Vascular aging (VA) is the progressive vascular remodeling and alteration of vascular structure that accompanies biological aging. VA results in an increase in artery stiffness, accompanied by impairment of endothelial regeneration and shortening of leukocyte telomere length (LTL). The progress of VA in early age strongly predicts the occurrence of CVD, the leading cause of death in old age. This progress is determined in part by genetic factors, with effects modifiable by exposure to various non-genetic factors. The overall objective of this proposal is to identify genetic components with modest-to-large longitudinal effects on the progress of VA from childhood, and to investigate the association of genetic components with circulating endothelial progenitor cells (EPCs) and leukocyte telomere length (LTL) that represent endothelial regeneration and biological aging respectively.
Our specific aims are to: (1) Identify genomic linkage regions and candidate genes underlying VA. The hypotheses are that one or more chromosome regions exert modest-to-large, heritable genetic effects on VA phenotypes from early childhood, and that some candidate genes exert modest-to-large effects but lack detectable heritability. (2) Determine common and rare effect variants at the genomic linkage regions and candidate genes identified in Specific Aim 1 that are associated with VA, endothelial regeneration and biological aging. The hypotheses are that genetic determinants underlying VA phenotypes are related to circulating EPCs and LTL, and rare functional variants in five important candidate genes are associated with longitudinal VA phenotypes in the upper and lower 5% of BHS participants. (3) Validate significant findings from Specific Aim 2 in a replication sample. The hypothesis is that the findings of common and rare effect variants will be repeated in a random populationbased sample and are associated with healthy aging. It is expected that identification of effect variants underlying VA will be important for defining genetic predisposition to vascular aging or healthy aging later in life.

Public Health Relevance

The proposed study has important clinical and public health implications. It will provide a more complete understanding of the link between vascular aging in early life and CVD effects and healthy aging in later life. This will thus provide us the means for devising strategies to prevent VA and increase the chances of living to a successful old age.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1-RI-B (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Tulane University
New Orleans
United States
Zip Code
Guo, Weichao; Saito, Shigeki; Sanchez, Cecilia G et al. (2017) TGF-?1 stimulates HDAC4 nucleus-to-cytoplasm translocation and NADPH oxidase 4-derived reactive oxygen species in normal human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol 312:L936-L944
Liao, Wenjuan; Liu, Hongbing; Zhang, Yiwei et al. (2017) Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism. Sci Rep 7:9020
Jazwinski, S Michal; Kim, Sangkyu (2017) Metabolic and Genetic Markers of Biological Age. Front Genet 8:64
Palozola, Katherine C; Donahue, Greg; Liu, Hong et al. (2017) Mitotic transcription and waves of gene reactivation during mitotic exit. Science 358:119-122
Jazwinski, S Michal; Jiang, James C; Kim, Sangkyu (2017) Adaptation to metabolic dysfunction during aging: Making the best of a bad situation. Exp Gerontol :
Motherwell, Jessica M; Azimi, Mohammad S; Spicer, Kristine et al. (2017) Evaluation of Arteriolar Smooth Muscle Cell Function in an Ex Vivo Microvascular Network Model. Sci Rep 7:2195
Sweat, Richard S; Sloas, David C; Stewart, Scott A et al. (2017) Aging is associated with impaired angiogenesis, but normal microvascular network structure, in the rat mesentery. Am J Physiol Heart Circ Physiol 312:H275-H284
Kim, Sangkyu; Myers, Leann; Wyckoff, Jennifer et al. (2017) The frailty index outperforms DNA methylation age and its derivatives as an indicator of biological age. Geroscience 39:83-92
Azimi, Mohammad S; Motherwell, Jessica M; Murfee, Walter L (2017) An Ex Vivo Method for Time-Lapse Imaging of Cultured Rat Mesenteric Microvascular Networks. J Vis Exp :
Molinski, Steven V; Shahani, Vijay M; MacKinnon, Stephen S et al. (2017) Computational proteome-wide screening predicts neurotoxic drug-protein interactome for the investigational analgesic BIA 10-2474. Biochem Biophys Res Commun 483:502-508

Showing the most recent 10 out of 65 publications