@article {922, title = {Leukocyte telomere length and cardiovascular disease in the cardiovascular health study.}, journal = {Am J Epidemiol}, volume = {165}, year = {2007}, month = {2007 Jan 01}, pages = {14-21}, abstract = {

The telomere length of replicating somatic cells is inversely correlated with age and has been reported to be associated cross-sectionally with cardiovascular disease (CVD). Leukocyte telomere length, as expressed by mean terminal restriction fragment (TRF) length, was measured in 419 randomly selected participants from the Cardiovascular Health Study, comprising a community-dwelling cohort recruited in four US communities. The authors investigated associations between TRF length and selected measures of subclinical CVD/risk factors for CVD (data were collected at the 1992/1993 clinic visit) and incident CVD (ascertained through June 2002). In these participants (average age = 74.2 years (standard deviation, 5.2)), mean TRF length was 6.3 kilobase pairs (standard deviation, 0.62). Significant or borderline inverse associations were found between TRF length and diabetes, glucose, insulin, diastolic blood pressure, carotid intima-media thickness, and interleukin-6. Associations with body size and C-reactive protein were modified by gender and age, occurring only in men and in participants aged 73 years or younger. In younger (but not older) participants, each shortened kilobase pair of TRF corresponded with a threefold increased risk of myocardial infarction (hazard ratio = 3.08, 95\% confidence interval: 1.22, 7.73) and stroke (hazard ratio = 3.22, 95\% confidence interval: 1.29, 8.02). These results support the hypotheses that telomere attrition may be related to diseases of aging through mechanisms involving oxidative stress, inflammation, and progression to CVD.

}, keywords = {Aged, Cardiovascular Diseases, DNA, Female, Humans, Inflammation, Leukocytes, Male, Myocardial Infarction, Oxidative Stress, Pilot Projects, Polymorphism, Restriction Fragment Length, Risk, Risk Assessment, Risk Factors, Telomere}, issn = {0002-9262}, doi = {10.1093/aje/kwj346}, author = {Fitzpatrick, Annette L and Kronmal, Richard A and Gardner, Jeffrey P and Psaty, Bruce M and Jenny, Nancy S and Tracy, Russell P and Walston, Jeremy and Kimura, Masyuki and Aviv, Abraham} } @article {1088, title = {Insulin-like growth factors and leukocyte telomere length: the cardiovascular health study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {64}, year = {2009}, month = {2009 Nov}, pages = {1103-6}, abstract = {

The insulin-like growth factor (IGF) axis may affect immune cell replicative potential and telomere dynamics. Among 551 adults 65 years and older, leukocyte telomere length (LTL), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-binding proteins 1 and 3 (IGFBP-1, IGFBP-3) were measured. Multivariate linear regression was used to model the association of LTL with IGF-1 and IGFBPs, while controlling for confounding and increasing precision by adjusting for covariates. We observed a significant association between higher IGF-1 and longer LTL after adjustment for age, sex, race, smoking status, body mass index, hypertension, diabetes, and serum lipids. The results suggested an increase of .08 kb in LTL for each standard deviation increase of IGF-1 (p = .04). IGFBP-1 and IGFBP-3 were not significantly associated with LTL. High IGF-1 may be an independent predictor of longer LTL, consistent with prior evidence suggesting a role for IGF-1 in mechanisms relating to telomere maintenance.

}, keywords = {Aged, Aging, Cross-Sectional Studies, Female, Humans, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor Binding Proteins, Insulin-Like Growth Factor I, Leukocytes, Linear Models, Male, Sex Characteristics, Telomere}, issn = {1758-535X}, doi = {10.1093/gerona/glp036}, author = {Kaplan, Robert C and Fitzpatrick, Annette L and Pollak, Michael N and Gardner, Jeffrey P and Jenny, Nancy S and McGinn, Aileen P and Kuller, Lewis H and Strickler, Howard D and Kimura, Masayuki and Psaty, Bruce M and Aviv, Abraham} } @article {1192, title = {Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology.}, journal = {Proc Natl Acad Sci U S A}, volume = {107}, year = {2010}, month = {2010 May 18}, pages = {9293-8}, abstract = {

Telomeres are engaged in a host of cellular functions, and their length is regulated by multiple genes. Telomere shortening, in the course of somatic cell replication, ultimately leads to replicative senescence. In humans, rare mutations in genes that regulate telomere length have been identified in monogenic diseases such as dyskeratosis congenita and idiopathic pulmonary fibrosis, which are associated with shortened leukocyte telomere length (LTL) and increased risk for aplastic anemia. Shortened LTL is observed in a host of aging-related complex genetic diseases and is associated with diminished survival in the elderly. We report results of a genome-wide association study of LTL in a consortium of four observational studies (n = 3,417 participants with LTL and genome-wide genotyping). SNPs in the regions of the oligonucleotide/oligosaccharide-binding folds containing one gene (OBFC1; rs4387287; P = 3.9 x 10(-9)) and chemokine (C-X-C motif) receptor 4 gene (CXCR4; rs4452212; P = 2.9 x 10(-8)) were associated with LTL at a genome-wide significance level (P < 5 x 10(-8)). We attempted replication of the top SNPs at these loci through de novo genotyping of 1,893 additional individuals and in silico lookup in another observational study (n = 2,876), and we confirmed the association findings for OBFC1 but not CXCR4. In addition, we confirmed the telomerase RNA component (TERC) as a gene associated with LTL (P = 1.1 x 10(-5)). The identification of OBFC1 through genome-wide association as a locus for interindividual variation in LTL in the general population advances the understanding of telomere biology in humans and may provide insights into aging-related disorders linked to altered LTL dynamics.

}, keywords = {Cohort Studies, Genome-Wide Association Study, Genotype, Humans, Leukocytes, Polymorphism, Single Nucleotide, Receptors, CXCR4, Telomere, Telomere-Binding Proteins}, issn = {1091-6490}, doi = {10.1073/pnas.0911494107}, author = {Levy, Daniel and Neuhausen, Susan L and Hunt, Steven C and Kimura, Masayuki and Hwang, Shih-Jen and Chen, Wei and Bis, Joshua C and Fitzpatrick, Annette L and Smith, Erin and Johnson, Andrew D and Gardner, Jeffrey P and Srinivasan, Sathanur R and Schork, Nicholas and Rotter, Jerome I and Herbig, Utz and Psaty, Bruce M and Sastrasinh, Malinee and Murray, Sarah S and Vasan, Ramachandran S and Province, Michael A and Glazer, Nicole L and Lu, Xiaobin and Cao, Xiaojian and Kronmal, Richard and Mangino, Massimo and Soranzo, Nicole and Spector, Tim D and Berenson, Gerald S and Aviv, Abraham} } @article {1265, title = {Leukocyte telomere length and mortality in the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {66}, year = {2011}, month = {2011 Apr}, pages = {421-9}, abstract = {

BACKGROUND: Leukocyte telomere length (LTL) is related to diseases of aging, but studies of mortality have been inconsistent.

METHODS: We evaluated LTL in relation to total mortality and specific cause of death in 1,136 participants of the Cardiovascular Health Study who provided blood samples in 1992-1993 and survived through 1997-1998. LTL was measured by Southern blots of the terminal restriction fragments. Cause of death was classified by a committee of physicians reviewing death certificates, medical records, and informant interviews.

RESULTS: A total of 468 (41.2\%) deaths occurred over 6.1 years of follow-up in participants with mean age of 73.9 years (SD 4.7), 65.4\% female, and 14.8\% African American. Although increased age and male gender were associated with shorter LTLs, African Americans had significantly longer LTLs independent of age and sex (p < .001). Adjusted for age, sex, and race, persons with the shortest quartile of LTL were 60\% more likely to die during follow-up than those within the longest quartile (hazard ratio: 1.61, 95\% confidence interval: 1.22-2.12, p = .001). The association remained after adjustment for cardiovascular disease risk factors. Evaluations of cause of death found LTL to be related to deaths due to an infectious disease etiology (hazard ratio: 2.80, 95\% confidence interval: 1.32-5.94, p = .007), whereas a borderline association was found for cardiac deaths (hazard ratio: 1.82, 95\% confidence interval: 0.95-3.49, p = .07) in adjusted models. Risk estimates for deaths due to cancer, dementia, and ischemic stroke were not significant.

CONCLUSION: These data weakly corroborate prior findings of associations between LTL and mortality in the elderly.

}, keywords = {Aged, Aged, 80 and over, Aging, Body Mass Index, Cardiovascular Diseases, Cause of Death, Comorbidity, Coronary Disease, Diabetes Mellitus, Female, Humans, Hypertension, Leukocytes, Longitudinal Studies, Male, Prospective Studies, Smoking, Stroke, Telomere}, issn = {1758-535X}, doi = {10.1093/gerona/glq224}, author = {Fitzpatrick, Annette L and Kronmal, Richard A and Kimura, Masayuki and Gardner, Jeffrey P and Psaty, Bruce M and Jenny, Nancy S and Tracy, Russell P and Hardikar, Sheetal and Aviv, Abraham} }