Figure 1
Figure 2
Figure 3
Lists of in common genes from significant CU-DREAM results comparing downregulation in resistance exercise and downregulation in aging
| In common | 3 (n= 8) | 2 (n= 165) |
|---|---|---|
| Genes | ATP5C1, CHCHD3, CYCS, DCUN1D5, DLAT, FAM171A1, NEDD1, RXRG | ACAA2, ACADM, ACADSB, AGPAT1, AIMP1, AIMP2, ANGEL2, ANKH, ASB12, ASPH, ATP2C1, ATP5F1, ATPAF1, BHLHE41, BLMH, BPGM, C11orf74, C14orf142, C16orf72, C21orf33, C6orf136, CALU, CCM2, CD36, CENPV, CHCHD4, CISD1, CMC1, COQ3, COX10, CRADD, CSPP1, CWC27, CYC1, DEXI, DNM1L, DPH2, DPH5, DTNA, DUS4L, DUSP3, DZIP3, EPM2A, ETV6, FAM100B, FAM110B, FAM190B, FAM82B, FBXO3, FH, FKBP1A, FRMD3, FSD2, FZD7, GBAS, GFM1, GFM2, GNPTAB, GOLGA2, GOLGA4, GOSR2, GOT1, GOT2, GRSF1, GTPBP8, HIBADH, HOOK2, HSPA4, IFRD2, ISCA1, KBTBD2, KCTD9, KPNA6, LANCL1, LPIN1, LYPLA1, LYRM5, MAP2K6, MAPKAP1, MFF, MKKS, MLEC, MOCS2, MRPL35, MRPL48, MRPS30, MRS2, MSRB2, MTRF1L, MTX2, MYOZ3, MYPOP, NAMPT, NDUFAF2, NDUFAF4, NEURL2, NMNAT1, NNT, NUDT6, OSBPL3, OXSM, PDHA1, PDSS1, PEX2, PGK1, PIAS2, PPARGC1A, PPIF, PPP2R3C, PRDX3, PRKAR2A, PSME4, PTCD3, PTPLA, PYROXD1, RABEP1, RABGGTB, RAVER2, RCHY1, RGS3, RNF144A, RPS6KC1, RWDD1, S100A1, SCYL2, SDHC, SDHD, SHISA4, SIRT5, SLC25A15, SLC25A4, SLC25A44, SLC25A46, SMAP1, SNTB1, SOBP, SRF, STAMBP, STRADB, SUCLA2, SYNGR1, TATDN1, TBC1D14, TEF, TFRC, TMTC4, TOMM40L, TOR3A, TPI1, TTN, TUBA3C, UBE2V1, UBP1, UCHL3, ULK2, UQCRB, UQCRH, USP38, UXS1, VLDLR, WIPI1, WSB2, WWP1, ZC3H8, ZNF438 |
Demographic data for the exercise and aging groups
| Exercise group GSE Type | 8479 Experimental results were measured before and after training from the same individuals for a specific duration. | 9103 Experimental results were measured from 2 defined sample groups (active/inactive). | 16907 Experimental results were measured before and after training from the same individuals for a specific duration. | 20319 Experimental results were measured from 2 defined sample groups (active/inactive). | Aging group GSE | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Duration of exercise | 6 months | 4 years | 12 months | 32 years | 80 | 1428 | 8479 | 9103 | 38718 | |
| Experimental group Experimental groups are the active or after-training groups in exercise GSEs and are the old age groups in the aging GSEs. | Samples (n) | 14 | 20 | 8 | 10 | 19 | 12 | 25 | 10 | 8 |
| Age (y) | 69.6 + 9.4 | 19-76 | 50–57 | 50–74 | 68.6 ± 8.4 | 70–80 | 70.5±13.5 | 65.1 ± 7.3 | 65-76 | |
| Control group Control groups are the sedentary or before-training groups in exercise GSEs and are the young age groups in the aging GSEs. | Samples (n) | 25 | 20 | 8 | 10 | 16 | 10 | 26 | 10 | 14 |
| Age (y) | 70.5+13.5 | 18–72 | 50–57 | 50–74 | 24.5 ± 6.5 | 19-25 | 21.2 ± 6.8 | 22.9 ± 4.1 | 19-28 | |
| Sex | Mixed | Mixed | Female | Mixed | Male | Male | Mixed | Mixed | Mixed | |
| Muscle biopsy | Vastus | Vastus | Vastus | Vastus | Vastus | Vastus | Vastus | Vastus | Biceps | |
| lateralis | lateralis | lateralis | lateralis | lateralis | lateralis | lateralis | lateralis | brachii | ||
| Extracted molecule | Total RNA | Total RNA | Total RNA | Total RNA | Total RNA | Total RNA | Total RNA | Total RNA | Total RNA | |
| Organization name | Buck Institute for Research on Aging USA | Mayo Clinic and Foundation USA | University of Jyväskylä Finland | University of Jyväskylä Finland | University of Rochester USA | Boston University USA | Buck Institute for Research on Aging USA | Mayo Clinic and Foundation USA | University of Michigan USA | |
CU-DREAM comparing upregulation in exercise and downregulation in aging
| Aging group | Exercise group | 8479 | 9103 | 16907 | 20319 |
|---|---|---|---|---|---|
| GSEs | GSEs (types) | (Resistance) | (Endurance) | (Power training) | (Physically active) |
| 80 | P | 6.73 × 10–2 | 3.78 × 10–4 | 6.58 × 10–1 | 1.32 × 10–1 |
| OR | 0.40 | 2.91 | 0 | 4.14 | |
| 95% CI | 0.15–1.10 | 1.57–5.38 | – | 0.56–30.80 | |
| 1428 | P | 5.29 × 10–1 | 9.73 × 10–15 | 3.54 × 10–2 | 8.29 × 10–1 |
| OR | 0.93 | 2.30 | 2.65 | 0.86 | |
| 95% CI | 0.73–1.17 | 1.85–2.85 | 1.03–6.79 | 0.21–3.54 | |
| 8479 | P | 5.07 × 10–24 | 1.34 × 10–22 | 1.20 × 10–1 | 8.31 × 10–2 |
| OR | 0.16 | 2.65 | 0 | 2.22 | |
| 95% CI | 0.11–0.24 | 2.16–3.24 | – | 0.88–5.60 | |
| 9103 | P | 4.13 × 10–2 | 2.76 × 10–12 | 5.90 × 10–1 | 5.97 × 10–1 |
| OR | 0.60 | 3.17 | 0.58 | 1.70 | |
| 95% CI | 0.36–0.99 | 2.26–4.47 | 0.08–4.20 | 0.23–12.36 | |
| 38718 | P | 2.85 × 10–18 | 2.35 × 10–9 | 4.65 × 10–1 | 6.82 × 10–2 |
| OR | 0.47 | 1.58 | 0.68 | 1.88 | |
| 95% CI | 0.40–0.56 | 1.36–1.83 | 0.25–1.90 | 0.94–3.74 |
CU-DREAM comparing downregulation in exercise and upregulation in aging
| Aging Group | Exercise group | 8479 | 9103 | 16907 | 20319 |
|---|---|---|---|---|---|
| GSEs | GSEs (types) | (Resistance) | (Endurance) | (Power Training) | (Physically active) |
| 80 | P | 1.81 × 10–3 | 1.25 × 10–2 | 7.93 × 10–1 | 6.39 × 10–1 |
| OR | 2.55 | 2.56 | 0.00 | 0.00 | |
| 95% CI | 1.39–4.68 | 1.19–5.48 | – | – | |
| 1428 | P | 9.35 × 10–1 | 3.03 × 10–1 | 9.34 × 10–1 | 8.91 × 10–1 |
| OR | 0.93 | 2.93 | 0.00 | 0.00 | |
| 95% CI | 0.16–5.56 | 0.34–25.15 | – | – | |
| 8479 | P | 1.81 × 10–103 | 7.43 × 10–2 | 9.05 × 10–1 | 7.52 × 10–1 |
| OR | 5.65 | 1.30 | 0.89 | 0.80 | |
| 95% CI | 4.74–6.73 | 0.97–1.74 | 0.12- 6.53 | 0.19–3.27 | |
| 9103 | P | 9.14 × 10–-61 | 3.04 × 10–51 | 3.98 × 10–1 | 9.03 × 10–1 |
| OR | 4.08 | 4.44 | 1.43 | 0.92 | |
| 95% CI | 3.41–4.89 | 3.59–5.48 | 0.62-3.26 | 0.22–3.76 | |
| 38718 | P | 9.22 × 10–9 | 8.59 × 10–13 | 2.32 × 10–1 | 3.09 × 10–1 |
| OR | 1.50 | 2.14 | 0.00 | 1.60 | |
| 95% CI | 1.31–1.72 | 1.73–2.64 | – | 0.64–4.01 |
DAVID/KEGG pathway results for endurance exercise_
| Significant molecular pathways | Q range | No. of GSEs in common | No. of genes | Lists of genes associated with the pathways |
|---|---|---|---|---|
| Oxidative phosphorylation | 8.8 × 10–44 –1.6 × 10–2 | 5/5 | 43 | ATP5B, ATP5C1, ATP5E, ATP5F1, ATP5G1, ATP5G3, ATP5H, ATP5J, ATP5L, ATP5O, COX4I1, COX5A, COX5B, COX6B1, COX6C, COX7B, COX7C, COX8A, CYC1, NDUFA10, NDUFA4, NDUFA6, NDUFA8, NDUFA9, NDUFAB1, NDUFB1, NDUFB10, NDUFB2, NDUFB8, NDUFB9, NDUFC1, NDUFS1, NDUFS2, NDUFS3, NDUFS8, SDHA, SDHB, UQCR11, UQCRB, UQCRC1, UQCRC2, UQCRFS1, UQCRQ |
| Cardiac muscle contraction | 3.8 × 10–10 –2.6 × 10–5 | 3/5 | 14 | COX4I1, COX5A, COX5B, COX6B1, COX6C, COX7B, COX7C, COX8A, CYC1, UQCRB, UQCRC1, UQCRC2, UQCRFS1, UQCRQ |
| Citrate cycle (TCA cycle) Significant in GSE 8479. | 3.6 × 10–5 | 1/5 | 7 | SDHA, SDHB, SUCLG1, CS, PDHA1, FH, MDH1 |
| Propanoate metabolism Significant in GSE 8479. | 8.3 × 10–3 | 1/5 | 5 | LDHB, ALDH7A1, ALDH1B1, SUCLG1, PCCB |
| Pyruvate metabolism Significant in GSE 8479. | 1.7 × 10–2 | 1/5 | 5 | LDHB, ALDH7A1, ALDH1B1, PDHA1, MDH1 |
| Arginine and proline metabolism Significant in GSE 8479. | 4.1 × 10–2 | 1/5 | 5 | GOT2, ALDH7A1, GOT1, ALDH1B1, CKMT2 |
Lists of in common genes from significant CU-DREAM results comparing downregulation in resistance exercise and upregulation in aging
| In common | 4 (n= 1) | 3 (n= 12) | 2 (n= 134 |
|---|---|---|---|
| Genes | CRIM1 | FEZ2, H3F3B, HNRNPM, LAMP1, METTL7A, NKTR, RBM5, SRRM2, TRMT112, TSC22D1, XRCC6, ZFHX3 | ADAMTS5, ALDH2, ALDH9A1, APBB3, ARFGAP2, ARL6IP5, ATG12, ATP1B4, ATP6V0A1, BCL6, BTG2, C1orf123, C21orf7, CALM1, CBLB, CEBPB, CELF2, CEP350, CFLAR, CLK4, COL4A3BP, CREB1, CREBBP, CXXC1, DDIT4, DHRS7, DMD, DPF2, DYNC1LI2, EFHD1, EIF1AD, ERRFI1, FAM107A, FAM8A1, FBLN1, FIGF, FILIP1, FKBP5, FOXN3, FOXO3, GGNBP2, GLG1, GLUL, GNPDA1, H1FX, HAUS2, HNRNPA1, HNRNPC, HSD17B7, HSF2, IGFBP6, IK, ING5, JDP2, KARS, KHDRBS1, KIAA0494, KLF10, KLF5, KLF9, KLHL28, LAMA2, LGR5, MBNL1, MCM7, MORC2, MYC, MYH11, NFAT5, NPHP3, NT5C2, PAM, PCM1, PDLIM5, PERP, PEX16, PHIP, PPDPF, PRDM2, PRDX6, PRKRIP1, PRNP, PTGES3, RASEF, RHEB, RNF103, RPL10A, RPL12, RPL13, RPL22, RPL23A, RPL4, RPL41, RPL7A, RPS4X, RPS6KA5, RRAD, RUNX1T1, SELM, SH3GLB1, SKAP2, SLBP, SLC7A6, SLIT2, SLPI, SMAD2, SOD3, STAG2, SUV420H1, SYNPO2, TANC1, TGFBR3, THUMPD1, TM2D3, TMEM43, TOP1, TP63, TPM3, TSR1, UACA, UBE2L3, UPF3A, USP54, VIT, WTAP, XPC, XPNPEP3, XRCC2, ZBTB16, ZMAT3, ZNF451, ZNF549, ZNF627, ZNF652 |
CU-DREAM comparing downregulation in exercise and downregulation in aging
| Aging group | Exercise group | 8479 | 9103 | 16907 | 20319 |
|---|---|---|---|---|---|
| GSEs | GSEs (types) | (Resistance) | (Endurance) | (Power Training) | (Physically active) |
| 80 | P | 1.47 × 10–1 | 4.72 × 10–1 | 7.60 × 10–1 | 5.84 × 10–1 |
| OR | 1.44 | 1.36 | 0.00 | 0.00 | |
| 95% CI | 0.88–2.38 | 0.58–3.17 | – | – | |
| 1428 | P | 1.81 × 10–1 | 9.97 × 10–1 | 3.44 × 10–1 | 8.72 × 10–1 |
| OR | 0.89 | 1.00 | 0.00 | 1.10 | |
| 95% CI | 0.76–1.05 | 0.73–1.37 | – | 0.34–3.54 | |
| 8479 | P | 1.24 × 10–67 | 9.92 × 10–1 | 8.39 × 10–1 | 9.69 × 10–2 |
| OR | 3.63 | 1.00 | 0.81 | 0.00 | |
| 95% CI | 3.11–4.24 | 0.73–1.37 | 0.11–6.00 | – | |
| 9103 | P | 1.72 × 10–5 | 9.47 × 10–1 | 1.11 × 10–1 | 4.09 × 10–1 |
| OR | 1.93 | 1.02 | 2.48 | 0.00 | |
| 95% CI | 1.42–2.61 | 0.55–1.88 | 0.78–7.89 | – | |
| 38718 | P | 5.21 × 10–54 | 2.10 × 10–7 | 2.50 × 10–1 | 8.04 × 10–1 |
| OR | 2.17 | 1.59 | 0.33 | 0.90 | |
| 95% CI | 1.97–2.40 | 1.33–1.90 | 0.04–2.43 | 0.39–2.09 |
Lists of in common genes from significant CU-DREAM results comparing upregulation in endurance exercise and downregulation in aging
| In common | 5 (n= 2) | 4 (n= 6) | 3 (n= 23) | 2 (n= 66) |
|---|---|---|---|---|
| Genes | ATP5C1 CYCS | ATP5G3, ATP5J, COX7B, CYC1, GSTK1, UQCRB | BHLHE41, C14orf2, CKMT2, COQ3, COX4I1, COX7C, EIF3K, GOT2, MRPS12, NDUFA4, NDUFB1, NDUFB2, NDUFB8, NEDD1, PDE4A, PPIF, PRDX2, SIRT5, SLC16A1, SLC38A1, ST8SIA5, TPI1, UQCRFS1 | ACSL6, ALDH1B1, ALDH7A1, ATP5E, ATP5F1, ATP5G1, ATP5L, ATP5O, BCAP29, BOLA3, C1orf151, C21orf33, C2orf88, CALU, CHCHD10, COX5A, COX5B, CS, DECR1, DPH5, DTNA, DUS4L, FAM162A, FH, FLJ11292, FRMD3, FYN, GNPTAB, GOSR2, GOT1, GPCPD1, GULP1, MIPEP, MRPL15, MRPL35, MRPL41, NDUFA6, NDUFA9, NDUFAB1, NDUFC1, NDUFS3, NDUFS8, NUDT6, OXNAD1, OXSM, PARVB, PDHA1, PHC3, POU6F1, PTCD3, PTPRO, RUNX2, SH3KBP1, SLC25A11, SLC25A4, ST6GALNAC2, SUCLG1, TMEM164, TNFAIP2, TOR3A, TUB, UQCRC1, UQCRC2, UQCRQ, WDR45, ZNF252 |
Molecular functions and phenotypes of genes significant in endurance exercise from the Kyoto Encyclopedia of Genes and Genomes oxidative phosphorylation pathway
| Gene | Number of GSEs in common | P range | Molecular function | Molecular and cellular phenotypes |
|---|---|---|---|---|
| ATP5C1 | 5/5 | 6.80 × 10–5 to 8.86 × 10–3 | ATP synthase γ-subunit | Catalyzes AT P synthesis, mainly expressed in the heart |
| ATP5G3 | 4/5 | 4.12 × 10–7 to 2.06 × 10–3 | ATP synthase lipid-binding Catalyzes ATP synthesis protein | |
| ATP5J | 4/5 | 6.58 × 10–5 to 3.57 × 10–3 | ATP synthase-coupling factor | Catalyzes AT P synthesis |
| COX7B | 4/5 | 8.81 × 10–5 to 6.36 × 10–3 | Cytochrome C oxidase subunit | Terminal oxidase in the mitochondrial electron transport |
| Accepts electrons from the Rieske | ||||
| CYC1 | 4/5 | 1.34 × 10–5 to 6.77 × 10–3 | Cytochrome C | protein and transfers electrons to cytochrome c in the mitochondrial |
| respiratory chain | ||||
| UQCRB | 4/5 | 9.80 × 10–6 to 4.15 × 10–3 | Ubiquinol-Cytochrome C reductase complex subunit | Redox-linked proton pumping |
| COX4I1 | 3/5 | 1.69 × 10–4 to 9.69 × 10–4 | Cytochrome C oxidase subunit | Catalyzes the electron transfer from reduced cytochrome c to oxygen |
| COX7C | 3/5 | 2.20 × 10–4 to 9.60 × 10–3 | Cytochrome C oxidase subunit | Catalyzes the electron transfer from reduced cytochrome c to oxygen |
| NDUFA 4 | 3/5 | 7.89 × 10–4 to 8.57 × 10–3 | α-Subcomplex subunit | Transfer of electrons from NADH to the respiratory chain |
| NDUFB1 | 3/5 | 4.95 × 10–5 to 5.58 × 10–3 | β-Subcomplex subunit | Transfer of electrons from NADH to the respiratory chain |
| NDUFB2 | 3/5 | 4.35 × 10–3 to 6.58 × 10–3 | β-Subcomplex Subunit | Transfer of electrons from NADH to the respiratory chain |
| NDUFB8 | 3/5 | 4.03 × 10–7 to 4.14 × 10–3 | β-Subcomplex Subunit | Transfer of electrons from NADH to the respiratory chain |
| UQCRFS1 | 3/5 | 6.28 × 10–6 to 2.61 × 10–3 | Ubiquinol-Cytochrome C reductase complex subunit | Generates an electrochemical potential coupled to ATP synthesis |
Molecular functions and phenotypes of significant remaining genes in endurance exercise
| Gene | Number of GSEs in common | P range | Molecular function | Molecular and cellular phenotypes |
|---|---|---|---|---|
| CYCS | 5/5 | 6.96 × 10–5 to 4.85 × 10–3 | Cytochrome C | Electron carrier protein, important apoptotic role |
| GSTK1 | 4/5 | 3.22 × 10–5 to 7.78 × 10–3 | Glutathione S-transferase subunit | Cellular detoxification |
| BHLHE41 | 3/5 | 1.34 × 10–6 to 9.60 × 10–3 | Helix-loop-helix protein | Transcriptional repressor |
| C14orf2 | 3/5 | 7.06 × 10–5 to 4.83 × 10–3 | Mitochondrial proteolipid | Chromosome 14 open reading frame Reversibly catalyzes the transfer of |
| CKMT2 | 3/5 | 7.66 × 10–9 to 5.91 × 10–3 | Mitochondrial creatine kinase | phosphate between ATP and phosphagens |
| COQ3 | 3/5 | 7.39 × 10–5 to 7.27 × 10–3 | COQ3 methyltransferase | Coenzyme Q biosynthesis Prevents premature joining of the 40S |
| EIF3K | 3/5 | 1.34 × 10–4 to 5.21 × 10–3 | Translation initiation factor | and 60S ribosomal subunits prior to initiation |
| GOT2 | 3/5 | 5.26 × 10–6 to 6.07 × 10–3 | Fatty acid-binding protein | Amino acid metabolism, facilitates cellular uptake of long-chain free fatty acids Key component of the small ribosomal subunit |
| MRPS12 | 3/5 | 5.51 × 10–4 to 3.48 × 10–3 | Mitochondrial ribosomal protein | |
| NEDD1 | 3/5 | 2.64 × 10–4 to 3.45 × 10–3 | Neural precursor cell protein | Mitosis progression, promotes the nucleation of microtubules from the spindle |
| PDE4A | 3/5 | 2.16 × 10–4 to 2.53 × 10–3 | Phosphodiesterase isozyme | Regulating the cellular concentration of cAMP |
| PPIF | 3/5 | 3.69 × 10–5 to 6.88 × 10–3 | Mitochondrial cyclophilin | Antiapoptotic activity |
| PRDX2 | 3/5 | 4.61 × 10–4 to 9.86 × 10–3 | Thiol-specific antioxidant | Eliminating peroxides generated during metabolism |
| SIRT5 | 3/5 | 2.03 × 10–4 to 4.98 × 10–3 | Regulatory protein | Regulation of transcription and apoptosis |
| SLC16A1 | 3/5 | 6.38 × 10–5 to 9.09 × 10–3 | Solute carrier | Catalyzes the movement of monocarboxylates across the plasma membrane |
| SLC38A1 | 3/5 | 3.49 × 10–5 to 9.75 × 10–4 | Solute carrier | Mediates cotransport of glutamine and sodium ions |
| ST8SIA5 | 3/5 | 1.04 × 10–5 to 1.97 × 10–3 | Sialyltransferase | Synthesis of gangliosides |
| TPI1 | 3/5 | 3.33 × 10–5 to 9.54 × 10–3 | Triosephosphate isomerase | Catalyzes the isomerization of G3P and DHAP in glycolysis and gluconeogenesis |