Table 5.

Pathways associated with genes oppositely affected by aging and CR

Pathways	P-value	Molecules
CA1
Hypoxia Signaling in the Cardiovascular System	0.027	NFKBIE (1.4, −1.2), UBE2L6 (1.7, −1.4)
CA3
p53 Signaling	0.001	PRKDC (1.4, −1.3), PIK3R2 (−3.1, 2.8), BAX (1.8, −1.4), CTNNB1 (1.3, −1.3)
RAR Activation	0.010	PRKACB (−3.4, 2.7), NSD1 (1.5, −1.4), RDH10 (−1.2, 1.2), RDH11 (1.3, −1.2), PIK3R2 (−3.1, 2.8)
Oxidative Phosphorylation	0.016	COX7B (−1.3, 1.4), ATP5E (1.2, −1.2), NDUFV3 (1.6, −1.3), NDUFA7 (−1.8, 1.9), UQCRQ (1.3, −1.3)
Glucocorticoid Receptor Signaling	0.020	PRKACB (−3.4, 2.7), HSP90AB1 (−15.7, 2.5), BAG1 (1.4, −1.3), TAF5L (1.2, −1.2), PIK3R2 (−3.1, 2.8), POLR2I (1.4, −1.3)
N-Glycan Biosynthesis	0.023	MAN2A2 (1.5, −1.5), DPM2 (1.2, 1.2)
Mitochondrial Dysfunction	0.044	COX7B (−1.3, 1.4), NDUFV3 (1.6, −1.3), NDUFA7 (−1.8, 1.9)
DG
p53 Signaling	0.002	PIK3R2 (−3.2, 3.9), BAX (1.9, −1.5), CTNNB1 (1.2, −1.3)
Glucocorticoid Receptor Signaling	0.010	PRKACB (−2.6, 2.9), HSP90AB1 (−10.7, 9.5), BAG1 (1.3, −1.2), POLR2J (1.3, −1.2), PIK3R2 (−3.2, 3.9)
Oxidative Phosphorylation	0.017	ATP7B (−2.1, 1.7), COX7B (1.3, −1.4), NDUFV3 (1.4, −1.3)
Nucleotide Excision Repair Pathway	0.024	XPC (−1.7, 2.5), POLR2J (1.3, −1.2)
Hippocampus
Oxidative Phosphorylation	0.004	ATP5E (1.2, −1.1), ATP6V1B2 (−1.1, 1.1), COX15 (1.5, −1.4), COX5B (1.2, −1.2), COX6C (−1.5, 1.9), COX7B (1.3, −1.3), FAM63B (−3.4, 2.7), IP6K2 (−1.2, 1.1), NDUFA1 (1.1, −1.1), NDUFA12 (1.1, −1.1), NDUFA7 (−2.0, 1.9), NDUFB10 (1.3, −1.1), NDUFB4 (1.1, −1.1), NDUFS5 (1.2, −1.1), NDUFV3 (1.5, −1.4), UQCRQ (1.3, −1.2)
FcgRIIB Signaling in B Lymphocytes	0.007	BTK (2.1, −1.8), FCGR2B (1.9, −1.6), MAPK8 (−1.1, 1.2), MRAS (1.3, − 1.3), PIK3CA (1.4, −1.4), PIK3R2 (−3.3, 2.4), SOS1 (−1.2, 1.3)
Antigen Presentation Pathway	0.010	B2M (1.3, −1.2), CANX (1.1, −1.1), HLA-DQA1 (4.2, −2.6), HLA-DRB1 (4.9, −3.1), TAP2 (4.7, −2.3)
Ubiquinone Biosynthesis	0.012	NDUFA1 (1.1, −1.1), NDUFA12 (1.1, −1.1), NDUFA7 (−2.0, 1.9), NDUFB10 (1.3, −1.1), NDUFB4 (1.1, −1.1), NDUFS5 (1.2, −1.1), NDUFV3 (1.5, −1.4), EDF1 (1.4, −1.1)
Mitochondrial Dysfunction	0.020	NDUFA1 (1.1, −1.1), NDUFA12 (1.1, −1.1), NDUFA7 (−2.0, 1.9), NDUFB10 (1.3, −1.1), NDUFB4 (1.1, −1.1), NDUFS5 (1.2, −1.1), NDUFV3 (1.5, −1.4), COX15 (1.5, −1.4), COX5B (1.2, −1.2), COX6C (−1.5, 1.9), COX7B (1.3, −1.3), MAPK8 (−1.1, 1.2), GPX7 (1.2, −1.2), PSEN1 (1.3, −1.3)
Dendritic Cell Maturation	0.022	B2M (1.3, −1.2), CANX (1.1, −1.1), FCGR2A (1.2, −1.2), FCGR2B (1.9, −1.6), HLA-DQA1 (4.2, −2.6), HLA-DRB1 (4.9, −3.1), IFNAR1 (1.5, − 1.3), IRF8 (1.6, −1.6), MAPK8 (−1.1, 1.2), PIK3CA (1.4, −1.4), PIK3R2 (−3.3, 2.4), STAT2 (1.6, −1.2), TREM2 (1.9, −1.5), TYROBP (2.3, −1.4)
Lipid Antigen Presentation by CD1	0.023	B2M (1.3, −1.2), PDIA3 (1.3, −1.2)
Pyrimidine Metabolism	0.034	APOBEC1 (1.6, −1.6), DTYMK (−2.1, 2.1), NME3 (−1.1, 1.1), NME4 (1.3, −1.4), NME6 (1.4, −1.4), POLD4 (1.4, −1.5), POLR2F (1.3, −1.2), POLR2J (1.3, −1.2), POLR3D (1.2, −1.2), POLR3F (−1.5, 1.6), POLR3H (1.2, −1.2), POLRMT (−1.3, 1.5), RPUSD4 (1.2, −1.2), TRUB2 (1.3, −1.2)
NRF2-mediated Oxidative Stress Response	0.047	ACTA1 (1.3, −1.2), DNAJC17 (1.3, −1.3), DNAJC4 (1.4, −1.1), EIF2AK3 (1.2, −1.2), ERP29 (1.3, −1.2), FTL (1.3, −1.1), GSTA1 (1.2, − 1.1), HMOX1 (1.4, −1.4), MAPK8 (−1.1, 1.2), MGST1 (1.3, −1.2), MRAS (1.3, −1.3), PIK3CA (1.4, −1.4), PIK3R2 (−3.3, 2.4), PPIB (1.2, − 1.1), SCARB1 (1.3, −1.2), SLC35A2 (1.4, −1.2)

The fold change values for aging followed by CR are indicated in the brackets. Some molecules are associated with multiple pathways.