With the completion of the human genome project, attention is shifting towards individual genetic variation. Such variation, most of which consists of single nucleotide polymorphisms (SNPs), may account for a substantial portion of human individual phenotypic variation, including differences in aging-related characteristics. Especially important are SNPs that affect the function of genes in candidate longevity assurance pathways, since they could provide novel targets for the early detection and possible prevention of aging-related functional decline. Optimal study populations in this respect are those in which aging related phenotypes can be defined in terms of their progression from middle age onwards, rather than as snapshots in time. We hypothesize that genetic variation at loci involved in genome maintenance can be related to individual differences in the rate and severity of aging. To address this hypothesis, a systematic multidisciplinary study is proposed in which SNP haplotypes of about 100 genes in 5 genome maintenance pathways will be determined in individuals of an ongoing longitudinal study of 586 Mexican American (MA) and 428 European American (EA) (SALSA; San Antonio Longitudinal Study of Aging). Subsequent association analysis in conjunction with functional assays of allelic gene variants will provide insight into their biological significance. The results should lead to increased understanding of the role of genome maintenance in healthy aging and provide genetic markers to identify individuals at risk for specific aging related phenotypes. This will open up the possibility of targeted and personalized intervention strategies, ultimately leading to improved quality of life of the elderly population.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG024391-01
Application #
6818326
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5 (M3))
Program Officer
Mccormick, Anna M
Project Start
2004-09-30
Project End
2009-06-30
Budget Start
2004-09-30
Budget End
2005-06-30
Support Year
1
Fiscal Year
2004
Total Cost
$304,615
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Other Basic Sciences
Type
Other Domestic Higher Education
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Ryu, Seungjin; Han, Jeehae; Norden-Krichmar, Trina M et al. (2018) Effective discovery of rare variants by pooled target capture sequencing: A comparative analysis with individually indexed target capture sequencing. Mutat Res 809:24-31
Ryu, Seungjin; Atzmon, Gil; Barzilai, Nir et al. (2016) Genetic landscape of APOE in human longevity revealed by high-throughput sequencing. Mech Ageing Dev 155:7-9
Kato, Kaori; Zweig, Richard; Schechter, Clyde B et al. (2016) Positive attitude toward life, emotional expression, self-rated health, and depressive symptoms among centenarians and near-centenarians. Aging Ment Health 20:930-9
Park, Caroline; Suh, Yousin; Cuervo, Ana Maria (2015) Regulated degradation of Chk1 by chaperone-mediated autophagy in response to DNA damage. Nat Commun 6:6823
Han, Jeehae; Atzmon, Gil; Barzilai, Nir et al. (2015) Genetic variation in Sirtuin 1 (SIRT1) is associated with lipid profiles but not with longevity in Ashkenazi Jews. Transl Res 165:480-1
Ryu, Seungjin; Teles, Francesca; Minopoli, Giuseppina et al. (2015) An epigenomic role of Fe65 in the cellular response to DNA damage. Mutat Res 776:40-7
Xiong, Xing-dong; Jung, Hwa Jin; Gombar, Saurabh et al. (2015) MicroRNA transcriptome analysis identifies miR-365 as a novel negative regulator of cell proliferation in Zmpste24-deficient mouse embryonic fibroblasts. Mutat Res 777:69-78
Cho, Siyoung; Cho, Miook; Kim, Juewon et al. (2015) Syringaresinol protects against hypoxia/reoxygenation-induced cardiomyocytes injury and death by destabilization of HIF-1? in a FOXO3-dependent mechanism. Oncotarget 6:43-55
Schneider, Jaime L; Suh, Yousin; Cuervo, Ana Maria (2014) Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation. Cell Metab 20:417-32
Esterson, Yonah B; Carey, Michelle; Piette, John D et al. (2014) A systematic review of innovative diabetes care models in low-and middle-income countries (LMICs). J Health Care Poor Underserved 25:72-93

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