Genotype-by-age interaction and identification of longevity-associated genes from microarray data

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Abstract
Microarray-based comparisons of long-lived and normal mouse strains represent a promising approach for dissecting the basis of lifespan extension in higher organisms. Recently, Boylston et al. ( 2006 ) generated a genome-wide data set that allowed expression levels of Snell (Pit1 dw/dw ) and Ames (Prop1 df/df ) long-lived mice to be compared with age-matched control mice across different ages (6–24 months). Longevity-associated genes were identified as those genes exhibiting differential expression between long-lived and normal mice at every age examined. In this communication, an alternative approach to identifying longevity-associated genes is suggested and applied to the data sets considered by Boylston et al. ( 2006 ). Longevity-associated genes are defined as those exhibiting significant genotype-by-age interaction with respect to expression levels of long-lived and normal mice, and a total of 63 longevity-associated genes are identified. This approach may lend greater confidence to the inference that expression of identified genes specifically underlies aging differences between long-lived and normal genotypes.