# Epigenetic Mechanisms, Assessment and Therapeutics of Epidermal Stem Cells in Skin Aging **Authors:** Jiayu Yang, Mohan Xu, Yiheng Duan, Yuhang Yuan, Jiaming Zhang, Wenqing Jiang PMC · DOI: 10.1155/sci/7575250 · Stem Cells International · 2025-12-18 ## TL;DR This review explores how epigenetic changes affect skin stem cells during aging and how targeting these changes could lead to new anti-aging treatments. ## Contribution The paper provides a comprehensive overview of epigenetic mechanisms in epidermal stem cell aging and emerging therapeutic strategies. ## Key findings - Epigenetic modifications like DNA methylation and histone changes regulate epidermal stem cell function during aging. - Epigenetic clocks such as Horvath’s and VisAgeX offer precise biomarkers for measuring biological age and treatment efficacy. - Targeting epigenetic disruptions presents promising avenues for developing anti-aging dermatological therapies. ## Abstract Skin aging is a multifaceted biological process driven by genetic and environmental factors, in which epidermal stem cells (EpSCs) decrease in number and decline in function. Emerging evidence indicates that epigenetic modifications play a crucial regulatory role in the aging process. Therefore, elucidating the epigenetic mechanisms in aging will provide novel avenues for developing strategies to delay aging. In this review, we explore the epigenetic mechanisms regulating EpSCs function, namely DNA methylation (DNAm), histone modifications, noncoding RNA, and their dysregulation and the resulting series of manifestations during aging. Furthermore, we introduce epigenetic clocks such as Horvath’s and the skin‐specific VisAgeX to quantify these age‐related changes, which provide precise biomarkers of biological age, enabling the assessment of both aging progression and therapeutic outcomes. Finally, we summarize emerging interventions targeting these epigenetic disruptions. Advancing these epigenetic modulations holds significant potential for cutaneous antiaging and fostering innovative dermatological treatments. ## Full-text entities - **Genes:** DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}, IGFBP3 (insulin like growth factor binding protein 3) [NCBI Gene 3486] {aka BP-53, IBP-3, IBP3, IGFBP-3}, SMAD3 (SMAD family member 3) [NCBI Gene 4088] {aka HSPC193, HsT17436, JV15-2, LDS1C, LDS3, MADH3}, PSME4 (proteasome activator subunit 4) [NCBI Gene 23198] {aka Blm10, PA200, hBlm10}, TRAF6 (TNF receptor associated factor 6) [NCBI Gene 7189] {aka MGC:3310, RNF85}, DNMT3L (DNA methyltransferase 3 like) [NCBI Gene 29947], HMGB2 (high mobility group box 2) [NCBI Gene 3148] {aka HMG2}, HMGB1 (high mobility group box 1) [NCBI Gene 3146] {aka HMG-1, HMG1, HMG3, SBP-1}, TSPAN4 (tetraspanin 4) [NCBI Gene 7106] {aka NAG-2, NAG2, TETRASPAN, TM4SF7, TSPAN-4}, MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, WNT5A (Wnt family member 5A) [NCBI Gene 7474] {aka hWNT5A}, SNAI1 (snail family transcriptional repressor 1) [NCBI Gene 6615] {aka SLUGH2, SNA, SNAH, SNAIL, SNAIL1, dJ710H13.1}, PRMT1 (protein arginine methyltransferase 1) [NCBI Gene 3276] {aka ANM1, HCP1, HRMT1L2, IR1B4}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CDKN2B (cyclin dependent kinase inhibitor 2B) [NCBI Gene 1030] {aka CDK4I, INK4B, MTS2, P15, TP15, p15INK4b}, PRRT2 (proline rich transmembrane protein 2) [NCBI Gene 112476] {aka BFIC2, BFIS2, DSPB3, DYT10, EKD1, FICCA}, GLB1 (galactosidase beta 1) [NCBI Gene 2720] {aka EBP, ELNR1, MPS4B}, H4C6 (H4 clustered histone 6) [NCBI Gene 8361] {aka H4, H4/c, H4FC, HIST1H4F}, TET3 (tet methylcytosine dioxygenase 3) [NCBI Gene 200424] {aka BEFAHRS, hCG_40738}, COL17A1 (collagen type XVII alpha 1 chain) [NCBI Gene 1308] {aka BA16H23.2, BP180, BPA-2, BPAG2, ERED, JEB4}, SPRY1 (sprouty RTK signaling antagonist 1) [NCBI Gene 10252] {aka hSPRY1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, LMNB1 (lamin B1) [NCBI Gene 4001] {aka ADLD, LMN, LMN2, LMNB, MCPH26}, SOX5 (SRY-box transcription factor 5) [NCBI Gene 6660] {aka L-SOX5, L-SOX5B, L-SOX5F, LAMSHF}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, TWIST1 (twist family bHLH transcription factor 1) [NCBI Gene 7291] {aka ACS3, BPES2, BPES3, CRS, CRS1, CSO}, SMAD2 (SMAD family member 2) [NCBI Gene 4087] {aka CHTD8, JV18, JV18-1, LDS6, MADH2, MADR2}, PEG3 (paternally expressed 3) [NCBI Gene 5178] {aka PW1, ZKSCAN22, ZNF904, ZSCAN24}, PDE4A (phosphodiesterase 4A) [NCBI Gene 5141] {aka DPDE2, PDE4, PDE46}, TMPO (thymopoietin) [NCBI Gene 7112] {aka CMD1T, LAP2, LEMD4, PRO0868, TP}, CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026] {aka CAP20, CDKN1, CIP1, MDA-6, P21, SDI1}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, IRF4 (interferon regulatory factor 4) [NCBI Gene 3662] {aka IMD131, LSIRF, MUM1, NF-EM5, SHEP8}, IL1R1 (interleukin 1 receptor type 1) [NCBI Gene 3554] {aka CD121A, CRMO3, D2S1473, IL-1R-alpha, IL-1RT1, IL1R}, DNMT3A (DNA methyltransferase 3 alpha) [NCBI Gene 1788] {aka DNMT3A2, HESJAS, M.HsaIIIA, TBRS}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CYBRD1 (cytochrome b reductase 1) [NCBI Gene 79901] {aka CYB561A2, DCYTB, FRRS3}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, LAMB3 (laminin subunit beta 3) [NCBI Gene 3914] {aka AI1A, BM600-125KDA, JEB1A, JEB1B, LAM5, LAMNB1}, TIMP2 (TIMP metallopeptidase inhibitor 2) [NCBI Gene 7077] {aka CSC-21K, DDC8}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312] {aka CLG}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, KRT16 (keratin 16) [NCBI Gene 3868] {aka CK16, FNEPPK, K16, K1CP, KRT16A, NEPPK}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, KRT72 (keratin 72) [NCBI Gene 140807] {aka CK-72, K6IRS2, K6irs, K72, KRT6, KRT6IRS2}, IGFBP7 (insulin like growth factor binding protein 7) [NCBI Gene 3490] {aka AGM, FSTL2, IBP-7, IGFBP-7, IGFBP-7v, IGFBPRP1}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, RAC1 (Rac family small GTPase 1) [NCBI Gene 5879] {aka MIG5, MRD48, Rac-1, TC-25, p21-Rac1}, MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314] {aka CHDS6, MMP-3, SL-1, STMY, STMY1, STR1}, MKI67 (marker of proliferation Ki-67) [NCBI Gene 4288] {aka KIA, MIB-, MIB-1, PPP1R105}, ZEB1 (zinc finger E-box binding homeobox 1) [NCBI Gene 6935] {aka AREB6, BZP, DELTAEF1, FECD6, NIL2A, PPCD3}, MMP14 (matrix metallopeptidase 14) [NCBI Gene 4323] {aka MMP-14, MMP-X1, MT-MMP, MT-MMP 1, MT1-MMP, MT1MMP} - **Diseases:** Hutchinson Gilford Progeria Syndrome (MESH:D011371), mitochondrial complex abnormalities (MESH:C565375), dryness (MESH:D014987), infections (MESH:D007239), DEJ (MESH:D004814), JEB (MESH:D016109), kidney carcinoma (MESH:D007680), tumor (MESH:D009369), water loss (MESH:D000069578), inflammation (MESH:D007249), chronic wounds (MESH:D014947) - **Chemicals:** NADH (MESH:D009243), T3 (MESH:D014284), ROS (MESH:D017382), polyphenols (MESH:D059808), lipid (MESH:D008055), ectoine (MESH:C045628), T4 (MESH:D013974), HE (-), Apremilast (MESH:C505730), curcumin (MESH:D003474), DHM (MESH:C472036), cytosine (MESH:D003596), 5-mC (MESH:D044503), retinoids (MESH:D012176), genistein (MESH:D019833) - **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Bacillus sp. AA (species) [taxon 412897], Aframomum angustifolium (species) [taxon 199615], Mus musculus (house mouse, species) [taxon 10090] - **Cell lines:** HaCaT — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0038) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12767457/full.md ## Figures 2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12767457/full.md ## References 102 references — full list in the complete paper: https://tomesphere.com/paper/PMC12767457/full.md --- Source: https://tomesphere.com/paper/PMC12767457