Figure 7.

Transcriptional deregulation of SIRT1 target genes occurs during normal aging. (A) Expression of SIRT1-associated gene from Figure 3 in the neocortex from young (5 months) and old (30 months) B6C3F₁ mice (n ≥ 6 per group), analyzed by q-PCR. Shown is the fold change in expression in old relative to young mice. P values are based on student’s one-tailed t-test. (B) Microarray expression analysis of SIRT1 target genes in the neocortex of young and old B6C3F₁ mice (n = 5 per group). SIRT1 target genes are significantly overrepresented amongst age-upregulated genes (χ² = 7.28, P = 0.0055). (C) Immunofluorescence analysis of SIRT1 and NeuN expression in the neocortex of NeSTO mice and Nestin-cre littermate controls. (D) q-RT-PCR analysis of SIRT1-bound genes from (A) and non-SIRT1-bound genes including housekeeping genes (rps16, hprt) and genes upregulated in 30 months old mice by microarray. NeSTO mice and Nestin-cre littermate controls (Control) were analyzed at 8–10 months (young, n = 3–5 and 6, respectively) or 18–19 months of age (old, n = 4 and 5, respectively). P values are based on student’s one-tailed t-test. Data are represented as mean +/− SEM.