title: Plasminogen activator inhibitor-1 is associated with leukocyte telomere length in American Indians: findings from the Strong Heart Family Study.
abstract: Essentials Plasminogen activator inhibitor-1 (PAI-1) advanced cellular senescence in experiment studies. No population study exists on the association between PAI-1 and biological aging in American Indians. We found cross-sectional and longitudinal associations between higher PAI-1 and shorter telomere length. Our findings suggest a pathway linking PAI-1 with biological aging beyond metabolic factors.
  
  
  
  Background Plasminogen activator inhibitor-1 (PAI-1) promotes cellular aging both in vitro and in vivo. Telomere length is a marker of biological aging. Objectives To examine the cross-sectional and longitudinal associations between plasma PAI-1 and leukocyte telomere length in a large-scale epidemiological study of American Indians. Methods We measured leukocyte telomere length (LTL) and plasma PAI-1 in 2560 American Indians who were free of overt cardiovascular disease (CVD) and participated in the Strong Heart Family Study (SHFS) clinical examination in 2001-2003. LTL and PAI-1 were repeatedly measured in 475 participants who attended SHFS clinical visits in both 2001-2003 and 1998-1999. A generalized estimating equation model was used to examine the cross-sectional and longitudinal associations between PAI-1 and LTL, adjusting for known risk factors. Results A higher level of plasma PAI-1 was negatively associated with shorter age-adjusted LTL (β = -0.023; 95% CI, -0.034 to -0.013). This association was attenuated (β = -0.015; 95% CI, -0.029 to -0.002) after adjustments for demographics, study site, lifestyle (smoking, drinking and physical activity) and metabolic factors (obesity, blood pressure, fasting glucose, insulin, lipids and kidney function). Further adjustment for hsCRP did not change this association (β = -0.015; 95% CI, -0.029 to -0.001). Longitudinal analysis revealed that change in plasma PAI-1 was also inversely associated with change in LTL after adjusting for demographics, follow-up years, lifestyle factors, changes in metabolic factors, baseline levels of PAI-1 and LTL (β = -0.0005; 95% CI, -0.0009 to -0.0001). Conclusions A higher level of plasma PAI-1 was associated with shorter LTL in American Indians. This finding may suggest a potential role of PAI-1 in biological aging among American Indians.
authors.affiliation: Department of Epidemiology, College of Public Health and Health Professions, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: H
authors.identifier: 0000-0001-6277-662X
authors.initials: H
authors.lastname: Peng
authors.affiliation: Center for American Indian Health Research, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: F
authors.initials: F
authors.lastname: Yeh
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.affiliation: Missouri Breaks Industries Research Inc., Eagle Butte, SD, USA.
authors.forename: L G
authors.initials: LG
authors.lastname: Best
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Cole
authors.affiliation: Center for American Indian Health Research, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: E T
authors.initials: ET
authors.lastname: Lee
authors.affiliation: MedStar Health Research Institute, Hyattsville, MD, USA.
authors.forename: B V
authors.initials: BV
authors.lastname: Howard
authors.affiliation: Department of Epidemiology, College of Public Health and Health Professions, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000428:Alcohol Drinking; D001130:Arizona / Q000208:ethnology; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D003430:Cross-Sectional Studies; D015444:Exercise; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007198:Indians, North American; D007328:Insulin / Q000097:blood; D007677:Kidney Function Tests; D007962:Leukocytes / Q000166:cytology*; D008019:Life Style; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009658:North Dakota / Q000208:ethnology; D009765:Obesity / Q000150:complications; D009825:Oklahoma / Q000208:ethnology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D012907:Smoking; D013023:South Dakota / Q000208:ethnology; D016615:Telomere / Q000648:ultrastructure*; D014481:United States; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human
keywords: Indians, South American; aging; fibrinolysis; plasminogen activator inhibitor 1; telomere; thrombosis