The use of chronological age in clinical practice and in aging research is based on the premise that biological aging proceeds at an identical pace for all human beings. Such an approach overlooks the pnncipals of biological diversity. The central hypothesis of this project is that telomere length, as expressed in white blood cells, provides an account additional to chronological age, of variation in vascular aging among human beings. This hypothesis will be tested in the Offspring Study cohort of the Framingham Heart Study. The project will also seek through genome-wide search for genetic regions with large effects on telomere length.
The specific aims of this project are: 1. To examine the relations between telomere length and indices of arterial aging in the previously phenotyped/genotyped Offspring Study cohort of the Framingham Heart Study. The indices of arterial aging include: brachial pulse pressure, central pulse pressure, augmentation index, and carotid-femoral, carotid-radial and carotid-brachial pulse wave velocities; 2. To assess heritability of telomere length and identify genetic loci that explain variation in telomere length. Results would lead to a better understanding of the heterogeneity of vascular aging, test the concept that telomere length may serve as an index of biological aging, and provide information on genetic determinants of telomere length in human beings.
|Aviv, Abraham; Anderson, James J; Shay, Jerry W (2017) Mutations, Cancer and the Telomere Length Paradox. Trends Cancer 3:253-258|
|Boccardi, Virginia; Razdan, Neetu; Kaplunov, Jessica et al. (2015) Stn1 is critical for telomere maintenance and long-term viability of somatic human cells. Aging Cell 14:372-81|
|Mangino, Massimo; Christiansen, Lene; Stone, Rivka et al. (2015) DCAF4, a novel gene associated with leucocyte telomere length. J Med Genet 52:157-62|
|Hunt, Steven C; Kimura, Masayuki; Hopkins, Paul N et al. (2015) Leukocyte telomere length and coronary artery calcium. Am J Cardiol 116:214-8|
|Aviv, Abraham; Kark, Jeremy D; Susser, Ezra (2015) Telomeres, atherosclerosis, and human longevity: a causal hypothesis. Epidemiology 26:295-9|
|Kark, Jeremy D; Nassar, Hisham; Shaham, Dorith et al. (2013) Leukocyte telomere length and coronary artery calcification in Palestinians. Atherosclerosis 229:363-8|
|Aviv, Abraham; Susser, Ezra (2013) Leukocyte telomere length and the father's age enigma: implications for population health and for life course. Int J Epidemiol 42:457-62|
|Mangino, Massimo; Hwang, Shih-Jen; Spector, Timothy D et al. (2012) Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans. Hum Mol Genet 21:5385-94|
|Aviv, Abraham (2012) Genetics of leukocyte telomere length and its role in atherosclerosis. Mutat Res 730:68-74|
|Sanders, Jason L; Fitzpatrick, Annette L; Boudreau, Robert M et al. (2012) Leukocyte telomere length is associated with noninvasively measured age-related disease: The Cardiovascular Health Study. J Gerontol A Biol Sci Med Sci 67:409-16|
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