Raymond Yung photo

Leukocyte-endothelial cell interaction in aging

a MiCDA Research Project Description

Investigators: Raymond Yung, Bruce C. Richardson

Funding: National Institute on Aging, 2010-2016 (2 R01 AG 020628 06 A2)

It has become increasingly apparent that epigenetics, where the genome
interacts with the environment, is central to our understanding of the relationship
between aging and disease. DNA methylation is a key epigenetic mechanism
controlling gene expression. Recent data suggest that there is a considerable
epigenetic ?drift? in aging, resulting in relative DNA hypomethylation in many
tissues including T cells. The original RO1 was funded to examine the effect of
aging on the epigenetic control of leukocyte chemokine system. We showed that
aging is associated with increase T cell pro-inflammatory chemokine function that
is at least in part controlled by DNA methylation. In this competing renewal, we
will determine if the aging changes can be ameliorated by altering the T cell
epigenome during the critical stages of immune system development. We
hypothesize that the prenatal `epigenetic environment? can modify T cell
chemokine receptor response that in turn determines the late-life susceptibility to
chronic inflammatory diseases. Specific Aim 1 will determine the effect of the prenatal
methyl-donor supplementation diet on murine T cell chemokine function
throughout the life span. Specific Aim 2 will assess the consequence of dietinduced
epigenetic changes on the heritable risk of coronary artery disease.

Research Signature Theme:

Aging, Genetics, and Social Science