Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination
Figure 5.Increased mitochondrial activity among young vaccine responders. QuSage  was used to quantify activity of the KEGG oxidative phosphorylation pathway for young responders (open symbols) and older non-responders (filled symbols). +R indicates responder status and –R non-responder status. Results are shown for (A) the 2011-12 cohort and (B) the independent 2010-11 cohort. FDR values for (A) are provided in Supplementary Table 4B. For the 2010-11 cohort (B), statistically significant p values in young responders were at day 2 (p = 1.1e-05), day 7 (p = 2.3e-11), and day 28 (p = 2.4e-09) post-vaccine. For older non-responders significant p values were at day 2 (p=0.005) and day 28 (p = 2.1e-05) post-vaccine; the p value at day 7 was not significant (p > 0.05). (C) Over-representation (−log10(p-value)) of NRF1 (dashed lines), NRF2 (dash-dot lines) and E2F1 (solid lines) target genes calculated by the hypergeometric test in responders (open symbols) and non-responders (filled symbols) across time (x-axis). Target gene sets for NRF1, NRF2 and E2F1 were defined by the presence of promoter-region binding sites defined by V$NRF1_Q6, V$NRF2_Q4 and V$E2F1_Q4_01 TRANSFAC matrices, respectively. Significant p values were found for E2F1 in young responders at day 7 (FDR = 0.03) and day 28 (FDR = 1.76e-07) post-vaccine; for NRF1 in young responders at day 7 (FDR = 0.001) and day 28 (FDR = 2.3e-07) post-vaccine and in young non-responders at day 7 (FDR = 0.007) post-vaccine; and for NRF2 in young responders at day 28 (FDR = 0.03) post-vaccine. All remaining p values did not achieve statistical significance.