Aging research has undertaken a new dimension as it became evident that telomeres play a key function in cellular senescence. Recent studies strongly suggest that telomere biology is also involved in diseases of human aging. In humans, telomere length is relatively short, longer in women than men, highly heritable, highly variable, and with regard to replicating somatic cells, inversely related to donor age. In addition, after age-adjustment, telomere length is correlated with a number of indices of cardiovascular aging. Telomere attrition rate is accelerated by reactive oxygen species, which are major determinants in aging and diseases associated with aging, including cardiovascular diseases. The ultimate objective of the proposal is to identify genes that determine the length of human telomeres.
The specific aims of this project are: 1. To measure telomere length, as expressed in white blood cells, in individuals from the Family Heart Study - Coronary Calcium Scan (FHS-SCAN); 2. To identify genetic loci harboring genes accounting for telomere length; 3. To investigate candidate genes in regions with evidence for linkage. Results will serve to define genes as determinants of telomere length. Such information would lead to new diagnostic and therapeutic approaches to treat age-related diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG020132-01A2
Application #
6614247
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Mccormick, Anna M
Project Start
2005-07-15
Project End
2009-06-30
Budget Start
2005-07-15
Budget End
2006-06-30
Support Year
1
Fiscal Year
2005
Total Cost
$402,576
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Pediatrics
Type
Schools of Medicine
DUNS #
623946217
City
Newark
State
NJ
Country
United States
Zip Code
07107
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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
Kark, Jeremy D; Goldberger, Nehama; Kimura, Masayuki et al. (2012) Energy intake and leukocyte telomere length in young adults. Am J Clin Nutr 95:479-87
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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