Pathway transcriptomes responsive to age, diet and gender. (a) Left: the ubiquitin-proteasome protein degradation pathway. E1, E2 and E3 are ubiquitin activating, conjugating and ligating enzymes, respectively. Ub, ubiquitin; 19S and 20S are proteasome subunits. Middle: the Wnt β-catenin signaling pathways. Fzd, frizzled; LRP, lipoprotein-related protein; DKK1, dickkopf 1; Frat, frequently rearranged in advanced T-cell lymphomas-1; GSK3β, glycogen synthase kinase-3β; Nlk, nemo-like kinase; NF-AT, nuclear factor of activated T cells; TCF, T cell-specific transcription factor; Tab1, TGF-beta activated kinase-1 binding protein-1; Tak1, TGF-beta-activated kinase 1. Right: Werner (WRN) interacting proteins involved in DNA repair and telomere homeostasis. PARP-1, poly (ADP-ribose) polymerase 1; FEN-1, flap endonuclease 1; DNAPKcs, DNA-dependent protein kinase catalytic subunit; Ku, Ku p70/p80 antigen; MRN, MRE11-RAD50-NBS1 protein complex; BLM, Bloom syndrome; TRF1 and TRF2, telomere repeat-binding factors 1 and 2. (b) Frequency of UPS pathway gene sensitivity to age, gender and diet in the striatum (genes identified based on a threshold of perturbation probability ≥ 0.10). (c) The perturbation probability of Uchl1 gene and/or its combinations in different CNS regions during aging and in response to CR.