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AGE-RELATED SUSCEPTIBILITY: A GENOMICS APPROACH.
Citation:
Royland, J E. AGE-RELATED SUSCEPTIBILITY: A GENOMICS APPROACH. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
By the year 2030 more than 70 million Americans will be over the age of 65. These older adults are a subpopulation that may have special susceptibility to toxic insult due to critical characteristics of their life-stage. Current EPA testing guidelines do not identify the elderly as a special at risk group, however new initiatives have been implemented that focus research on this segment of the population. Monitoring global patterns of gene expression by microarray analysis allows one to examine multiple physiological mechanisms simultaneously. Our efforts are focused on pathways important in toxicological assessment. That is, pathways involved in ROS generation and elimination, enzymes involved in DNA maintenance and repair and genes that have wide ranging function in regulation of cell processes such as cell adhesion molecules, transcription factors and proteins in key signal transduction pathways. We used a commercial rat toxicology array (Atlas Rat Toxicology 1.2 from Clontech) to examine steady state expression levels of genes that have the potential to contribute to susceptibility. Hippocampus and striatum, brain areas associated with deficits in the aged, from the brains of non-dosed young (3 mos) and aged (23 mos) male Fisher rats were compared. Over 150 genes were found to be differentially expressed between the two age groups. Our data analysis concentrates on identifying and interpreting expression profiles in the different brain areas to determine potential region specific, age-related sensitivities. This abstract does not necessarily reflect US EPA policy.