Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Early Adult - Upregulated 0610031j06rik kidney predominant NCU-G1 491 ± 6 504 ± 14 503 ± 11 527 ± 13 534 ± 12 0.04747 Aadat aminoadipate aminotransferase (synonym Kat2) 180 ± 5 201 ± 12 223 ± 7 244 ± 14 275 ± 7 0.00000 Abca2 ATP-binding cassette, sub-family A (ABC1), member 2 958 ± 28 1052 ± 58 1086 ± 36 1071 ± 44 1141 ± 41 0.05371 Acadl acetyl-Coenzyme A dehydrogenase, long-chain 423 ± 7 456 ± 11 478 ± 14 486 ± 13 512 ± 11 0.00003 Adk adenosine 1828 ± 43 1920 ± 38 1922 ± 22 2048 ± 30 1949 ± 44 0.00797 Ak3 Adenylate kinase 3 1124 ± 44 1193 ± 25 1201 ± 17 1212 ± 12 1254 ± 26 0.02244 Aldh6a1 aldehyde dehydrogenase family 6, subfamily A1 795 ± 26 828 ± 31 848 ± 24 897 ± 20 871 ± 18 0.03095 Aldh9a1 aldehyde dehydrogenase family 9, subfamily A1 577 ± 8 620 ± 10 618 ± 10 665 ± 12 667 ± 11 0.00000 Anxa4 A4 332 ± 20 366 ± 14 379 ± 11 404 ± 10 425 ± 16 0.00058 Anxa5 1080 ± 26 1155 ± 27 1188 ± 23 1293 ± 11 1327 ± 22 0.00000 Anxa7 541 ± 12 592 ± 18 563 ± 13 602 ± 12 619 ± 10 0.00060 Aplp2 sperm (YWK-II) 2485 ± 37 2667 ± 49 2621 ± 46 2621 ± 48 2569 ± 33 0.03734 Ass arginosuccinate synthetase 175 ± 8 200 ± 8 193 ± 11 214 ± 7 208 ± 10 0.04981 Bet1l Blocked early in transport 1 homolog (S. cerevisiae) like 249 ± 5 265 ± 13 289 ± 7 267 ± 9 287 ± 8 0.01063 Bhlhb3 basic helix-loop-helix domain containing, class B3 1942 ± 138 2017 ± 132 2087 ± 102 2167 ± 89 2344 ± 50 0.05287 Bmp6 bone morphogenetic protein 6 281 ± 5 311 ± 9 315 ± 4 307 ± 11 331 ± 7 0.00109 C1galt1 core1 UDP-galactose:N-acetylgalactosamine-alpha-R beta 1,3-galactosyltransferase 96 ± 8 120 ± 9 115 ± 6 109 ± 5 119 ± 4 0.05493 C1qb complement component 1, q subcomponent, beta polypeptide 544 ± 25 645 ± 18 636 ± 16 695 ± 25 807 ± 25 0.00000 Cd44 CD44 antigen 140 ± 6 149 ± 6 154 ± 8 153 ± 9 172 ± 7 0.03628 Cd53 CD53 antigen 230 ± 14 268 ± 9 303 ± 15 311 ± 8 418 ± 21 0.00000 Cd59 CD59 antigen 1090 ± 45 1128 ± 31 1151 ± 24 1148 ± 22 1245 ± 27 0.00703 Cdh13 13 440 ± 21 478 ± 20 527 ± 18 504 ± 21 517 ± 16 0.01635 Cml3 camello-like 3 280 ± 20 412 ± 16 437 ± 17 473 ± 21 535 ± 21 0.00000 Cryab crystallin, alpha B 1134 ± 45 1258 ± 71 1276 ± 32 1347 ± 60 1408 ± 68 0.02430 Ctgf connective tissue growth factor 306 ± 12 332 ± 19 391 ± 25 372 ± 23 464 ± 25 0.00005 Ctsb cathepsin B 4827 ± 89 5203 ± 86 5094 ± 119 5338 ± 179 5593 ± 96 0.00035 Ctse cathepsin E 77 ± 6 93 ± 8 92 ± 9 95 ± 5 119 ± 7 0.00223 Ctsh cathepsin H 631 ± 18 718 ± 34 704 ± 27 728 ± 13 799 ± 26 0.00084 Cyp4f2 cytochrome P450, family 4, subfamily F, polypeptide 2 173 ± 6 180 ± 9 192 ± 5 188 ± 4 210 ± 6 0.00111 Dci dodecenoyl-coenzyme A delta isomerase 405 ± 15 439 ± 11 436 ± 10 461 ± 16 456 ± 13 0.04317 Dcir3 dendritic cell inhibitory receptor 3 27 ± 4 45 ± 5 41 ± 3 42 ± 4 56 ± 3 0.00019 Decr1 2,4-dienoyl CoA reductase 1, mitochondrial 412 ± 11 449 ± 19 483 ± 13 479 ± 15 514 ± 6 0.00004 Dek DEK oncogene (DNA binding) 1128 ± 20 1169 ± 25 1273 ± 33 1229 ± 28 1252 ± 33 0.00587

Page 1 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Dusp3 membrane protein, palmitoylated 3 (MAGUK p55 subfamily member 3) 3355 ± 85 3509 ± 94 3618 ± 89 3712 ± 126 4042 ± 105 0.00018 F11r junctional adhesion molecule 1 202 ± 10 231 ± 13 228 ± 11 247 ± 9 248 ± 9 0.01909 Fau Finkel-Biskis-Reilly murine sarcoma virusubiquitously expressed 9920 ± 269 10555 ± 205 10244 ± 215 10923 ± 226 11225 ± 337 0.01013 Fcgr3 Fc receptor, IgG, low affinity III 292 ± 12 341 ± 12 353 ± 10 360 ± 21 419 ± 26 0.00056 Fen1 Flap structure-specific endonuclease 1 182 ± 4 197 ± 8 213 ± 6 198 ± 4 215 ± 4 0.00048 Frap1 FK506 binding protein 12-rapamycin associated protein 1 566 ± 13 617 ± 10 593 ± 11 616 ± 15 605 ± 10 0.03474 Gjb1 gap junction membrane channel protein beta 1 131 ± 18 142 ± 9 154 ± 8 171 ± 12 172 ± 8 0.05192 Gnai2 guanine nucleotide binding protein, alpha inhibiting 2 646 ± 24 663 ± 20 711 ± 31 718 ± 17 734 ± 16 0.02184 Gnb1 guanine nucleotide binding protein, beta 1 3494 ± 56 3592 ± 115 3723 ± 80 3802 ± 80 3831 ± 79 0.02868 Gpx3 glutathione peroxidase 3 199 ± 10 237 ± 12 226 ± 11 228 ± 6 241 ± 8 0.04138 Grip2 glutamate receptor interacting protein 2 120 ± 8 127 ± 3 137 ± 7 140 ± 3 155 ± 5 0.00075 Gstp1 glutathione-S-transferase, pi 1 1978 ± 41 2075 ± 66 2267 ± 55 2192 ± 94 2574 ± 98 0.00002 Hapln2 Hyaluronan and proteoglycan link protein 2 579 ± 29 631 ± 31 617 ± 21 694 ± 39 707 ± 25 0.01427 Hexa hexosaminidase A 587 ± 17 624 ± 13 611 ± 11 645 ± 18 671 ± 17 0.00486 Idb4 inhibitor of DNA binding 4 332 ± 13 393 ± 18 391 ± 17 419 ± 12 445 ± 14 0.00006 isg12(a) putative ISG12(a) protein 4145 ± 74 4507 ± 158 4469 ± 147 4770 ± 70 4587 ± 124 0.02035 Itpr2 inositol 1,4,5-triphosphate receptor 2 108 ± 4 136 ± 9 131 ± 4 138 ± 10 139 ± 6 0.02742 Kcna3 potassium voltage-gated channel, shaker-related subfamily, member 3 49 ± 9 61 ± 7 69 ± 4 74 ± 4 63 ± 3 0.04482 Kcnj6 potassium inwardly-rectifying channel, subfamily J, member 6 65 ± 6 81 ± 9 85 ± 9 112 ± 7 90 ± 9 0.00650 Lamp1 lysosomal membrane glycoprotein 1 2639 ± 59 2722 ± 55 2741 ± 61 2839 ± 94 2918 ± 52 0.02548 Lgals1 lectin, galactose binding, soluble 1 231 ± 14 244 ± 11 272 ± 10 277 ± 10 295 ± 7 0.00016 Lgmn legumain 843 ± 34 903 ± 29 937 ± 32 926 ± 45 1059 ± 36 0.00106 LOC170927 Mid-1-related chloride channel 1 229 ± 7 246 ± 5 255 ± 12 244 ± 6 259 ± 5 0.04738 LOC171574 3 100 ± 6 128 ± 6 122 ± 4 124 ± 6 118 ± 7 0.03324 LOC246264 KRAB/zinc finger suppressor protein 1 (KS1) 24 ± 6 44 ± 7 48 ± 5 50 ± 5 41 ± 4 0.01327 LOC287708 similar to small GTPase 765 ± 48 898 ± 48 925 ± 43 997 ± 43 926 ± 59 0.04091 LOC292486 similar to 1500031O19Rik protein 1428 ± 34 1466 ± 30 1509 ± 13 1498 ± 36 1542 ± 20 0.04173 LOC296468 similar to livin inhibitor of isoform beta; livin inhibitor-of-apotosis; baculovira 112 ± 6 136 ± 8 132 ± 8 153 ± 8 174 ± 9 0.00002 LOC302999 similar to tripartite motif protein 32 134 ± 5 151 ± 9 151 ± 7 173 ± 11 173 ± 7 0.00497 LOC312670 Adiponectin receptor 2 586 ± 12 628 ± 20 646 ± 15 658 ± 22 709 ± 15 0.00010 LOC362938 similar to PDZ-domain protein scribble 331 ± 10 367 ± 15 350 ± 6 379 ± 9 370 ± 6 0.00875 Magi3 membrane-associated guanylate kinase-related (MAGI-3) 393 ± 14 446 ± 12 435 ± 13 429 ± 12 440 ± 9 0.02694 Maob monoamine oxidase B 1900 ± 69 2006 ± 47 2032 ± 52 2108 ± 76 2324 ± 50 0.00005 Mawbp MAWD binding protein 169 ± 16 216 ± 9 228 ± 12 240 ± 14 276 ± 14 0.00002

Page 2 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Mcl1 myeloid cell leukemia sequence 1 788 ± 26 869 ± 38 901 ± 30 911 ± 37 962 ± 33 0.01122 Mertk c-mer proto-oncogene tyrosine kinase 109 ± 5 136 ± 9 125 ± 7 127 ± 7 142 ± 8 0.03262 Mg87 Mg87 protein 812 ± 21 863 ± 19 884 ± 21 917 ± 34 955 ± 15 0.00039 MGC94010 similar to SPI6 207 ± 14 229 ± 16 249 ± 7 242 ± 4 269 ± 12 0.00620 MGC94579 upregulated in colorectal cancer 1 protein 1717 ± 18 1800 ± 30 1841 ± 20 1910 ± 34 1828 ± 31 0.00067 Myo1e IE 173 ± 7 183 ± 7 186 ± 9 199 ± 11 210 ± 4 0.00579 Ninj2 ninjurin 2 271 ± 9 284 ± 13 315 ± 9 318 ± 12 335 ± 14 0.00232 Npc2 Niemann Pick type C2 1884 ± 35 2179 ± 42 2281 ± 77 2445 ± 67 2978 ± 55 0.00000 Nqo1 NAD(P)H dehydrogenase, quinone 1 270 ± 11 312 ± 14 293 ± 8 306 ± 12 312 ± 8 0.04325 Nt5 5 nucleotidase 190 ± 10 212 ± 12 209 ± 10 220 ± 16 237 ± 7 0.04428 Pde8a Phosphodiesterase 8A 263 ± 11 284 ± 23 302 ± 6 312 ± 17 323 ± 12 0.05223 Pdk2 kinase, isoenzyme 2 1011 ± 31 1078 ± 30 1069 ± 41 1154 ± 41 1138 ± 32 0.04758 Phldb1 pleckstrin homology-like domain, family B, member 1 255 ± 23 335 ± 17 297 ± 10 321 ± 15 343 ± 19 0.00762 Pip5k2c phosphatidylinositol-4-phosphate 5-kinase, type II, gamma 723 ± 16 761 ± 9 768 ± 15 798 ± 18 771 ± 13 0.02002 Pkm2 pyruvate kinase, muscle 6254 ± 126 6900 ± 37 6727 ± 125 6909 ± 130 6556 ± 158 0.00631 Plekhb1 evectin-1 3955 ± 120 4172 ± 109 4272 ± 109 4456 ± 136 4590 ± 114 0.00286 Prkwnk1 protein kinase, lysine deficient 1 1565 ± 41 1643 ± 49 1764 ± 46 1725 ± 48 2009 ± 42 0.00000 Psmb9 proteosome (prosome, macropain) subunit, beta type 9 82 ± 5 95 ± 3 101 ± 3 119 ± 3 127 ± 6 0.00000 Ptpn11 protein tyrosine phosphatase, non-receptor type 11 3639 ± 79 3928 ± 89 4043 ± 55 4298 ± 134 4472 ± 111 0.00000 Qdpr quinoid dihydropteridine reductase 4582 ± 82 5298 ± 76 5589 ± 108 5811 ± 158 6059 ± 153 0.00000 Rab13 RAB13, member RAS oncogene family 239 ± 15 302 ± 16 273 ± 13 294 ± 12 299 ± 12 0.01060 Recc1 Replication factor C 374 ± 12 440 ± 12 418 ± 15 411 ± 10 435 ± 14 0.01336 Renbp renin binding protein 268 ± 17 313 ± 17 296 ± 8 316 ± 19 349 ± 16 0.01487 Rpl10 ribosomal protein L10 6669 ± 96 6932 ± 210 7006 ± 99 6888 ± 130 7272 ± 141 0.04704 Rpl15 ribosomal protein L15 5172 ± 92 5292 ± 48 5266 ± 34 5449 ± 90 5416 ± 68 0.05150 Rplp1 ribosomal protein, large, P1 12368 ± 189 12940 ± 234 12688 ± 140 13001 ± 127 13346 ± 280 0.02773 Rps12 ribosomal protein S12 6670 ± 104 6836 ± 92 7135 ± 170 7115 ± 157 7374 ± 119 0.00292 Rps14 ribosomal protein S14 8693 ± 154 9066 ± 86 9086 ± 127 9263 ± 162 9383 ± 185 0.02639 Rps15 ribosomal protein S15 5475 ± 170 5700 ± 127 5805 ± 60 6131 ± 90 5964 ± 128 0.01116 Rps20 ribosomal protein S20 4834 ± 76 5106 ± 134 5283 ± 117 5108 ± 165 5356 ± 78 0.02690 Rps3a ribosomal protein S3a 6968 ± 61 7201 ± 135 7430 ± 155 7570 ± 93 7833 ± 137 0.00012 Rps5 ribosomal protein S5 4055 ± 61 4211 ± 97 4229 ± 44 4288 ± 105 4421 ± 87 0.04424 Rps8 ribosomal protein S8 6578 ± 112 6805 ± 61 6977 ± 104 7232 ± 65 7341 ± 153 0.00025 S100a6 S100 calcium binding protein A6 (calcyclin) 138 ± 11 153 ± 9 173 ± 14 203 ± 14 231 ± 15 0.00002

Page 3 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA S100b , beta polypeptide 10957 ± 232 11656 ± 199 11640 ± 229 12241 ± 216 13085 ± 267 0.00000 Sgk serum/glucocorticoid regulated kinase 1433 ± 132 1616 ± 148 1903 ± 175 1684 ± 161 2215 ± 161 0.00851 Slc1a3 solute carrier family 1 (glial high affinity glutamate transporter), member 3 7040 ± 188 7316 ± 212 7371 ± 198 7743 ± 123 8093 ± 90 0.00018 Slc33a1 acetyl-CoA transporter 520 ± 15 554 ± 12 551 ± 10 572 ± 8 545 ± 8 0.02923 Slc9a3 solute carrier family 9, member 3 73 ± 4 84 ± 3 98 ± 8 98 ± 7 117 ± 6 0.00003 Slco1a4 solute carrier organic anion transporter family, member 1a4 1076 ± 26 1125 ± 25 1138 ± 30 1179 ± 21 1192 ± 32 0.04319 Slco2b1 solute carrier organic anion transporter family, member 2b1 340 ± 13 369 ± 15 384 ± 14 391 ± 13 438 ± 15 0.00023 Sod1 superoxide dismutase 1 4986 ± 77 5179 ± 79 5325 ± 103 5462 ± 101 5271 ± 119 0.04912 Sparcl1 SPARC-like 1 (mast9, hevin) 13144 ± 242 14120 ± 268 13757 ± 262 14333 ± 428 14561 ± 257 0.01308 Spata6 spermatogenesis associated 6 96 ± 4 116 ± 2 105 ± 5 108 ± 5 112 ± 3 0.01170 Spdy1 speedy homolog 1 (Drosophila) 114 ± 5 129 ± 7 132 ± 5 138 ± 10 146 ± 6 0.01808 Syne1 nesprin-1 1178 ± 15 1227 ± 26 1275 ± 30 1298 ± 28 1262 ± 35 0.05383 Wif1 Wnt inhibitory factor 1 66 ± 4 102 ± 11 91 ± 9 96 ± 9 104 ± 9 0.04747 Xdh xanthine dehydrogenase 136 ± 6 175 ± 9 158 ± 4 169 ± 4 186 ± 7 0.00007 Early Adult - Downregulated Agpat4 1-acylglycerol-3-phosphate O-acyltransferase 4 637 ± 20 604 ± 11 597 ± 15 582 ± 14 554 ± 18 0.01132 Arf1 ADP-ribosylation factor 1 3820 ± 93 3720 ± 91 3502 ± 92 3589 ± 103 3410 ± 43 0.00442 Atp1a3 ATPase, Na+/K+ transporting, alpha 3 polypeptide 3917 ± 85 3837 ± 84 3719 ± 68 3683 ± 91 3537 ± 55 0.00681 AZF1 zinc finger protein 1 1390 ± 23 1342 ± 29 1326 ± 38 1254 ± 44 1243 ± 37 0.02586 B3gat2 galactoside beta-1,3-glucuronyltransferase 394 ± 22 334 ± 11 361 ± 9 325 ± 16 297 ± 11 0.00017 Chn2 chimerin (chimaerin) 2 215 ± 12 162 ± 7 164 ± 6 186 ± 11 149 ± 7 0.00002 Clcn2 chloride channel 2 964 ± 22 868 ± 28 858 ± 40 885 ± 45 838 ± 22 0.05055 Cldn11 claudin 11 531 ± 29 474 ± 21 460 ± 21 428 ± 32 447 ± 17 0.05196 Col3a1 collagen, type III, alpha 1 109 ± 10 86 ± 6 81 ± 4 81 ± 7 90 ± 2 0.01691 Cox7b cytochrome c oxidase subunit VIIb 7171 ± 126 6954 ± 136 6801 ± 118 6916 ± 107 6512 ± 86 0.00201 Cyp51 cytochrome P450, subfamily 51 2016 ± 36 1801 ± 43 1850 ± 63 1780 ± 57 1707 ± 32 0.00056 Daf Decay accelarating factor 1 62 ± 4 39 ± 2 50 ± 3 44 ± 4 42 ± 3 0.00006 Dcamkl1 double cortin and calcium/-dependent protein kinase-like 1 3920 ± 38 3796 ± 59 3752 ± 44 3722 ± 55 3461 ± 58 0.00000 Dctn1 1 2444 ± 46 2290 ± 35 2332 ± 39 2305 ± 69 2231 ± 46 0.04170 Ddb1 damage-specific DNA binding protein 1 654 ± 33 568 ± 27 586 ± 35 508 ± 37 554 ± 28 0.04875 Dpysl3 dihydropyrimidinase-like 3 (Crmp4) 409 ± 3 355 ± 11 345 ± 4 338 ± 9 323 ± 7 0.00000 Egr2 early growth response 2 182 ± 24 140 ± 12 151 ± 9 141 ± 12 124 ± 6 0.03287 Eif4e eukaryotic translation initiation factor 4E 2320 ± 40 2123 ± 41 2198 ± 34 2180 ± 50 2149 ± 33 0.00747 Elovl6 ELOVL family member 6, elongation of long chain fatty acids (yeast) 498 ± 14 448 ± 13 448 ± 15 450 ± 16 436 ± 7 0.01330

Page 4 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Emd emerin 300 ± 6 294 ± 6 278 ± 10 275 ± 9 252 ± 8 0.00056 Epn2 Epsin 2 354 ± 14 346 ± 9 323 ± 10 334 ± 9 310 ± 11 0.03824 Erp70 protein disulfide isomerase related protein (calcium-binding protein, intestinal-related 430 ± 11 417 ± 13 385 ± 15 391 ± 17 371 ± 17 0.04980 F2r factor II () receptor 703 ± 18 616 ± 20 603 ± 21 574 ± 17 541 ± 21 0.00001 Fath fat tumor suppressor homolog (Drosophila) 626 ± 25 578 ± 17 598 ± 11 579 ± 14 553 ± 14 0.03626 Fbln2 2 549 ± 19 478 ± 22 459 ± 16 452 ± 17 419 ± 13 0.00003 Fkbp1b FK506 binding protein 1b 498 ± 10 471 ± 28 452 ± 24 437 ± 8 403 ± 12 0.00423 Fyn fyn proto-oncogene 666 ± 15 638 ± 10 641 ± 8 601 ± 15 609 ± 15 0.01002 Gamt guanidinoacetate methyltransferase 752 ± 19 693 ± 25 716 ± 9 690 ± 18 685 ± 12 0.05191 Glra2 glycine receptor, alpha 2 subunit 132 ± 11 102 ± 5 109 ± 7 87 ± 6 85 ± 6 0.00024 Hbld2 HesB protein 1147 ± 16 1060 ± 15 1062 ± 26 1042 ± 31 997 ± 24 0.00175 Hig1 Hypoxia induced gene 1 497 ± 12 450 ± 20 462 ± 16 440 ± 13 397 ± 19 0.00274 Hmox2 heme oxygenase (decycling) 2 819 ± 26 747 ± 18 758 ± 20 697 ± 23 690 ± 13 0.00015 Homer1 homer homolog 1 (Drosophila) 1038 ± 58 887 ± 63 695 ± 20 723 ± 24 634 ± 40 0.00000 Igf2 insulin-like growth factor 2 267 ± 25 234 ± 6 196 ± 3 198 ± 14 170 ± 9 0.00007 Igfbp2 insulin-like growth factor binding protein 2 353 ± 41 279 ± 23 282 ± 15 241 ± 16 273 ± 13 0.02785 Lmo3 LIM domain only 3 912 ± 23 890 ± 32 867 ± 17 844 ± 18 792 ± 15 0.00111 LOC293103 similar to RIKEN cDNA 0610007P06 1596 ± 19 1572 ± 31 1537 ± 34 1551 ± 37 1465 ± 34 0.03781 LOC293863 similar to Eso3 protein 1783 ± 40 1708 ± 32 1701 ± 23 1724 ± 37 1642 ± 27 0.03629 LOC294446 similar to Myristoylated alanine-rich C-kinase substrate (MARCKS) 232 ± 8 188 ± 14 197 ± 11 159 ± 8 187 ± 13 0.00698 LOC300276 similar to type IV collagen alpha 5 chain 249 ± 10 237 ± 9 210 ± 8 182 ± 8 171 ± 12 0.00000 LOC303746 similar to mitochondrial ribosomal protein L12 898 ± 25 837 ± 20 820 ± 15 820 ± 12 804 ± 12 0.00309 Lpl lipoprotein lipase 270 ± 15 218 ± 11 212 ± 17 202 ± 5 178 ± 8 0.00002 Maged1 melanoma antigen, family D, 1 3492 ± 69 3449 ± 69 3323 ± 69 3330 ± 74 3193 ± 53 0.01171 Mapk10 mitogen activated protein kinase 10 1243 ± 12 1129 ± 26 1154 ± 32 1161 ± 34 1137 ± 25 0.05494 MGC105793 similar to chromobox homolog 3; heterochromatin protein HP1 gamma; HP1 gamma 3175 ± 33 2953 ± 78 3037 ± 72 2971 ± 88 2889 ± 54 0.05132 MGC93924 similar to RIKEN cDNA 3110043O21 gene 624 ± 26 585 ± 17 561 ± 17 542 ± 16 548 ± 19 0.04114 MGC94233 similar to RIKEN cDNA 6720485C15 453 ± 9 417 ± 10 413 ± 19 405 ± 18 377 ± 14 0.01399 Mpzl1 myelin protein zero-like 1 465 ± 14 420 ± 18 407 ± 14 404 ± 9 398 ± 12 0.00799 Myr8 myosin heavy chain Myr 8 284 ± 13 241 ± 16 209 ± 11 219 ± 15 219 ± 12 0.00262 Nid nidogen (entactin) 109 ± 5 75 ± 5 76 ± 2 68 ± 6 70 ± 3 0.00000 NM9.2 ATPase, H+ transporting, V0 subunit 2685 ± 28 2593 ± 21 2622 ± 27 2536 ± 21 2547 ± 35 0.00644 Nmbr neuromedin B receptor 135 ± 6 127 ± 5 125 ± 5 115 ± 5 110 ± 5 0.01004 Npap60 associated protein 123 ± 3 101 ± 5 108 ± 7 105 ± 10 86 ± 6 0.00519

Page 5 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Nr4a2 nuclear receptor subfamily 4, group A, member 2 649 ± 31 592 ± 34 574 ± 23 551 ± 27 497 ± 21 0.00352 Odc1 ornithine decarboxylase 1 944 ± 57 843 ± 27 832 ± 26 854 ± 39 775 ± 20 0.01927 Pak3bp Rho guanine nucleotide exchange factor 7 367 ± 10 333 ± 9 329 ± 10 334 ± 15 327 ± 6 0.04751 Pcyox1 chloride ion pump-associated 55 kDa protein 246 ± 10 224 ± 14 226 ± 7 190 ± 13 205 ± 10 0.01390 Pfn1 1 3097 ± 65 3013 ± 71 2904 ± 59 2810 ± 92 2786 ± 50 0.00823 Pfn2 profilin 2 2545 ± 53 2416 ± 67 2436 ± 38 2310 ± 34 2187 ± 26 0.00000 Porf1 preoptic regulatory factor-1 235 ± 16 220 ± 10 198 ± 8 196 ± 5 189 ± 7 0.00723 Pou3f1 POU domain, class 3, transcription factor 1 958 ± 43 882 ± 54 812 ± 20 787 ± 21 768 ± 35 0.00441 Ppm1b protein phosphatase 1B, magnesium dependent, beta isoform 896 ± 27 819 ± 33 838 ± 29 780 ± 29 780 ± 20 0.01995 Ppp2r2c protein phosphatase 2 (formerly 2A), regulatory subunit B (PR 52), gamma isoform 211 ± 14 198 ± 10 170 ± 4 171 ± 7 158 ± 9 0.00145 Prkcb1 protein kinase C, beta 1 1689 ± 37 1601 ± 78 1550 ± 62 1459 ± 49 1414 ± 66 0.01949 Rab11a RAB11a, member RAS oncogene family 1586 ± 33 1474 ± 23 1487 ± 39 1463 ± 56 1401 ± 25 0.01424 Rab12 RAB12, member RAS oncogene family 360 ± 22 309 ± 22 334 ± 17 288 ± 19 282 ± 16 0.02986 Rasd1 RAS, dexamethasone-induced 1 734 ± 15 682 ± 20 654 ± 26 677 ± 26 633 ± 21 0.03724 Rasd2 RASD family, member 2 366 ± 12 331 ± 16 324 ± 4 330 ± 11 295 ± 12 0.00224 Robo1 roundabout homolog 1 (Drosophila) 201 ± 7 170 ± 7 184 ± 10 161 ± 11 174 ± 6 0.02493 Sec6l1 SEC6-like 1 (S. cerevisiae) 400 ± 13 369 ± 12 366 ± 13 366 ± 11 345 ± 8 0.02184 Serpini1 serine (or cysteine) peptidase inhibitor, clade I, member 1 2107 ± 43 1956 ± 49 1996 ± 44 1930 ± 51 1822 ± 51 0.00270 Slco1c1 solute carrier organic anion transporter family, member 1c1 1032 ± 31 966 ± 29 949 ± 20 916 ± 27 854 ± 29 0.00070 Snrpn small nuclear ribonucleoprotein N 5513 ± 147 5372 ± 78 5322 ± 74 5309 ± 72 5012 ± 64 0.00282 Stmn2 -like 2 6479 ± 271 6142 ± 249 5821 ± 233 5796 ± 227 5102 ± 206 0.00126 Stxbp5 syntaxin binding protein 5 (tomosyn) 292 ± 10 282 ± 7 265 ± 10 274 ± 3 259 ± 7 0.02279 Suclg1 succinate-CoA ligase, GDP-forming, alpha subunit 1788 ± 43 1633 ± 47 1659 ± 66 1592 ± 45 1603 ± 33 0.04549 Taz Tafazzin 312 ± 10 293 ± 12 281 ± 5 286 ± 10 261 ± 11 0.01250 Timm22 translocase of inner mitochondrial membrane 22 homolog (yeast) 249 ± 12 245 ± 11 228 ± 6 223 ± 5 219 ± 7 0.05479 Tpm3 3, gamma 439 ± 9 405 ± 11 416 ± 14 399 ± 11 385 ± 9 0.00842 Tpo1 developmentally regulated protein TPO1 464 ± 12 416 ± 17 417 ± 14 400 ± 11 381 ± 10 0.00049 Trpc4 transient receptor potential cation channel, subfamily C, member 4 339 ± 9 321 ± 17 299 ± 14 286 ± 11 285 ± 12 0.01896 Tsnax translin-associated factor X 1736 ± 42 1698 ± 56 1613 ± 27 1627 ± 30 1517 ± 37 0.00199 Tspan2 tetraspan 2 1527 ± 42 1365 ± 29 1370 ± 23 1337 ± 68 1329 ± 31 0.00893 Ttr transthyretin 3460 ± 1481 270 ± 40 232 ± 35 227 ± 41 438 ± 114 0.00285 Txnl2 thioredoxin-like 2 1721 ± 50 1609 ± 68 1670 ± 24 1557 ± 48 1520 ± 40 0.02723 Ugt8 UDP-glucuronosyltransferase 8 601 ± 21 523 ± 16 509 ± 23 499 ± 28 486 ± 13 0.00182 Usf1 upstream transcription factor 1 485 ± 18 465 ± 11 436 ± 9 438 ± 8 428 ± 6 0.00160

Page 6 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Vad vitamin A-deficient testicular protein 5 913 ± 25 865 ± 36 820 ± 24 838 ± 27 731 ± 23 0.00014 Vmp1 vacuole Membrane Protein 1 642 ± 21 576 ± 21 566 ± 27 497 ± 14 522 ± 25 0.00051 Vtn vitronectin 228 ± 14 185 ± 7 185 ± 9 178 ± 11 148 ± 5 0.00001 Wrnip1 Werner helicase interacting protein 1 700 ± 14 684 ± 20 660 ± 14 630 ± 18 636 ± 16 0.01873 Zdhhc2 zinc finger, DHHC domain containing 2 665 ± 15 616 ± 30 635 ± 11 597 ± 11 594 ± 15 0.04340 Intermediate - Upregulated 38597 septin 2 1557 ± 44 1555 ± 44 1579 ± 56 1655 ± 26 1691 ± 31 0.05219 ADRP adipose differentiation-related protein 166 ± 7 170 ± 6 178 ± 5 183 ± 9 195 ± 7 0.03114 Alad aminolevulinate, delta-, dehydratase 557 ± 12 554 ± 26 592 ± 5 622 ± 18 607 ± 19 0.03199 Apod apolipoprotein D 2394 ± 70 2440 ± 53 2684 ± 87 2911 ± 78 2770 ± 50 0.00001 Asah1 N-acylsphingosine amidohydrolase 1 297 ± 12 289 ± 12 319 ± 8 342 ± 15 335 ± 15 0.02193 Bcas1 breast carcinoma amplified sequence 1 3545 ± 132 3465 ± 79 3734 ± 185 3762 ± 153 4097 ± 154 0.02286 C3 complement component 3 261 ± 11 336 ± 18 374 ± 15 463 ± 23 652 ± 14 0.00000 Cdw92 CDW92 antigen 987 ± 24 1001 ± 32 1079 ± 33 1106 ± 85 1251 ± 36 0.00058 Cln2 ceroid-lipofuscinosis, neuronal 2 658 ± 25 659 ± 20 706 ± 17 707 ± 25 786 ± 24 0.00067 Cutl1 cut-like 1 (Drosophila) 355 ± 6 338 ± 19 388 ± 20 418 ± 26 426 ± 20 0.01015 Eno3 enolase 3, beta 34 ± 4 33 ± 2 39 ± 3 45 ± 5 48 ± 3 0.00631 Fah fumarylacetoacetate hydrolase 394 ± 17 397 ± 13 413 ± 12 473 ± 27 502 ± 16 0.00004 Fcgr2b Fc receptor, IgG, low affinity IIb 93 ± 5 113 ± 5 134 ± 6 142 ± 7 221 ± 12 0.00000 Fxyd3 FXYD domain-containing ion transport regulator 3 242 ± 7 244 ± 11 266 ± 5 277 ± 11 315 ± 15 0.00011 Giot2 gonadotropin inducible ovarian transcription factor 2 34 ± 2 34 ± 3 49 ± 8 52 ± 4 46 ± 3 0.01066 Gm2a GM2 activator protein 409 ± 22 390 ± 17 425 ± 22 479 ± 23 479 ± 9 0.00211 Gpx4 glutathione peroxidase 4 6296 ± 118 6359 ± 137 6467 ± 121 6644 ± 94 6817 ± 136 0.02086 Hrasls3 HRAS like suppressor 1387 ± 17 1415 ± 33 1446 ± 26 1560 ± 34 1641 ± 36 0.00000 Id3 Inhibitor of DNA binding 3, dominant negative helix-loop-helix protein 1013 ± 36 1032 ± 47 1062 ± 50 1157 ± 31 1151 ± 29 0.02512 Ifitm3 interferon induced transmembrane protein 3 212 ± 9 213 ± 9 218 ± 7 238 ± 8 247 ± 6 0.00231 Il3 interleukin 3 43 ± 3 47 ± 4 51 ± 5 54 ± 3 67 ± 5 0.00273 Il6st interleukin 6 signal transducer 341 ± 24 358 ± 18 382 ± 13 406 ± 16 465 ± 15 0.00002 Kcnd3 potassium voltage gated channel, Shal-related family, member 3 253 ± 11 250 ± 11 294 ± 6 285 ± 15 312 ± 14 0.00279 Lamp2 lysosomal membrane glycoprotein 2 1473 ± 28 1477 ± 45 1651 ± 43 1652 ± 48 1957 ± 50 0.00000 LOC252929 cathepsin Y 149 ± 5 158 ± 15 182 ± 8 190 ± 8 247 ± 19 0.00003 LOC304349 similar to cell surface receptor FDFACT 47 ± 4 43 ± 3 49 ± 6 56 ± 3 62 ± 5 0.03121 LOC309912 similar to Reticulon 4 interacting protein 1 236 ± 6 233 ± 4 247 ± 8 241 ± 7 258 ± 5 0.04047 Ltc4s leukotriene C4 synthase 316 ± 9 296 ± 16 334 ± 11 346 ± 19 388 ± 7 0.00005

Page 7 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA MGC94053 similar to RECS1 406 ± 11 404 ± 11 429 ± 18 433 ± 16 480 ± 14 0.00192 Mgst1 microsomal glutathione S-transferase 1 298 ± 16 320 ± 14 416 ± 12 382 ± 14 539 ± 28 0.00000 Mpeg1 macrophage expressed gene 1 707 ± 30 770 ± 23 814 ± 22 902 ± 26 1083 ± 47 0.00000 Msn moesin 276 ± 15 286 ± 6 300 ± 11 308 ± 14 352 ± 22 0.00792 Nedd4a neural precursor cell expressed, developmentally down-regulated gene 4A 4602 ± 64 4649 ± 125 4818 ± 96 4844 ± 99 5112 ± 165 0.02405 Nfe2l2 nuclear factor, erythroid derived 2, like 2 322 ± 8 325 ± 11 347 ± 10 351 ± 13 392 ± 11 0.00009 Nol3 nucleolar protein 3 (apoptosis repressor with CARD domain) 215 ± 7 215 ± 3 237 ± 4 241 ± 6 254 ± 6 0.00001 Nqo2 NAD(P)H dehydrogenase, quinone 2 273 ± 8 259 ± 4 277 ± 10 286 ± 8 295 ± 7 0.02016 Pgd phosphogluconate dehydrogenase 394 ± 10 387 ± 8 400 ± 10 429 ± 11 415 ± 9 0.03580 PGEA1 Cytosolic leucine-rich protein 287 ± 3 297 ± 10 335 ± 12 323 ± 18 341 ± 15 0.02518 Rpl41 ribosomal protein L41 6380 ± 101 6472 ± 84 6554 ± 120 6697 ± 141 6954 ± 154 0.02051 Rpl5 ribosomal protein L5 6733 ± 89 6838 ± 146 7002 ± 104 7165 ± 101 7446 ± 202 0.01162 S100a3 S100 calcium binding protein A3 170 ± 12 171 ± 6 183 ± 8 195 ± 6 199 ± 6 0.02162 Scpep1 serine carboxypeptidase 1 788 ± 33 815 ± 38 933 ± 53 855 ± 48 938 ± 38 0.04063 Slc12a2 solute carrier family 12, member 2 2436 ± 95 2455 ± 65 2624 ± 111 2548 ± 42 2798 ± 90 0.02207 Spa17 sperm autoantigenic protein 17 63 ± 3 64 ± 3 68 ± 4 74 ± 4 82 ± 6 0.02573 SREBP-2 Sterol regulatory element binding protein 2 997 ± 37 971 ± 26 1060 ± 19 1072 ± 31 1110 ± 28 0.00489 Stat3 signal transducer and activator of transcription 3 314 ± 17 299 ± 18 353 ± 17 360 ± 19 437 ± 18 0.00001 Tf Transferrin 4954 ± 216 5155 ± 107 5572 ± 106 5780 ± 378 6472 ± 206 0.00009 Tgfa transforming growth factor alpha 81 ± 5 79 ± 5 92 ± 5 94 ± 5 101 ± 5 0.02385 Tgfbr2 transforming growth factor, beta receptor II 417 ± 5 389 ± 7 423 ± 12 426 ± 11 458 ± 12 0.00039 Tmod1 1 190 ± 6 179 ± 12 205 ± 7 225 ± 9 221 ± 9 0.00248 Tnfsf4 tumor factor (ligand) superfamily, member 4 52 ± 2 54 ± 4 58 ± 3 67 ± 3 69 ± 4 0.00098 Tpt1 tumor protein, translationally-controlled 1 9154 ± 165 9160 ± 111 9449 ± 77 9566 ± 115 9783 ± 166 0.00743 Trip10 thyroid receptor interactor 10 102 ± 7 104 ± 4 109 ± 4 119 ± 6 122 ± 3 0.02406 Tyrobp Tyro protein tyrosine kinase binding protein 200 ± 10 193 ± 9 220 ± 12 239 ± 7 287 ± 12 0.00000 Usp2 Ubiquitin specific 2 412 ± 16 394 ± 12 474 ± 7 436 ± 14 449 ± 19 0.00841 Waspip Wiskott-Aldrich syndrome protein interacting protein 687 ± 16 657 ± 27 698 ± 32 761 ± 22 813 ± 16 0.00002 Intermediate - Downregulated 1G5 vesicle-associated calmodulin-binding protein 662 ± 23 675 ± 17 629 ± 16 617 ± 20 583 ± 26 0.03129 Adprh ADP-ribosylarginine hydrolase 547 ± 13 545 ± 18 535 ± 13 518 ± 9 495 ± 10 0.01865 Akap1 A kinase (PRKA) anchor protein 1 223 ± 4 238 ± 7 215 ± 6 212 ± 5 214 ± 6 0.02077 Ap2b1 adaptor-related protein complex 2, beta 1 subunit 898 ± 22 964 ± 21 882 ± 21 872 ± 34 819 ± 26 0.00606 Bk B/K protein 1137 ± 26 1214 ± 18 1109 ± 34 1123 ± 37 1046 ± 40 0.01748

Page 8 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Capzb F- capping protein beta subunit 3090 ± 83 3239 ± 79 2928 ± 128 2964 ± 54 2826 ± 70 0.01358 Cdk5r cyclin-dependent kinase 5, regulatory subunit 1 (p35) 278 ± 5 293 ± 9 254 ± 6 254 ± 8 223 ± 7 0.00000 Dcn decorin 472 ± 26 496 ± 17 426 ± 29 454 ± 26 406 ± 15 0.04021 Dpp6 dipeptidylpeptidase 6 777 ± 35 782 ± 42 735 ± 15 724 ± 23 632 ± 17 0.00123 Faah fatty acid amide hydrolase 488 ± 14 481 ± 7 472 ± 9 454 ± 8 457 ± 7 0.03939 Fkbp4 FK506 binding protein 4 836 ± 26 848 ± 35 789 ± 19 812 ± 19 744 ± 20 0.02063 Giot1 gonadotropin inducible ovarian transcription factor 1 31 ± 4 33 ± 3 25 ± 4 22 ± 1 22 ± 2 0.01782 Grin1 glutamate receptor, ionotropic, N-methyl D-aspartate 1 1148 ± 45 1156 ± 35 998 ± 27 1074 ± 53 1030 ± 23 0.01602 Hdh Huntington disease gene homolog 273 ± 6 273 ± 12 239 ± 6 235 ± 15 242 ± 7 0.01146 Iars isoleucine-tRNA synthetase 70 ± 4 67 ± 3 62 ± 5 50 ± 5 48 ± 2 0.00022 Kcnip4 potassium channel interacting protein 4 405 ± 8 427 ± 12 382 ± 13 369 ± 7 335 ± 11 0.00000 Kcnma1 potassium large conductance calcium-activated channel, subfamily M, alpha membe 131 ± 5 137 ± 7 126 ± 6 124 ± 2 114 ± 4 0.01249 Kcnv1 potassium channel, subfamily V, member 1 617 ± 22 609 ± 16 583 ± 24 578 ± 15 533 ± 18 0.01918 Kidins220 kinase D-interacting substance 220 525 ± 15 552 ± 11 515 ± 17 519 ± 9 494 ± 13 0.04951 LOC286890 tropomyosin isoform 6 501 ± 15 528 ± 14 458 ± 15 485 ± 18 475 ± 14 0.04153 LOC298359 similar to HUD3 950 ± 40 959 ± 27 912 ± 48 875 ± 34 831 ± 26 0.05372 LOC300149 similar to hypothetical protein MGC18000 389 ± 21 388 ± 20 333 ± 10 328 ± 17 332 ± 18 0.03387 LOC362040 similar to RIKEN cDNA 2310008M10 641 ± 18 631 ± 24 616 ± 24 613 ± 16 568 ± 9 0.03848 Lum lumican 115 ± 6 118 ± 7 106 ± 7 98 ± 7 95 ± 4 0.02770 Mal2 Mal, T-cell differentiation protein 2 2176 ± 60 2228 ± 90 2062 ± 70 2104 ± 80 1869 ± 26 0.00192 Mark3 MAP/ affinity-regulating kinase 3 787 ± 25 793 ± 39 737 ± 21 727 ± 25 702 ± 15 0.05013 MGC93965 similar to Probable RNA-dependent helicase p68 (DEAD-box protein p68) (DEAD-bo 3345 ± 62 3352 ± 79 3303 ± 59 3180 ± 34 3147 ± 64 0.05405 Pik4cb phosphatidylinositol 4-kinase, catalytic, beta polypeptide 514 ± 10 524 ± 18 465 ± 37 458 ± 25 395 ± 18 0.00123 Ptpro protein tyrosine phosphatase, receptor type, O 260 ± 10 252 ± 8 225 ± 14 217 ± 8 223 ± 9 0.01058 Rap2b RAP2B, member of RAS oncogene family 180 ± 8 198 ± 9 179 ± 5 167 ± 5 149 ± 5 0.00004 Slc15a4 peptide/histidine transporter 313 ± 7 320 ± 16 286 ± 6 299 ± 9 279 ± 11 0.03081 Slc31a1 solute carrier family 31 (copper transporters), member 1 112 ± 7 109 ± 5 95 ± 6 91 ± 3 92 ± 4 0.02055 Slc7a10 solute carrier family 7 (cationic amino acid transporter, y+ system), member 10 363 ± 16 356 ± 11 337 ± 9 304 ± 11 328 ± 10 0.01237 Spata2 Spermatogenesis associated 2 192 ± 7 198 ± 7 174 ± 10 167 ± 6 164 ± 6 0.00255 Spon1 spondin 1 1840 ± 30 1915 ± 32 1824 ± 59 1770 ± 50 1720 ± 37 0.02493 Sv2b synaptic vesicle glycoprotein 2b 1480 ± 75 1501 ± 45 1379 ± 41 1297 ± 34 1265 ± 24 0.00075 Tfrc Transferrin receptor 1984 ± 80 1942 ± 35 1823 ± 62 1770 ± 40 1827 ± 26 0.02743 Midlife - Upregulated A2m alpha-2-macroglobulin 262 ± 7 272 ± 8 244 ± 6 290 ± 7 353 ± 16 0.00000

Page 9 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Abcb1a ATP-binding cassette, sub-family B (MDR/TAP), member 1A 136 ± 8 147 ± 6 147 ± 13 155 ± 9 185 ± 13 0.01272 Actb actin, beta 12965 ± 310 13382 ± 170 13145 ± 273 13739 ± 303 14187 ± 269 0.01195 Angptl4 angiopoietin-like protein 4 142 ± 8 153 ± 8 152 ± 7 176 ± 8 172 ± 8 0.01142 Anxa3 1094 ± 41 1203 ± 27 1181 ± 34 1301 ± 26 1561 ± 46 0.00000 Apoe apolipoprotein E 13561 ± 455 14438 ± 199 13789 ± 368 15176 ± 432 15953 ± 360 0.00009 arhgef6 Rac/cdc42 guanine nucleotide exchange factor 6 327 ± 18 362 ± 13 337 ± 8 356 ± 15 389 ± 8 0.00553 Arpc1b actin related protein 2/3 complex, subunit 1B 225 ± 6 231 ± 8 210 ± 5 242 ± 6 266 ± 9 0.00001 Ascl1 achaete-scute complex homolog-like 1 (Drosophila) 97 ± 4 90 ± 6 94 ± 4 98 ± 5 110 ± 4 0.02268 Atp6k ATPase, H+ transporting, V0 subunit 744 ± 22 780 ± 35 754 ± 37 826 ± 29 869 ± 28 0.02042 B2m beta-2 microglobulin 5709 ± 118 5934 ± 123 5888 ± 75 6408 ± 108 6911 ± 124 0.00000 Bmp7 bone morphogenetic protein 7 107 ± 2 111 ± 5 104 ± 5 120 ± 6 136 ± 7 0.00167 Ca3 carbonic anhydrase 3 58 ± 3 53 ± 4 60 ± 3 74 ± 3 89 ± 5 0.00000 Cd14 CD14 antigen 50 ± 5 51 ± 3 51 ± 3 64 ± 3 71 ± 5 0.00071 Cd3z CD3 antigen, zeta polypeptide 80 ± 7 85 ± 8 69 ± 5 99 ± 8 92 ± 5 0.03195 Cd63 CD63 antigen 1525 ± 34 1600 ± 39 1582 ± 50 1716 ± 47 2082 ± 40 0.00000 Cd81 CD 81 antigen 9149 ± 171 9677 ± 357 9490 ± 204 9734 ± 384 10378 ± 281 0.04417 Cd86 CD86 antigen 24 ± 5 32 ± 6 29 ± 3 44 ± 3 55 ± 4 0.00001 Cdh23 cadherin 23 (otocadherin) 73 ± 5 99 ± 8 82 ± 6 109 ± 4 123 ± 6 0.00000 Clu clusterin 7672 ± 178 7774 ± 204 7830 ± 173 8404 ± 246 8532 ± 186 0.00560 Csrp1 cysteine and glycine-rich protein 1 1692 ± 53 1755 ± 59 1748 ± 28 1894 ± 76 1858 ± 35 0.04695 Cst3 cystatin C 13229 ± 240 13297 ± 342 13667 ± 215 13984 ± 364 15084 ± 367 0.00059 Ctsd cathepsin D 2315 ± 45 2421 ± 52 2458 ± 63 2600 ± 66 2958 ± 63 0.00000 Ctss cathepsin S 3820 ± 115 3963 ± 181 4100 ± 105 4665 ± 228 5585 ± 182 0.00000 Eef1a1 eukaryotic translation elongation factor 1 alpha 1 1663 ± 27 1696 ± 46 1683 ± 20 1785 ± 21 1791 ± 21 0.00337 Eef1d Translation elongation factor 1-delta subunit 1123 ± 29 1137 ± 25 1135 ± 17 1175 ± 29 1222 ± 28 0.04534 Ehd4 EH-domain containing 4 264 ± 11 259 ± 14 259 ± 11 302 ± 13 288 ± 8 0.03185 Eif4ebp1 eukaryotic translation initiation factor 4E binding protein 1 312 ± 14 311 ± 10 280 ± 9 369 ± 9 341 ± 13 0.00011 Fth1 ferritin, heavy polypeptide 1 15862 ± 403 15870 ± 245 16210 ± 336 16709 ± 584 18249 ± 449 0.00040 Ftl1 ferritin light chain 1 1991 ± 31 2115 ± 35 2102 ± 19 2254 ± 70 2417 ± 58 0.00000 Fxyd1 FXYD domain-containing ion transport regulator 1 695 ± 28 730 ± 34 703 ± 30 796 ± 26 959 ± 25 0.00000 Fxyd5 FXYD domain-containing ion transport regulator 5 106 ± 4 102 ± 6 95 ± 10 110 ± 9 128 ± 5 0.01225 Galc Galactosylceramidase 367 ± 11 390 ± 11 374 ± 7 399 ± 11 406 ± 10 0.04896 Galm galactose mutarotase (aldose 1-epimerase) 135 ± 5 131 ± 5 128 ± 4 139 ± 4 158 ± 7 0.00093 Gcnt2 glucosaminyl (N-acetyl) transferase 2, I-branching enzyme 172 ± 7 170 ± 8 169 ± 4 191 ± 7 200 ± 6 0.00217

Page 10 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Gfap glial fibrillary acidic protein 6208 ± 134 6534 ± 134 6408 ± 129 6901 ± 228 8198 ± 262 0.00000 Ggta1 Glycoprotein galactosyltransferase alpha 1, 3 191 ± 9 195 ± 9 183 ± 7 239 ± 8 266 ± 9 0.00000 Gipr gastric inhibitory polypeptide receptor 96 ± 6 98 ± 10 96 ± 6 118 ± 8 132 ± 6 0.00104 Gp38 glycoprotein 38 457 ± 13 461 ± 19 460 ± 19 506 ± 24 534 ± 11 0.00407 Gpr37l1 G protein-coupled receptor 37-like 1 2541 ± 64 2557 ± 80 2583 ± 44 2682 ± 66 2825 ± 53 0.00562 Grn granulin 930 ± 34 937 ± 22 944 ± 18 1001 ± 20 1100 ± 31 0.00006 Hk2 hexokinase 2 92 ± 5 106 ± 4 91 ± 6 118 ± 7 124 ± 8 0.00109 Hla-dmb major histocompatibility complex, class II, DM beta 399 ± 13 376 ± 14 400 ± 16 420 ± 5 461 ± 18 0.00138 Igsf1 immunoglobulin superfamily, member 1 514 ± 35 534 ± 23 521 ± 19 569 ± 23 634 ± 30 0.00975 Itih3 inter-alpha trypsin inhibitor, heavy chain 3 3657 ± 171 4117 ± 131 3952 ± 177 4338 ± 85 5172 ± 243 0.00000 Lamr1 laminin receptor 1 (67kD, ribosomal protein SA) 4165 ± 102 4191 ± 96 4065 ± 50 4412 ± 74 4394 ± 82 0.02083 Laptm5 lysosomal-associated protein transmembrane 5 279 ± 6 313 ± 15 319 ± 11 346 ± 13 420 ± 16 0.00000 Lcat lecithin cholesterol acyltransferase 331 ± 28 347 ± 26 355 ± 17 414 ± 16 425 ± 19 0.00659 LOC288707 similar to Glycolipid transfer protein 869 ± 19 891 ± 38 899 ± 31 934 ± 25 997 ± 21 0.00827 LOC306920 similar to RIKEN cDNA 1190005B03 219 ± 10 209 ± 4 203 ± 9 244 ± 10 229 ± 6 0.00732 LOC307403 similar to Macrophage colony stimulating factor I receptor precursor (CSF-1-R) (Fms 635 ± 24 687 ± 17 649 ± 23 716 ± 24 814 ± 21 0.00000 LOC310756 similar to Potentail helicase MOV-10 68 ± 10 78 ± 8 67 ± 5 80 ± 8 99 ± 8 0.02986 LOC315085 nicotinate phosphoribosyltransferase-like protein 373 ± 9 402 ± 20 392 ± 8 414 ± 18 461 ± 13 0.00051 LOC362288 Similar to helicase-like protein NHL isoform 2 51 ± 4 48 ± 4 46 ± 2 57 ± 4 61 ± 5 0.04036 LOC362704 brain and reproductive organ-expressed protein 344 ± 6 343 ± 11 344 ± 8 360 ± 4 370 ± 6 0.03081 Lyz lysozyme 1107 ± 22 1138 ± 42 1128 ± 39 1204 ± 46 1427 ± 39 0.00000 Masp1 mannan-binding lectin serine peptidase 1 153 ± 10 165 ± 8 159 ± 5 171 ± 9 189 ± 8 0.02010 MGC93733 similar to RIKEN cDNA 6530411B15 249 ± 7 268 ± 9 261 ± 9 294 ± 15 313 ± 11 0.00031 Mgp 320 ± 10 302 ± 13 289 ± 14 322 ± 12 360 ± 18 0.00714 Mobp myelin-associated oligodendrocytic basic protein 8929 ± 198 8917 ± 211 9045 ± 182 9443 ± 366 10068 ± 388 0.03329 Mog Myelin oligodendrocyte glycoprotein 204 ± 13 245 ± 9 215 ± 8 260 ± 21 266 ± 12 0.00585 Mrlcb Myosin regulatory light chain 756 ± 32 741 ± 24 709 ± 34 779 ± 37 885 ± 44 0.01002 Mt3 metallothionein 3 8844 ± 250 8987 ± 125 8940 ± 96 9511 ± 239 9855 ± 267 0.00644 P2ry6 pyrimidinergic receptor P2Y, G-protein coupled, 6 178 ± 11 186 ± 10 181 ± 7 214 ± 15 208 ± 8 0.05312 P2y12 purinergic receptor P2Y, G-protein coupled 12 257 ± 14 296 ± 20 271 ± 18 305 ± 15 360 ± 11 0.00010 Pace4 Subtilisin - like endoprotease 246 ± 11 252 ± 4 242 ± 9 264 ± 11 283 ± 6 0.00503 Pcyt1a phosphate cytidylyltransferase 1, choline, alpha isoform 305 ± 8 287 ± 7 300 ± 9 310 ± 11 328 ± 11 0.05471 Pld1 phospholipase D1 203 ± 7 207 ± 13 205 ± 8 216 ± 11 246 ± 11 0.01580 Plec1 1 564 ± 24 539 ± 12 571 ± 22 602 ± 15 655 ± 23 0.00231

Page 11 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Prkch protein kinase C, eta 135 ± 5 141 ± 4 133 ± 3 146 ± 8 156 ± 5 0.01549 Pros1 protein S (alpha) 120 ± 8 116 ± 8 116 ± 6 131 ± 6 156 ± 9 0.00109 Psmb8 proteosome (prosome, macropain) subunit, beta type 8 105 ± 6 109 ± 5 105 ± 4 113 ± 7 124 ± 5 0.04021 Psme2 protease (prosome, macropain) 28 subunit, beta 574 ± 15 566 ± 15 581 ± 15 637 ± 22 643 ± 13 0.00095 Rpo1-4 RNA polymerase 1-4 116 ± 8 110 ± 8 107 ± 5 136 ± 6 131 ± 5 0.00838 Rps19 ribosomal protein S19 7889 ± 204 7801 ± 105 7919 ± 79 8453 ± 136 8566 ± 224 0.00702 RT1-Aw2 RT1 class Ib, Aw2 617 ± 30 688 ± 39 620 ± 19 694 ± 32 818 ± 59 0.00433 RT1-M3 RT1 class Ib, locus M3 395 ± 14 372 ± 10 356 ± 14 414 ± 17 413 ± 9 0.00837 S100a4 S100 calcium-binding protein A4 309 ± 10 316 ± 21 296 ± 11 376 ± 30 499 ± 23 0.00000 Scn10a sodium channel, voltage-gated, type 10, alpha polypeptide 57 ± 7 76 ± 9 63 ± 4 73 ± 6 93 ± 8 0.00652 Sfrs5 splicing factor, arginine/serine-rich 5 2967 ± 89 3045 ± 140 3062 ± 96 3285 ± 168 3426 ± 76 0.02674 Siat7A sialyltransferase 7 ((alpha-N-acetylneuraminyl 2,3-beta-galactosyl-1,3)-N-acetyl gala 173 ± 9 190 ± 6 178 ± 6 193 ± 7 203 ± 8 0.03835 Siat7c sialyltransferase 7c 234 ± 11 250 ± 10 241 ± 8 272 ± 8 265 ± 8 0.02548 Slc15a3 peptide/histidine transporter PHT2 62 ± 5 64 ± 6 64 ± 4 74 ± 7 91 ± 6 0.00239 Smoc1 SPARC-related modular calcium binding protein 1 157 ± 9 167 ± 7 168 ± 10 195 ± 5 217 ± 8 0.00001 Sod3 superoxide dismutase 3, extracellular 380 ± 9 383 ± 17 360 ± 11 409 ± 7 420 ± 12 0.00378 Srebf1 sterol regulatory element binding factor 1 572 ± 20 604 ± 26 593 ± 18 657 ± 19 682 ± 28 0.00716 Tbxas1 thromboxane A synthase 1 130 ± 7 151 ± 9 140 ± 6 166 ± 11 190 ± 9 0.00005 Tcn2 transcobalamin 2 444 ± 20 464 ± 13 454 ± 11 471 ± 10 499 ± 14 0.05438 Tgfbi Transforming growth factor, beta induced, 68 kDa 100 ± 6 108 ± 8 107 ± 2 122 ± 7 119 ± 5 0.05331 Timp2 tissue inhibitor of metalloproteinase 2 1220 ± 49 1351 ± 40 1284 ± 45 1354 ± 30 1490 ± 51 0.00115 Torid TORID 1908 ± 109 2006 ± 103 2076 ± 73 2202 ± 75 2673 ± 125 0.00001 Tpm4 tropomyosin 4 180 ± 7 163 ± 13 145 ± 7 198 ± 14 202 ± 16 0.01813 Ugt1a1 UDP glycosyltransferase 1 family, polypeptide A1 122 ± 7 111 ± 6 106 ± 6 124 ± 9 135 ± 4 0.00810 Vamp5 vesicle-associated membrane protein 5 132 ± 6 125 ± 5 126 ± 4 137 ± 7 148 ± 7 0.03894 Xrcc1 X-ray repair complementing defective repair in Chinese hamster cells 1 301 ± 8 308 ± 17 292 ± 6 333 ± 9 325 ± 8 0.04734 Midlife - Downregulated Ap2s1 adaptor-related protein complex 2, sigma 1 subunit 1705 ± 17 1716 ± 28 1716 ± 40 1674 ± 45 1600 ± 27 0.04242 App amyloid beta (A4) precursor protein 4957 ± 118 4925 ± 105 4916 ± 64 4786 ± 119 4582 ± 91 0.03941 Arl1 ADP-ribosylation factor-like 1 1280 ± 38 1252 ± 35 1303 ± 24 1232 ± 43 1159 ± 23 0.01857 Atp2b2 ATPase, Ca++ transporting, plasma membrane 2 406 ± 22 394 ± 21 403 ± 16 362 ± 15 348 ± 9 0.04121 Cdc42 cell division cycle 42 homolog (S. cerevisiae) 3701 ± 54 3545 ± 75 3680 ± 108 3455 ± 67 3427 ± 68 0.04113 Chga chromogranin A 809 ± 30 769 ± 29 801 ± 21 712 ± 30 690 ± 21 0.00433 Cntn4 contactin 4 528 ± 17 537 ± 22 519 ± 17 506 ± 11 463 ± 14 0.01074

Page 12 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Dlat dihydrolipoamide S-acetyltransferase (E2 component of pyruvate dehydrogenase co 996 ± 31 951 ± 16 1011 ± 34 915 ± 27 907 ± 17 0.01345 Dlgh3 Discs, large homolog 3 (Drosophila) 461 ± 18 462 ± 23 464 ± 10 418 ± 16 362 ± 12 0.00003 Dmtf1 Cyclin D binding myb-like transcription factor 1 802 ± 24 819 ± 23 823 ± 16 776 ± 23 730 ± 17 0.00783 Dnaja1 DnaJ-like protein 3090 ± 72 2974 ± 62 3034 ± 55 2935 ± 58 2750 ± 36 0.00029 Dnm1l dynamin 1-like 185 ± 13 165 ± 10 186 ± 12 163 ± 12 142 ± 5 0.01602 Gpcr12 G-protein coupled receptor 12 388 ± 10 368 ± 15 395 ± 14 359 ± 10 341 ± 13 0.02552 Gprk6 G protein-coupled receptor kinase 6 91 ± 8 85 ± 7 91 ± 4 77 ± 3 69 ± 5 0.02009 Grm7 glutamate receptor, metabotropic 7 264 ± 11 264 ± 12 264 ± 6 242 ± 4 235 ± 8 0.03876 Gspt1 G1 to S phase transition 1 1370 ± 17 1353 ± 26 1394 ± 20 1328 ± 32 1277 ± 16 0.00367 Ighmbp2 immunoglobulin mu binding protein 2 124 ± 9 122 ± 5 136 ± 4 104 ± 7 97 ± 8 0.00196 Kif3c family member 3C 1673 ± 35 1661 ± 20 1661 ± 31 1580 ± 33 1545 ± 31 0.01028 Kit v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog 345 ± 18 330 ± 15 335 ± 11 305 ± 17 280 ± 10 0.00917 LOC289182 similar to Brain protein 44 (0-44 protein) 2046 ± 60 2000 ± 50 2033 ± 43 1932 ± 57 1825 ± 31 0.00615 LOC290939_p similar to DNA segment, Chr 13, Wayne State University 50, expressed (predicted) 551 ± 16 535 ± 15 537 ± 13 494 ± 11 507 ± 14 0.03987 LOC292995 similar to BBP-like protein 2 1566 ± 18 1557 ± 27 1585 ± 31 1473 ± 34 1420 ± 13 0.00001 LOC299707 similar to RIKEN cDNA 2900091E11 507 ± 22 527 ± 20 558 ± 16 497 ± 28 446 ± 20 0.00559 LOC311254 similar to Ac1164 394 ± 9 396 ± 9 397 ± 16 372 ± 10 357 ± 7 0.01756 Map2k6 mitogen-activated protein kinase kinase 6 483 ± 12 501 ± 20 495 ± 12 481 ± 16 446 ± 11 0.04860 Mapk1 mitogen activated protein kinase 1 2113 ± 52 2184 ± 50 2234 ± 32 1956 ± 78 1974 ± 55 0.00322 Mas1 MAS1 oncogene 504 ± 28 504 ± 16 512 ± 32 455 ± 16 403 ± 19 0.00324 MGC95290 similar to senescence downregulated leo1-like 100 ± 4 89 ± 6 100 ± 8 82 ± 6 80 ± 5 0.04119 Minpp1 multiple inositol polyphosphate histidine phosphatase 1 872 ± 15 868 ± 22 894 ± 13 818 ± 24 842 ± 13 0.04400 Nap1l3 nucleosome assembly protein 1-like 3 588 ± 18 563 ± 20 593 ± 19 517 ± 13 524 ± 13 0.00360 Nfl , light polypeptide 3409 ± 57 3472 ± 81 3579 ± 58 3383 ± 87 3253 ± 75 0.03639 Nudt4 nudix (nucleoside diphosphate linked moiety X)-type motif 4 2057 ± 40 2042 ± 39 2016 ± 37 2003 ± 33 1898 ± 28 0.00978 Nup153 153kD 353 ± 20 334 ± 18 361 ± 13 292 ± 12 306 ± 14 0.01321 Nup62 nucleoporin 62 418 ± 9 399 ± 13 421 ± 12 383 ± 10 390 ± 6 0.03122 Pak1 p21 (CDKN1A)-activated kinase 1 473 ± 31 447 ± 10 455 ± 20 426 ± 23 363 ± 10 0.00146 Pkia Protein kinase inhibitor, alpha 606 ± 28 567 ± 32 617 ± 20 532 ± 19 459 ± 20 0.00006 Ppid peptidylprolyl isomerase D 2035 ± 31 1952 ± 68 2046 ± 29 1924 ± 40 1873 ± 39 0.03046 Ppp1r10 protein phosphatase 1, regulatory subunit 10 318 ± 9 313 ± 12 308 ± 10 282 ± 13 285 ± 7 0.03404 Ppp1r2 Protein phosphatase 1, regulatory (inhibitor) subunit 2 2271 ± 21 2235 ± 83 2277 ± 36 2200 ± 70 2061 ± 38 0.02081 Ptprd protein tyrosine phosphatase, receptor type, D 464 ± 20 480 ± 12 465 ± 15 441 ± 11 410 ± 9 0.00396 Rac1 ras-related C3 botulinum toxin substrate 1 2016 ± 41 1982 ± 37 2004 ± 30 1935 ± 45 1861 ± 32 0.01903

Page 13 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Rasgrp1 RAS guanyl releasing protein 1 1096 ± 23 1115 ± 47 1066 ± 33 1023 ± 53 908 ± 34 0.00202 Rfng radical fringe gene homolog (Drosophila) 228 ± 14 218 ± 13 225 ± 10 209 ± 6 183 ± 6 0.01290 Rgs14 regulator of G-protein signaling 14 1077 ± 47 1033 ± 28 1051 ± 27 979 ± 13 941 ± 23 0.00876 Rnf138 ring finger protein 138 116 ± 5 115 ± 7 122 ± 3 102 ± 11 94 ± 5 0.01774 Rnf4 Ring finger protein 4 708 ± 16 713 ± 19 723 ± 14 689 ± 25 641 ± 18 0.01324 Sara1 SAR1a gene homolog 1 820 ± 19 781 ± 14 848 ± 13 787 ± 32 724 ± 24 0.00227 Scamp1 secretory carrier membrane protein 1 1522 ± 29 1495 ± 39 1521 ± 37 1428 ± 49 1368 ± 26 0.00760 Scamp3 secretory carrier membrane protein 3 609 ± 25 633 ± 23 600 ± 20 591 ± 20 523 ± 16 0.00299 Sfpq NonO/p54nrb homolog 336 ± 10 337 ± 16 349 ± 12 304 ± 11 296 ± 10 0.00839 Slc21a13 solute carrier family 21, member 13 18 ± 4 21 ± 4 22 ± 4 12 ± 2 10 ± 2 0.04404 Synpr synaptoporin 893 ± 57 858 ± 30 931 ± 61 787 ± 36 740 ± 26 0.01597 Syt5 5 950 ± 25 939 ± 21 936 ± 14 914 ± 18 875 ± 20 0.05412 Tip120A TBP-interacting protein 120A 1648 ± 25 1576 ± 38 1657 ± 28 1543 ± 24 1537 ± 24 0.00567 Tpm1 tropomyosin 1, alpha 551 ± 13 541 ± 12 541 ± 10 491 ± 23 490 ± 20 0.02787 Trim23 tripartite motif protein 23 412 ± 21 419 ± 15 442 ± 18 392 ± 11 362 ± 15 0.00831 Ube2v2 ubiquitin-conjugating enzyme E2 variant 2 935 ± 40 889 ± 35 926 ± 26 847 ± 45 798 ± 29 0.03180 Ubqln1 ubiquilin 1 1027 ± 19 1006 ± 23 1021 ± 16 982 ± 13 946 ± 15 0.00452 Unc5a unc-5 homolog A (C. elegans) 215 ± 14 222 ± 9 236 ± 5 191 ± 17 177 ± 13 0.01001 Vgcnl1 voltage gated channel like 1 1457 ± 23 1436 ± 36 1467 ± 20 1412 ± 28 1349 ± 27 0.02014 Late - Upregulated Acadvl acyl-Coenzyme A dehydrogenase, very long chain 426 ± 14 414 ± 10 404 ± 13 411 ± 15 461 ± 10 0.01017 Acvrinp1 activin receptor interacting protein 1 304 ± 18 285 ± 21 274 ± 13 297 ± 21 341 ± 14 0.03610 Agt angiotensinogen 947 ± 36 1019 ± 52 976 ± 41 1008 ± 36 1137 ± 43 0.01632 Aif1 allograft inflammatory factor 1 193 ± 4 205 ± 10 218 ± 9 210 ± 9 285 ± 15 0.00000 Anp32b acidic nuclear phosphoprotein 32 family, member B 1256 ± 20 1269 ± 21 1296 ± 17 1277 ± 24 1367 ± 39 0.04200 Apobec1 apolipoprotein B editing complex 1 55 ± 4 60 ± 4 65 ± 7 61 ± 7 85 ± 5 0.00136 Arrdc3 Arrestin domain containing 3 503 ± 12 514 ± 19 549 ± 21 523 ± 20 606 ± 25 0.00405 Bche butyrylcholinesterase 59 ± 4 54 ± 6 56 ± 4 53 ± 3 68 ± 4 0.04016 Bzrp benzodiazepin receptor 155 ± 4 137 ± 10 148 ± 5 150 ± 8 189 ± 9 0.00017 C1s complement component 1, s subcomponent 129 ± 7 128 ± 8 122 ± 6 120 ± 8 155 ± 7 0.00304 C4-2 complement component 4a 108 ± 5 124 ± 7 140 ± 8 147 ± 7 231 ± 16 0.00000 Casp4 caspase 11 85 ± 5 93 ± 4 81 ± 5 80 ± 4 107 ± 4 0.00025 Cav caveolin 517 ± 16 528 ± 13 523 ± 18 537 ± 25 593 ± 13 0.01031 Ccdc5 coiled-coil domain containing 5 107 ± 6 103 ± 5 110 ± 5 107 ± 6 123 ± 5 0.04913

Page 14 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Ccnd1 cyclin D1 187 ± 10 170 ± 4 181 ± 14 169 ± 9 216 ± 13 0.01481 Cd37 CD37 antigen 83 ± 5 82 ± 5 78 ± 5 85 ± 5 104 ± 4 0.00069 Cd48 CD48 antigen 454 ± 10 445 ± 18 427 ± 19 438 ± 11 508 ± 16 0.00273 Cd74 CD74 antigen (invariant polpypeptide of major histocompatibility class II antigen-asso 183 ± 5 176 ± 11 160 ± 7 220 ± 7 529 ± 45 0.00000 Cdc10 CDC10 (cell division cycle 10, S.cerevisiae, homolog) 7086 ± 142 6667 ± 344 7184 ± 324 6853 ± 160 7668 ± 219 0.04987 Cfh complement component factor h 177 ± 4 194 ± 8 203 ± 4 210 ± 13 272 ± 12 0.00000 Cib1 calcium and integrin binding 1 (calmyrin) 334 ± 11 350 ± 12 325 ± 12 341 ± 17 413 ± 10 0.00001 Cklfsf6 Chemokine-like factor superfamily 6 136 ± 7 127 ± 7 128 ± 5 127 ± 6 152 ± 7 0.02451 Cml5 camello-like 5 192 ± 13 209 ± 11 203 ± 6 209 ± 10 237 ± 11 0.04030 Cnn3 calponin 3, acidic 1625 ± 37 1544 ± 35 1580 ± 45 1625 ± 56 1806 ± 72 0.00619 Cplx2 complexin 2 464 ± 29 463 ± 30 487 ± 29 483 ± 20 555 ± 20 0.04225 Cryac crystallin, alpha C 181 ± 11 197 ± 8 195 ± 7 196 ± 6 219 ± 9 0.03032 Cyba cytochrome b-245, alpha polypeptide 272 ± 3 272 ± 6 284 ± 6 281 ± 7 349 ± 12 0.00000 Cyp2a3a Cytochrome P450, subfamily IIA (phenobarbital-inducble)/ (Cytochrome P450 IIA3) 27 ± 4 33 ± 3 36 ± 4 29 ± 4 44 ± 4 0.02017 Cyp3a13 cytochrome P450, family 3, subfamily a, polypeptide 13 120 ± 4 128 ± 11 128 ± 4 131 ± 10 153 ± 7 0.03125 Dhrs4 dehydrogenase/reductase (SDR family) member 4 191 ± 6 185 ± 6 201 ± 3 197 ± 8 226 ± 8 0.00035 Dhx40 DEAH (Asp-Glu-Ala-His) box polypeptide 40 305 ± 10 302 ± 10 307 ± 11 293 ± 10 339 ± 10 0.01434 Echdc1 enoyl Coenzyme A hydratase domain containing 1 908 ± 29 899 ± 12 931 ± 37 909 ± 35 1012 ± 22 0.02474 Ednrb endothelin receptor type B 575 ± 23 558 ± 27 621 ± 23 629 ± 32 813 ± 72 0.00235 Egfr epidermal growth factor receptor 490 ± 7 503 ± 16 480 ± 13 480 ± 14 538 ± 16 0.01426 Eif2c2 GERp95 107 ± 10 99 ± 8 115 ± 10 105 ± 9 151 ± 15 0.00988 Eif5 eukaryotic translation initiation factor 5 2484 ± 72 2516 ± 81 2679 ± 103 2601 ± 97 2916 ± 133 0.03311 F3 coagulation factor 3 307 ± 11 299 ± 14 317 ± 17 322 ± 15 373 ± 18 0.00949 Faf1 Fas-associated factor 1 429 ± 14 439 ± 23 443 ± 22 428 ± 16 491 ± 13 0.04066 Fnbp1 rapostlin 119 ± 7 123 ± 8 126 ± 6 119 ± 6 154 ± 6 0.00036 Fuca fucosidase, alpha-L- 1, tissue 928 ± 15 945 ± 21 938 ± 13 925 ± 10 1032 ± 21 0.00009 Gabrp gamma-aminobutyric acid (GABA) A receptor, pi 22 ± 2 25 ± 3 24 ± 3 19 ± 4 33 ± 2 0.01349 Galnt7 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 151 ± 8 152 ± 7 160 ± 9 152 ± 5 183 ± 9 0.01940 Gpnmb glycoprotein (transmembrane) nmb 189 ± 9 210 ± 10 213 ± 13 238 ± 11 375 ± 14 0.00000 Gpx1 glutathione peroxidase 1 1670 ± 96 1585 ± 45 1781 ± 37 1719 ± 28 1983 ± 54 0.00010 Gria2 glutamate receptor, ionotropic, 2 4768 ± 157 4547 ± 230 4735 ± 117 4725 ± 225 5373 ± 234 0.03744 Grm3 glutamate receptor, metabotropic 3 1255 ± 43 1148 ± 60 1287 ± 52 1242 ± 61 1483 ± 80 0.00711 Gsn 1502 ± 49 1479 ± 39 1472 ± 30 1489 ± 69 1677 ± 38 0.00526 Gsta5 glutathione S-transferase A5 1740 ± 41 1734 ± 46 1850 ± 30 1797 ± 34 2055 ± 55 0.00001

Page 15 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Hmgn2 high mobility group protein 17 2507 ± 54 2428 ± 74 2558 ± 41 2524 ± 59 2696 ± 36 0.00834 Il18 interleukin 18 108 ± 7 109 ± 3 109 ± 3 113 ± 7 140 ± 6 0.00016 Kif1c kinesin family member 1C 548 ± 23 562 ± 19 539 ± 12 547 ± 18 641 ± 19 0.00037 Lgals3 lectin, galactose binding, soluble 3 46 ± 8 67 ± 7 57 ± 4 55 ± 9 107 ± 9 0.00000 Lgals8 lectin, galactose binding, soluble 8 563 ± 24 547 ± 28 563 ± 35 555 ± 31 658 ± 17 0.01561 LOC294917 similar to misshapen/NIK-related kinase isoform 2; GCK family kinase MINK; serine/t 394 ± 13 411 ± 16 397 ± 15 407 ± 14 461 ± 18 0.01101 LOC301443 similar to Bone morphogenetic protein type II receptor 381 ± 18 332 ± 37 380 ± 33 383 ± 33 507 ± 50 0.02066 LOC303571 similar to glycoprotein IIb - rat 152 ± 7 142 ± 6 154 ± 6 155 ± 13 198 ± 13 0.00246 LOC309499 similar to Myoferlin (Fer-1 like protein 3) 60 ± 4 64 ± 5 57 ± 2 63 ± 4 75 ± 5 0.04693 LOC313245 similar to RNA polymerase I associated factor (PAF53) 167 ± 10 176 ± 9 172 ± 10 171 ± 12 207 ± 7 0.01600 LOC360934 similar to ENSANGP00000012385 253 ± 10 265 ± 13 267 ± 7 284 ± 7 353 ± 11 0.00000 LOC64038 sertolin 36 ± 4 37 ± 4 27 ± 2 34 ± 4 48 ± 5 0.00790 Mdk midkine 567 ± 30 550 ± 14 552 ± 10 567 ± 12 618 ± 19 0.03539 MGC94557 similar to MS4A6B protein 83 ± 3 92 ± 4 100 ± 7 98 ± 5 129 ± 3 0.00000 Mt1a Metallothionein 383 ± 31 412 ± 45 405 ± 41 422 ± 24 661 ± 40 0.00000 Mx1 myxovirus (influenza virus) resistance 1 45 ± 3 45 ± 3 40 ± 2 42 ± 5 61 ± 4 0.00065 Myo1c myosin IC 218 ± 5 228 ± 7 229 ± 4 218 ± 8 249 ± 9 0.00978 Ncl nucleolin 1192 ± 31 1215 ± 45 1239 ± 50 1225 ± 37 1344 ± 32 0.04299 Ndrg2 N-myc downstream regulated gene 2 11420 ± 337 11059 ± 412 11128 ± 195 11166 ± 389 12532 ± 473 0.03852 Nek6 NIMA (never in mitosis gene a)-related expressed kinase 6 292 ± 14 296 ± 13 326 ± 5 289 ± 12 364 ± 8 0.00001 Nfix nuclear factor I/X 780 ± 22 723 ± 31 779 ± 24 761 ± 42 915 ± 51 0.00848 Ntrk2 neurotrophic tyrosine kinase, receptor, type 2 37 ± 3 41 ± 4 38 ± 4 39 ± 4 56 ± 4 0.00319 Pabpc1 poly(A) binding protein, cytoplasmic 1 3309 ± 90 3222 ± 30 3274 ± 58 3309 ± 49 3529 ± 58 0.00520 Picalm phosphatidylinositol binding clathrin assembly protein 1458 ± 18 1528 ± 31 1470 ± 19 1505 ± 23 1591 ± 26 0.00153 Pla2g4a phospholipase A2, group IVA (cytosolic, calcium-dependent) 98 ± 5 97 ± 7 101 ± 6 103 ± 4 122 ± 5 0.00526 Pmp22 peripheral myelin protein 22 698 ± 23 721 ± 20 688 ± 14 705 ± 12 787 ± 24 0.00551 Ppap2b ER transmembrane protein Dri 42 1282 ± 60 1279 ± 56 1343 ± 79 1354 ± 81 1579 ± 91 0.03202 Prdx1 peroxiredoxin 1 2619 ± 35 2521 ± 81 2581 ± 67 2567 ± 76 2893 ± 60 0.00064 Prnp prion protein 12022 ± 378 12242 ± 318 12429 ± 253 12377 ± 189 13207 ± 246 0.03027 Psme1 protease (prosome, macropain) 28 subunit, alpha 810 ± 20 869 ± 28 875 ± 36 830 ± 30 999 ± 27 0.00007 Rbm3 RNA binding motif (RNP1, RRM) protein 3 832 ± 20 776 ± 30 801 ± 17 748 ± 14 948 ± 34 0.00001 Rgs3 regulator of G-protein signalling 3 362 ± 14 370 ± 9 365 ± 7 367 ± 12 402 ± 10 0.03767 Rnase4 ribonuclease, RNase A family 4 1518 ± 32 1530 ± 32 1552 ± 33 1521 ± 34 1663 ± 40 0.01395 Rpl13a ribosomal protein L13A 4201 ± 72 4225 ± 138 4279 ± 49 4085 ± 94 4511 ± 116 0.05087

Page 16 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Rpl4 ribosomal protein L4 4353 ± 103 4340 ± 62 4379 ± 75 4358 ± 49 4636 ± 95 0.04322 Rpl7 ribosomal protein L7 6430 ± 66 6383 ± 62 6551 ± 84 6388 ± 127 6883 ± 153 0.01012 Rps17 ribosomal protein S17 8502 ± 161 8728 ± 111 8680 ± 130 8732 ± 127 9345 ± 171 0.00100 Rps24 ribosomal protein S24 6092 ± 109 6158 ± 98 6241 ± 95 6243 ± 128 6699 ± 203 0.02137 Rps25 ribosomal protein s25 1494 ± 37 1453 ± 40 1531 ± 45 1500 ± 34 1636 ± 41 0.01596 Rps27 ribosomal protein S27 8538 ± 48 8797 ± 221 8793 ± 111 8895 ± 120 9466 ± 247 0.00713 Rps29 ribosomal protein S29 14380 ± 595 14588 ± 560 13919 ± 345 14659 ± 339 15927 ± 495 0.03753 Rps6ka1 ribosomal protein S6 kinase polypeptide 1 115 ± 4 120 ± 8 129 ± 12 124 ± 9 153 ± 8 0.01721 RT1-Bb RT1 class II, locus Bb 39 ± 3 48 ± 8 43 ± 6 56 ± 6 129 ± 9 0.00000 Ryr2 2, cardiac 113 ± 10 96 ± 8 111 ± 5 114 ± 11 144 ± 10 0.00693 Scap2 src family associated phosphoprotein 2 269 ± 12 279 ± 9 280 ± 6 288 ± 16 344 ± 11 0.00007 Serping1 serine (or cysteine) proteinase inhibitor, clade G (C1 inhibitor), member 1, (angioede 129 ± 6 116 ± 7 132 ± 7 139 ± 7 214 ± 10 0.00000 Slc6a6 solute carrier family 6 (neurotransmitter transporter, taurine), member 6 178 ± 6 183 ± 10 199 ± 18 186 ± 16 243 ± 15 0.00673 St14 suppression of tumorigenicity 14 51 ± 4 56 ± 5 59 ± 3 59 ± 5 76 ± 4 0.00159 Syn3 synapsin III 779 ± 24 809 ± 27 810 ± 21 786 ± 37 890 ± 22 0.01738 Syngr2 Synaptogyrin 2 146 ± 8 137 ± 7 148 ± 4 151 ± 7 177 ± 7 0.00067 Tep1 telomerase associated protein 1 155 ± 8 171 ± 9 170 ± 6 169 ± 10 194 ± 7 0.01222 Tgfb2 Transforming growth factor, beta 2 165 ± 7 164 ± 7 175 ± 7 157 ± 5 193 ± 9 0.00858 Tgfbr1 transforming growth factor, beta receptor 1 652 ± 32 637 ± 37 689 ± 18 669 ± 19 774 ± 25 0.00249 Tnxa tenascin XA 148 ± 6 155 ± 7 153 ± 5 159 ± 9 183 ± 7 0.00541 Treh trehalase (brush-border membrane glycoprotein) 872 ± 74 811 ± 72 885 ± 63 888 ± 60 1156 ± 91 0.01308 Vim 461 ± 25 527 ± 37 507 ± 20 528 ± 17 668 ± 28 0.00001 Vkorc1 epoxide reductase complex, subunit 1 536 ± 14 533 ± 15 564 ± 11 530 ± 16 590 ± 12 0.00801 Late - Downregulated Accn1 amiloride-sensitive cation channel 1, neuronal (degenerin) 242 ± 10 250 ± 9 237 ± 11 247 ± 14 212 ± 8 0.04972 Amph1 amphiphysin 1 525 ± 11 519 ± 9 524 ± 15 523 ± 8 480 ± 11 0.01066 Asns asparagine synthetase 881 ± 21 867 ± 16 895 ± 21 886 ± 16 809 ± 20 0.01058 Atp1a1 ATPase, Na+/K+ transporting, alpha 1 polypeptide 2092 ± 33 2155 ± 53 2181 ± 69 2174 ± 59 1914 ± 59 0.00398 Atp6v1b2 ATPase, H+ transporting, V1 subunit B, isoform 2 3391 ± 73 3319 ± 83 3283 ± 63 3264 ± 108 2929 ± 42 0.00038 Atxn10 ataxin 10 homolog () 2745 ± 73 2752 ± 69 2720 ± 71 2753 ± 40 2513 ± 45 0.00893 Birc2 baculoviral IAP repeat-containing 2 632 ± 18 610 ± 11 618 ± 13 639 ± 25 569 ± 14 0.02276 Bmsc-UbP bone marrow stromal cell-derived ubiquitin-like protein 831 ± 27 818 ± 13 847 ± 22 870 ± 24 772 ± 12 0.00794 Cacna2d3 , voltage-dependent, alpha 2/delta 3 subunit 1547 ± 38 1556 ± 39 1642 ± 48 1593 ± 45 1441 ± 32 0.00627 Calm3 calmodulin 3 2560 ± 35 2641 ± 37 2607 ± 36 2586 ± 71 2397 ± 55 0.00536

Page 17 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Camk1g calcium/calmodulin-dependent protein kinase I gamma 99 ± 3 98 ± 3 105 ± 5 98 ± 2 87 ± 5 0.02950 Cask calcium/calmodulin-dependent serine protein kinase 40 ± 3 46 ± 3 47 ± 5 45 ± 2 35 ± 2 0.03112 Ckmt1 creatine kinase, mitochondrial 1, ubiquitous 1997 ± 87 1982 ± 56 1877 ± 38 1964 ± 79 1743 ± 35 0.01090 Clcn4-2 putative chloride channel (similar to Mm Clcn4-2) 283 ± 10 298 ± 6 285 ± 9 287 ± 11 247 ± 9 0.00188 Clstn3 calsyntenin 3 600 ± 51 677 ± 30 629 ± 23 638 ± 41 539 ± 16 0.03254 Crabp1 cellular retinoic acid binding protein I 142 ± 6 130 ± 6 121 ± 4 132 ± 6 106 ± 7 0.00296 Csnk1d casein kinase 1, delta 392 ± 11 398 ± 6 396 ± 7 404 ± 8 369 ± 7 0.02350 Dkk3 dickkopf homolog 3 (Xenopus laevis) 2231 ± 52 2241 ± 52 2186 ± 32 2267 ± 50 2051 ± 57 0.01834 Dncic1 , cytoplasmic, intermediate chain 1 2250 ± 33 2217 ± 68 2220 ± 45 2197 ± 85 1969 ± 50 0.00361 Dscam Down syndrome 193 ± 4 195 ± 6 193 ± 9 192 ± 7 167 ± 7 0.01130 Egr4 early growth response 4 260 ± 17 258 ± 21 241 ± 10 268 ± 13 208 ± 10 0.01877 Eif2b5 eukaryotic translation initiation factor 2B, subunit 5 epsilon 247 ± 6 236 ± 4 238 ± 3 244 ± 5 221 ± 6 0.00188 Enth Enthoprotin 628 ± 24 630 ± 20 650 ± 10 652 ± 15 585 ± 17 0.04637 Gabbr1 gamma-aminobutyric acid (GABA) B receptor 1 1524 ± 65 1633 ± 51 1626 ± 55 1613 ± 52 1441 ± 32 0.02265 Ghitm growth hormone inducible transmembrane protein 3497 ± 47 3467 ± 80 3540 ± 72 3648 ± 153 3249 ± 88 0.04026 Glrb glycine receptor, beta subunit 818 ± 20 810 ± 17 817 ± 22 806 ± 21 734 ± 22 0.01547 Glrx1 glutaredoxin 1 (thioltransferase) 1152 ± 33 1130 ± 29 1142 ± 27 1152 ± 23 1026 ± 38 0.01953 Gnaz guanine nucleotide binding protein, alpha z subunit 264 ± 7 267 ± 11 267 ± 9 267 ± 10 225 ± 6 0.00061 Gnpat glyceronephosphate O-acyltransferase 548 ± 7 549 ± 13 536 ± 9 533 ± 22 498 ± 9 0.01981 Got1 glutamate oxaloacetate transaminase 1 2831 ± 99 2782 ± 62 2801 ± 42 2851 ± 77 2598 ± 51 0.04629 Hagh hydroxyacyl glutathione hydrolase 1076 ± 18 1074 ± 20 1090 ± 18 1088 ± 17 1017 ± 16 0.01665 Hapln1 hyaluronan and proteoglycan link protein 1 282 ± 12 276 ± 9 266 ± 13 275 ± 10 233 ± 8 0.00669 Hmgcr 3-hydroxy-3-methylglutaryl-Coenzyme A reductase 322 ± 14 318 ± 13 310 ± 15 340 ± 12 279 ± 10 0.01434 Htr2c 5-hydroxytryptamine (serotonin) receptor 2C 245 ± 9 274 ± 16 264 ± 16 267 ± 16 216 ± 11 0.01968 Ier5 immediate early response 5 989 ± 54 888 ± 32 968 ± 23 949 ± 25 779 ± 29 0.00021 Inexa , alpha 2922 ± 82 2981 ± 90 3002 ± 86 2920 ± 77 2681 ± 78 0.03371 Ireb2 iron responsive element binding protein 2 257 ± 14 270 ± 5 273 ± 9 263 ± 11 212 ± 7 0.00004 Kcnab1 potassium voltage-gated channel, shaker-related subfamily, beta member 1 1028 ± 28 1055 ± 31 1010 ± 19 1026 ± 53 883 ± 20 0.00093 Kcnf1 Potassium voltage-gated channel, subfamily F, member 1 464 ± 22 427 ± 8 434 ± 19 433 ± 13 380 ± 20 0.01992 Kcnmb4 potassium large conductance calcium-activated channel, subfamily M, beta member 1140 ± 43 1119 ± 29 1058 ± 30 1125 ± 15 1002 ± 23 0.00452 Kns2 kinesin 2 1669 ± 54 1722 ± 29 1638 ± 30 1711 ± 37 1464 ± 48 0.00021 LOC246768 cytosolic leucine-rich protein 587 ± 8 584 ± 11 566 ± 16 575 ± 18 537 ± 9 0.03005 LOC287429 similar to hypothetical protein MGC14151 1762 ± 38 1703 ± 36 1734 ± 33 1701 ± 33 1600 ± 31 0.00906 LOC293508 similar to protein kinase, cAMP dependent, catalytic, beta; cAMP-dependent protein 608 ± 30 575 ± 32 606 ± 7 614 ± 16 482 ± 27 0.00107

Page 18 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA LOC303514 similar to RIKEN cDNA 4121402D02 446 ± 13 423 ± 13 410 ± 11 428 ± 19 369 ± 11 0.00124 LOC305434 similar to hypothetical protein FLJ31564 957 ± 23 926 ± 24 950 ± 23 953 ± 15 862 ± 17 0.00326 LOC363662 similar to breast carcinoma amplified sequence 3; GAOB1 170 ± 7 175 ± 7 161 ± 6 169 ± 12 145 ± 6 0.03274 LOC64201 2-oxoglutarate carrier 1975 ± 54 1975 ± 31 1897 ± 57 1953 ± 40 1757 ± 41 0.00246 Mapk9 mitogen-activated protein kinase 9 619 ± 19 608 ± 11 615 ± 16 622 ± 8 551 ± 16 0.00349 MGC94628 similar to alpha-4 chain (Alpha-tubulin 4) 3342 ± 99 3263 ± 60 3180 ± 81 3231 ± 67 2981 ± 93 0.02953 Mipp65 MIPP65 protein 1172 ± 20 1206 ± 27 1209 ± 31 1221 ± 20 1125 ± 20 0.02535 Mor1 malate dehydrogenase, mitochondrial 2793 ± 54 2939 ± 43 2885 ± 50 2937 ± 71 2630 ± 56 0.00039 Msra Methionine sulfoxide reductase A 260 ± 9 266 ± 10 269 ± 6 278 ± 9 240 ± 7 0.01373 Mtpn myotrophin 916 ± 32 942 ± 30 914 ± 26 982 ± 31 847 ± 29 0.02657 Mycn V-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian) 80 ± 6 79 ± 7 85 ± 4 80 ± 6 62 ± 4 0.02720 Nfyc nuclear transcription factor-Y gamma 358 ± 11 346 ± 8 362 ± 10 347 ± 10 322 ± 9 0.02835 Nlgn3 neuroligin 3 250 ± 15 242 ± 12 218 ± 12 236 ± 13 184 ± 15 0.00684 Nolc1 nucleolar and coiled-body phosphoprotein 1 577 ± 19 569 ± 20 588 ± 14 572 ± 23 500 ± 12 0.00330 Nov nephroblastoma overexpressed gene 3681 ± 154 3877 ± 95 3728 ± 73 3782 ± 87 3454 ± 102 0.05220 Nsf N-ethylmaleimide sensitive fusion protein 3894 ± 140 3964 ± 51 3844 ± 85 3984 ± 104 3569 ± 76 0.01025 Nufip1 nuclear fragile X mental retardation protein interacting protein 1 177 ± 4 177 ± 4 184 ± 9 176 ± 6 161 ± 4 0.04512 Pak2 p21 (CDKN1A)-activated kinase 2 301 ± 5 297 ± 7 287 ± 7 297 ± 5 276 ± 8 0.05266 Pcmt1 protein-L-isoaspartate (D-aspartate) O-methyltransferase 1 2099 ± 45 2205 ± 54 2109 ± 46 2215 ± 66 1970 ± 54 0.01036 Pde1a phosphodiesterase 1A, calmodulin-dependent 427 ± 22 446 ± 16 419 ± 11 440 ± 12 372 ± 14 0.00461 Phtf1 putative homeodomain transcription factor 1 548 ± 12 532 ± 12 519 ± 12 532 ± 12 495 ± 14 0.03264 Pip5k2b phosphatidylinositol-4-phosphate 5-kinase, type II, beta 132 ± 7 137 ± 6 130 ± 5 137 ± 7 115 ± 5 0.04472 Ppm2c protein phosphatase 2C, magnesium-dependent, catalytic subunit 480 ± 10 463 ± 15 466 ± 8 469 ± 7 429 ± 12 0.01401 Prkar1a Protein kinase, cAMP dependent regulatory, type I, alpha 2285 ± 56 2214 ± 39 2150 ± 32 2183 ± 46 1982 ± 37 0.00006 Prkar2b protein kinase, cAMP dependent regulatory, type II beta 664 ± 26 625 ± 15 647 ± 17 636 ± 27 579 ± 12 0.02527 Prps1 phosphoribosyl pyrophosphate synthetase 1 1220 ± 43 1254 ± 21 1276 ± 33 1222 ± 24 1096 ± 41 0.00362 Rab11b RAB11B, member RAS oncogene family 1370 ± 25 1388 ± 28 1357 ± 24 1409 ± 30 1255 ± 31 0.00163 Rab2 RAB2, member RAS oncogene family 3384 ± 51 3405 ± 51 3468 ± 54 3429 ± 46 3205 ± 59 0.00558 Rab3a RAB3A, member RAS oncogene family 2962 ± 71 2945 ± 37 2992 ± 68 3011 ± 74 2688 ± 76 0.00516 Rab3d RAB3D, member RAS oncogene family 180 ± 13 188 ± 18 194 ± 9 188 ± 9 152 ± 6 0.04391 rELO2 ELOVL family member 6, elongation of long chain fatty acids (yeast) 725 ± 20 722 ± 29 679 ± 15 727 ± 27 641 ± 14 0.01321 Rem2 rad and gem related GTP binding protein 2 228 ± 9 228 ± 7 229 ± 8 221 ± 15 196 ± 7 0.04415 Rgc32 response gene to complement 32 1861 ± 45 1791 ± 46 1829 ± 46 1807 ± 33 1689 ± 33 0.02696 Rgs4 regulator of G-protein signaling 4 908 ± 101 800 ± 50 861 ± 72 884 ± 49 658 ± 25 0.02704

Page 19 of 20 Supplemental Table A ARGs grouped by age-course and direction of change

Symbol Name 3 months 6 months 9 months 12 months 23 months ANOVA Rgs7 regulator of G-protein signaling 7 1726 ± 26 1653 ± 32 1688 ± 31 1718 ± 36 1589 ± 23 0.00616 Scn2b sodium channel, voltage-gated, type II, beta polypeptide 345 ± 29 308 ± 16 321 ± 10 315 ± 9 270 ± 15 0.03454 Sdc2 syndecan 2 324 ± 12 333 ± 6 323 ± 7 331 ± 5 301 ± 6 0.01634 Sh3gl2 SH3 domain protein 2A 583 ± 18 602 ± 21 586 ± 7 572 ± 22 512 ± 15 0.00312 Slc11a2 solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2 224 ± 14 209 ± 12 211 ± 11 225 ± 14 178 ± 5 0.01624 Slc17a6 solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), mem 746 ± 40 684 ± 34 662 ± 33 684 ± 35 566 ± 39 0.01378 Sstr2 somatostatin receptor 2 439 ± 37 419 ± 11 433 ± 16 440 ± 16 359 ± 18 0.02646 Stmn4 stathmin-like 4 2508 ± 86 2390 ± 77 2513 ± 62 2508 ± 83 2174 ± 64 0.00306 Stxbp1 syntaxin binding protein 1 632 ± 30 630 ± 22 677 ± 30 639 ± 31 533 ± 38 0.02226 Svop SV2 related protein 743 ± 15 757 ± 9 746 ± 33 730 ± 18 650 ± 15 0.00057 Syn1 synapsin I 2472 ± 72 2438 ± 103 2583 ± 69 2423 ± 72 2159 ± 72 0.00309 Syngr1 synaptogyrin 1 145 ± 10 150 ± 11 165 ± 9 154 ± 6 126 ± 7 0.02481 Syt4 synaptotagmin 4 1271 ± 44 1267 ± 38 1194 ± 29 1328 ± 62 1104 ± 29 0.00147 Tceb1 transcription elongation factor B (SIII), polypeptide 1 2522 ± 82 2411 ± 69 2435 ± 51 2488 ± 90 2200 ± 59 0.01000 Tcp1 t-complex protein 1 2768 ± 37 2817 ± 33 2883 ± 39 2831 ± 43 2654 ± 42 0.00113 Thy1 thymus cell antigen 1, theta 3425 ± 48 3473 ± 62 3562 ± 41 3535 ± 57 3258 ± 49 0.00051 Tubb3 tubulin, beta 3 1693 ± 38 1668 ± 51 1699 ± 34 1661 ± 47 1552 ± 36 0.04666 Uae1 UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase 385 ± 10 391 ± 9 375 ± 15 390 ± 9 350 ± 8 0.02581 Wdr7 WD repeat domain 7 468 ± 19 496 ± 17 476 ± 9 484 ± 18 418 ± 15 0.00641 Zfp238 zinc finger protein 238 1985 ± 68 2022 ± 95 1924 ± 46 1977 ± 44 1650 ± 69 0.00081

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