Figure 9

Relationship between caloric restriction and aging in liver, heart, muscle and the central nervous system. Association between differential expression signatures. The association between CR and aging was evaluated for the (A) liver, (B) heart, (C) muscle and (D) central nervous system (hippocampus + cortex). For each tissue, a differential expression signature was constructed corresponding to the effects of CR, and another signature was constructed corresponding to the effects of aging. Both signatures were based upon 3 or more experiments (see Figure 8 legend). CR and aging signatures were cross-tabulated, to place component genes into 9 separate categories, depending upon whether genes were increased by CR and/or aging (+), decreased by CR and/or aging (-), or whether CR and/or aging had no significant effect on gene expression (o). For each category, bars represent the adjusted Pearson residual (see Methods) (94). The absolute value of this quantity reflects the degree to which gene counts differ from what is expected based upon a random association between the CR and aging differential expression signatures. Positive residuals indicate that more genes belong to that category than expected by chance, given a random association between the effects of CR and aging. Negative residuals indicate that fewer genes belong to that category than expected by chance, given a random association between the effects of CR and aging. The adjusted Pearson residuals follow a standard normal distribution, with residuals larger than 3 in absolute value suggestive of significant, non-random associations between the effects of CR and aging [94]. The bars outlined in red indicate a significantly large or small residual (P < 0.05).