) and progenitor cells (PCs) that form peripheral leukocytes. Inflammation and oxidative stress – two central elements in the biology of aging and aging-related diseases (Finch & Crimmins, 2004; Balaban et al., 2005) – were reported to be associated with LTL (Aviv et al., 2006a; Demissie et al., 2006; Bekaert et al., 2007; Fitzpatrick et al., 2007). Inflammation entails an increase in number and diminished biological life of leukocyte subsets in the circulation, which would heighten the demand on HSCs/PCs to replicate, a phenomenon expressed in an accelerated telomere attrition and ultimately shortened LTL. Oxidative stress heightens the loss of telomere repeats per cell division (Sitte et al., 1998; Saretzki et al., 1999; Tchirkov & Lansdorp, 2003). The compounded effect of inflam- mation/oxidative stress on the paces of both aging and LTL attrition conceivably explains the shortened LTL observed in individuals with aging-related diseases, particularly atherosclerotic cardiovascular (CV) disease (Brouilette et al., 2003; Cawthon et al., 2003; Benetos et al., 2004; Martin-Ruiz et al., 2005; Matsubara et al., 2006; Brouilette et al., 2007; Fitzpatrick et al., 2007; van der Harst et al., 2007), which is strongly linked to inflammation (Hansson & Libby, 2006). The paradigm that links LTL to CV disease draws on data derived mainly from non-African American populations. But the developmental pattern of CV disease differs between African Americans and whites. For instance, African Americans are more prone to heart failure due to hypertension (Yancy, 2005; Whittle et al., 2006), but they have considerably less coronary © 2008 The Authors Journal compilation © Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland 2008 451