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Association Study

Aging is a complex process defined by the gradual decline of a multitude of physiological functions leading to an increasing probability of death and thus best studied using a systems biology approach. We are studying aging of the human kidney, which begins to show functional decline around age 40. Kidneys age at different rates, such that some people show little or no effects of aging whereas others show rapid functional decline of the kidney. We first performed whole-genome transcriptional profiling to find genes that change expression with age in the kidney. Such age-regulated genes include components of the mitochondrial electron transport chain, extracellular matrix, and ribosome. Furthermore, the expression profile for kidney aging marks physiological age and not just chronological age. The gene expression profiles distinguish between individuals with rapid or slow kidney aging rates. Some elderly patients showed rapid renal aging, and these patients also exhibited gene expression profiles that were advanced for their age. Conversely, other kidney samples aged slowly and these kidney samples had gene expression profiles similar to those from much younger patients. We are now using these age-regulated genes as candidates in a genetic association study for kidney aging. Our goal is to find SNPs whose alleles associate with different rates of kidney aging. These studies may provide the first evidence for genes that are associated with kidney aging in humans. Not only will this research uncover basic principles about human kidney aging, but it will also be directly relevant to understanding why some people progress to end stage renal disease whereas others do not. The kidney aging genes could help determine the rate of kidney aging for patients, and mechanistic insight from our studies could eventually lead to treatments that slow down or prevent kidney failure in old age.

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