Increased Susceptibility of Aging Kidney to Ischemic Injury: Identification of Molecular Pathways using Microarray

Aging is associated with an increased incidence and severity of acute renal failure. However, the molecular mechanism(s) underlying the increased susceptibility to injury remain undefined. These experiments were designed to investigate the influence of age on the response of the kidney to ischemic and nephrotoxic challenge. Renal slices were prepared from young (4 month), aged ad libitum (aged-AL; 24 month) and aged caloric restricted (aged-CR; 24 month) male Fischer 344 rats and subjected to ischemic stress (anoxia, 100% N2) for 0-60 min and to cisplatin (2 mM, 4hr) challenge. As assessed by biochemical and histological evaluation, slices from aged-AL rats were more susceptible to injury than young counterparts. Importantly, caloric restriction attenuated the increased susceptibility to injury. In an attempt to identify the molecular pathway(s) underlying this response, microarray analysis was performed on tissue harvested from the same animals used for the functional analysis. RNA was isolated and the corresponding cDNA was hybridized to CodeLink™ Rat Whole Genome Bioarray slides. Subsequent gene expression analysis was performed using GeneSpring software. Using two-sample t-tests and a 2-fold cut-off, the expression of 92 genes was changed during aging and attenuated by caloric restriction. In summary, several changes were identified that may be associated with the increased susceptibility of aging kidney to injury. Keywords: aging, caloric-restriction, kidney This study utilized three groups (young, aged ad libitum, and aged caloric-restricted) each with 4 biological replicates for a total of 12 samples. Each sample was hybridized to a single one-color array platform with no reference samples being used for a total of 12 arrays.