Table 4.
Regulatory pathways for longevity‐associated proteins. Tier 1 proteins associated with longevity appear in boldface, tier 2 proteins appear with neither boldface nor parentheses, and proteins that we did not find significant for longevity but that were linked to the upstream regulators in the IPA knowledge base appear in parentheses. UniProt names and identifiers corresponding to the gene names appearing in the table can be found in Supplemental Table S1
|
Upstream Regulator |
Activation z‐score |
Target proteins measured in cohort |
|---|---|---|
| Alpha catenin | 3.403 | C6A3, (IGF1), (IGF2), (IGFBP2), (IGFBP6), (IL6ST), (LUM), MMP2, S100A8, S100A9, (TIMP1), (VCAM1) |
| APOE | 2.280 | ACTB, ADIPOQ, (APOD), (APOE), CD44, CLU, ECM1, (GPX3), (HABP2), (HSP90B1), HSPA5, HSPG2, (IGF1), (IGFBP6), (LRP1), MMP2, S100A8, S100A9, (SERPINA3), (TIMP1), (VCAM1) |
| LRP1 | 2.213 | (C1R), (C1S), (LRP1), MMP2, (SERPINF1), (SERPING1) |
| AIRE | −2.000 | (AMBP), (IGF2), ITIH3, S100A9 |
| PRKCE | −2.000 | CRP, HSPA5, (IL6ST), (VCAM1) |
| SOX9 | −2.000 | (COMP), (KIT), PTGDS, (VNN1) |
| NOS2 | −2.058 | ADIPOQ, (AZGP1), CD14, CD44, CFD, (CP), (ITIH4), LGALS3BP, S100A8, (SERPINA3), (TIMP1) |
| Creb | −2.157 | ADIPOQ, CD14, CD5L, CSF1R, DBH, (IGF1), (KRT1), MCAM, MMP2, (PCOLCE), (PRG4) |
| CSF1 | −2.159 | (APOE), CD163, CSF1R, FCGR3A, (FN1), (HSP90B1), HSPA5, (IGF1), (IL6ST), (PTPRJ), THBS1, (VCAM1) |
| IL10 | −2.166 | (APCS), CD14, CD163, CD44, CSF1R, FCGR3A, (IL6ST), MMP2, S100A8, (SELL), (TIMP1), (VCAM1) |
| CHUK | −2.178 | CLU, (CP), ENPP2, (IGFBP6), MMP2, (NID1), (SOD3), (VCAM1) |
| GLI1 | −2.182 | CLU, (FUC2), (IGF1), (IGF2), (IGFBP6), MMP2, (PVR), S100A9 |
| Vegf | −2.194 | A2 M, (ANPEP), (APOM), CD44, (CRTAC1), ENPP2, (FN1), (IGFBP3), (IL6ST), LYVE1, MMP2, NRP1, (PVR), (TIMP1), (VCAM1), VWF |
| F3 | −2.195 | F2, LCP1, MMP2, (SERPINC1), (VCAM1) |
| CXCL12 | −2.209 | (C5), CD14, CD44, (FN1), (KIT), MMP2, THBS1, (TIMP1) |
| STAT | −2.219 | A2 M, (AGT), CRP, (IL6ST), (SERPINA3), (TIMP1) |
| HNF4A | −2.313 | (A1BG), (AGT), (AHSG), ALCAM, (AMBP), (ANPEP), (APCS), (LPA4), (APOC1), (APOC2), (APOC3), (APOE), APOH, (APOM), (C1S), (C2), (C4B), C6, (C8G), (CP), (CPB2), CRP, DNAJC14, (F11), (F12), (F13B), (F7), (F9), (FETUB), GPLD1, (GSN), (HPX), (HSP90B1), HSPA5, (IGF1), (IL1RAP), (IL6ST), ITIH3, (ITIH4), (KNG1), (LPA), MBL2, (MST1), (PEPD), (PLG), (PON1), PROZ, PTGDS, (PTPRG), S100A9, (SERPINA10), (SERPINA3), (SERPINA4), (SHBG), (TTR), VTN |
| CCL2 | −2.334 | ADIPOQ, (IGF1), MMP2, PTGDS, (TIMP1), (VCAM1) |
| IL1B | −2.337 | A2 M, (APCS), (APOC2), (APOE), B2 M, (C1R), CD14, CD44, (CFB), (CP), (CPB2), CRP, ENPP2, (FN1), HSPA5, HSPG2, (IGF1), (IGFALS), (IGFBP3), (IGFBP5), (IGFBP6), (IL1RAP), LCP1, MMP2, NRP1, PTGDS, RNASE1, S100A8, S100A9, (SELENOP), (SERPINA3), (SERPINF2), (SPARC), THBS1, (TIMP1), (VCAM1) |
| SREBF1 | −2.348 | ADIPOQ, (ALDOA), (APOC3), CD14, CFD, (CFI), (FN1), (GPX3), HSPA5, IGHM, PTGDS, (SELENOP), (SERPINA3) |
| CTNNB1 | −2.375 | ACTB, ADIPOQ, ALCAM, (AOC3), (APOD), C6, CD44, CFD, CLU, DBH, ECM1, ENPP2, (FN1), (IGF2), (IGFBP2), (IGFBP5), IGHM, (JCHAIN), (KIT), (KRT1), MMP2, NCAM1, (PTPRJ), (RBP4), S100A8, (SERPINA3), (TIMP1), (VCAM1) |
| IL1 | −2.395 | (APOC3), (APOE), (C2), (CFB), (CP), CRP, CSF1R, (FN1), (IGF1), (KIT), (LRP1), MMP2, (RBP4), S100A9, (SAA4), (SELL), (SHBG), (SPARC), (TIMP1), (VCAM1) |
| CEBPD | −2.408 | (AGT), (APOC3), CD14, CLU, (CPB2), CSF1R, (IGF1), (IGFBP5) |
| LDL | −2.429 | (APOE), (HSP90B1), HSPA5, (HYOU1), (IGF1), (IGFBP2), (IGFBP3), (LRP1), MMP2, S100A8, (VCAM1), (VNN1) |
| ANGPT2 | −2.464 | (C1R), (CFB), (FN1), HSPA5, MMP2, (PROS1), (SERPING1), (SOD3), THBS1, (VCAM1) |
| MYD88 | −2.550 | (APCS), CD14, CD44, HSPA5, (IGF1), (IGFBP5), MMP2, S100A8, (TIMP1), (VCAM1) |
| CEBPA | −2.601 | A2 M, ADIPOQ, (AGT), (ANPEP), (LPA4), (APOC3), (APOC4), CD14, CFD, (CPB2), CSF1R, (F9), GGH, HPR, HSPA5, (IGF1), (IGFBP3), NRP1, (RARRES2), S100A8, S100A9, (SERPINF1), THBS1, (VCL) |
| EGF | −2.629 | ALCAM, (ANPEP), CD44, CLU, (CPB2), CSF1R, (FN1), (IGF1), (IGF2), (IGFALS), (IGFBP2), (IGFBP3), (IGFBP5), MMP2, (MST1), NCAM1, NRP1, S100A9, (SERPINA3), (SPARC), THBS1, (TIMP1), (VCAM1), (VCL) |
| PRDM1 | −2.642 | (APOM), CD44, (CFH), CRP, ECM1, (F5), (F9), IGHM, (JCHAIN), S100A8, S100A9, (SELL), (SERPINA3), (TTR) |
| IL5 | −2.763 | A2 M, (ALDOA), (HSP90B1), HSPA5, IGHM, (JCHAIN), (LUM), QSOX1 |
| cytokine | −2.763 | CLU, CRP, (IGFBP2), MMP2, (PON1), (SPARC), (TIMP1), (VCAM1), VWF |
| IL17A | −2.937 | ACTB, CD14, CD163, CRP, MMP2, NRP1, S100A8, S100A9, (SERPIND1), (TIMP1), (VCAM1), VWF |
| IL1A | −2.987 | (APOD), CD44, HSPG2, (IGF1), (IGFBP5), (KIT), MCAM, MMP2, S100A8, S100A9, (SERPINA3), (SPARC), (VCAM1) |
| IL6 | −3.053 | A2 M, (ADAMTS13), (AGT), (ANPEP), (APCS), (APOE), CD14, CD163, CD44, CFD, (CFH), (CFP), CLU, (COMP), (CP), (CPB2), CRP, CST3, ENPP2, (F12), (FN1), (GP1BA), (GP5), (HPX), HSPA5, (IGF1), (IGF2), (IGFBP3), (IGFBP5), (IGFBP6), IGHM, (IL6ST), (JCHAIN), (KIT), LCAT, (LPA), LRG1, MMP2, (PLG), (PON1), (PPBP), S100A9, (SAA4), (SERPINA3), (SERPINA7), THBS1, (TIMP1), (TTR), (VCAM1) |
| ADCYAP1 | −3.162 | (ATRN), (CRTAC1), ENPP2, (LUM), (MAN1A1), MCAM, (SERPINA3), (SERPINF1), (SPARC), (TGFBI) |