{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:47:48Z","timestamp":1782712068467,"version":"3.54.5"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Skin aging is characterized by progressive decline in dermal fibroblast function, marked by reduced extracellular matrix (ECM) synthesis, accelerated ECM degradation, diminished repair capacity, and activation of the senescence-associated secretory phenotype (SASP). Recent studies demonstrate that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), critically regulate this process through two primary mechanisms. First, ncRNAs exert direct regulation, including miRNA-mediated RNA-RNA targeting and lncRNA\/circRNA-mediated direct binding to proteins or DNA\/chromatin. Second, certain lncRNAs and circRNAs act as competing endogenous RNAs (ceRNAs) by sequestering miRNAs, thereby derepressing miRNA-targeted genes. This review systematically outlines the dual regulatory roles of miRNAs, lncRNAs, and circRNAs in dermal fibroblast senescence, summarizes the ceRNA network features in replicative aging, photoaging, and stress-induced premature senescence, and highlights advances and experimental strategies for validating direct regulation. We also note current limitations, including imbalanced research focus on regulatory modes, unclear functions of emerging ncRNAs such as PIWI-interacting RNAs (piRNAs) and small nucleolar RNAs (snoRNAs), and insufficient characterization of fibroblast subpopulation heterogeneity. Future work should integrate single-cell and spatial omics to deepen mechanistic insights and develop ncRNA-based targeted delivery and precision anti-aging interventions.<\/jats:p>","DOI":"10.3389\/fcell.2026.1874939","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:39:20Z","timestamp":1782711560000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual modes of action: direct regulation and ceRNA-mediated mechanisms of ncRNAs in dermal fibroblast senescence"],"prefix":"10.3389","volume":"14","author":[{"given":"Juanlie","family":"Luo","sequence":"first","affiliation":[{"name":"School of Pharmacy, Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabao","family":"Ma","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Tian","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenling","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meizhen","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojiao","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingtong","family":"Lan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e2206732","DOI":"10.1002\/advs.202206732","article-title":"CircTmeff1 promotes muscle atrophy by interacting with TDP-43 and encoding A novel TMEFF1-339aa protein","volume":"10","author":"Chen","year":"2023","journal-title":"Adv. Sci. (Weinh)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e14123","DOI":"10.1111\/acel.14123","article-title":"METTL14 affects UVB-Induced human dermal fibroblasts photoaging via miR-100-3p biogenesis in an m(6)A-dependent manner","volume":"23","author":"Chen","year":"2024","journal-title":"Aging Cell."},{"key":"B3","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1038\/s41467-022-28106-0","article-title":"Parallel functional assessment of m(6)A sites in human endodermal differentiation with base editor screens","volume":"13","author":"Cheng","year":"2022","journal-title":"Nat. Commun."},{"key":"B4","doi-asserted-by":"publisher","first-page":"3018","DOI":"10.1021\/acs.jproteome.1c00074","article-title":"Protein-DNA\/RNA interactions: an overview of investigation methods in the -Omics era","volume":"20","author":"Cozzolino","year":"2021","journal-title":"J. Proteome Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"bbaf432","DOI":"10.1093\/bib\/bbaf432","article-title":"LncPTPred: predicting lncRNA-protein interaction based on crosslinking and immunoprecipitation (CLIP-Seq) data","volume":"26","author":"Das","year":"2025","journal-title":"Brief. Bioinform"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3681","DOI":"10.2147\/ccid.S570073","article-title":"Epigenetic clocks in skin aging: from exposome drivers to biomarkers and therapeutic interventions","volume":"18","author":"Dela","year":"2025","journal-title":"Clin. Cosmet. Investig. Dermatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/j.molcel.2014.03.045","article-title":"Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance","volume":"54","author":"Denzler","year":"2014","journal-title":"Mol. Cell."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1007\/s43630-025-00773-0","article-title":"Unraveling biomolecular interactions: a comprehensive review of the electromobility shift assay","volume":"24","author":"Donga","year":"2025","journal-title":"Photochem Photobiol. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.1007\/s11357-024-01399-3","article-title":"Divergent regulation of long non-coding RNAs H19 and PURPL affects cell senescence in human dermal fibroblasts","volume":"47","author":"Frediani","year":"2025","journal-title":"Geroscience"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1111\/php.13801","article-title":"Long non-coding RNA H19-Overexpressing exosomes ameliorate UVB-induced photoaging by upregulating SIRT1 Via sponging miR-138","volume":"99","author":"Gao","year":"2023","journal-title":"Photochem Photobiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12964-023-01451-3","article-title":"Exosomes in skin photoaging: biological functions and therapeutic opportunity","volume":"22","author":"Hajialiasgary Najafabadi","year":"2024","journal-title":"Cell. Commun. Signal"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1577783","DOI":"10.3389\/fimmu.2025.1577783","article-title":"METTL3-mediated m6A modification regulates D-galactose-induced skin fibroblast senescence through miR-208a-5p","volume":"16","author":"Huang","year":"2025","journal-title":"Front. Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1146\/annurev-biochem-060614-034258","article-title":"PIWI-interacting RNA: its biogenesis and functions","volume":"84","author":"Iwasaki","year":"2015","journal-title":"Annu. Rev. Biochem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1303151","DOI":"10.3389\/fphys.2023.1303151","article-title":"LncRNA-miRNA-mRNA regulatory networks in skin aging and therapeutic potentials","volume":"14","author":"Kim","year":"2023","journal-title":"Front. Physiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2062384","DOI":"10.1155\/2017\/2062384","article-title":"Long noncoding RNAs and RNA-binding proteins in oxidative stress, cellular senescence, and age-related diseases","volume":"2017","author":"Kim","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"13673","DOI":"10.3390\/ijms222413673","article-title":"nc886, a non-coding RNA, is a new biomarker and epigenetic mediator of cellular senescence in fibroblasts","volume":"22","author":"Kim","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"25342","DOI":"10.18632\/aging.203750","article-title":"Protective effects of galangin against H(2)O(2)\/UVB-induced dermal fibroblast collagen degradation via hsa-microRNA-4535-mediated TGF\u03b2\/Smad signaling","volume":"13","author":"Lee","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2570","DOI":"10.1016\/j.jid.2022.03.032","article-title":"miR-10a, miR-30c, and miR-451a encapsulated in small extracellular vesicles are prosenescence factors in human dermal fibroblasts","volume":"142","author":"Lee","year":"2022","journal-title":"J. Investig. Dermatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2408","DOI":"10.1016\/j.celrep.2017.08.041","article-title":"Long noncoding RNA PURPL suppresses basal p53 levels and promotes tumorigenicity in colorectal cancer","volume":"20","author":"Li","year":"2017","journal-title":"Cell. Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e70052","DOI":"10.1111\/phpp.70052","article-title":"Ultraviolet-B irradiation induces miR-663a and miR-4706 accelerated photoaging by targeting sirtuin 6 in human dermal fibroblasts","volume":"41","author":"Li","year":"2025","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"B21","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1186\/s13287-025-04451-x","article-title":"Extracellular vesicle-derived lncRNA VIM-AS1 promotes diabetic wound healing by promoting glycolysis and alleviating cellular senescence","volume":"16","author":"Liang","year":"2025","journal-title":"Stem Cell. Res. Ther."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1111\/jocd.13760","article-title":"Predicting miRNA-lncRNA-mRNA network in ultraviolet A-induced human skin photoaging","volume":"20","author":"Lin","year":"2021","journal-title":"J. Cosmet. Dermatol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e70049","DOI":"10.1111\/acel.70049","article-title":"Mechanistic insights into 5'-tiRNA-His-GTG mediated activation of the JNK pathway in skin photoaging","volume":"24","author":"Liu","year":"2025","journal-title":"Aging Cell."},{"key":"B24","doi-asserted-by":"publisher","first-page":"104895","DOI":"10.1016\/j.jbc.2023.104895","article-title":"PCSK9 inhibition interrupts the cross-talk between keratinocytes and macrophages and prevents UVB-Induced skin damage","volume":"299","author":"Luan","year":"2023","journal-title":"J. Biol. Chem."},{"key":"B25","doi-asserted-by":"publisher","first-page":"843","DOI":"10.3892\/etm.2021.10275","article-title":"Long non-coding RNA TPT1-AS1 alleviates cell injury and promotes the production of extracellular matrix by targeting the microRNA-324-5p\/CDK16 axis in human dermal fibroblasts after thermal injury","volume":"22","author":"Luo","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e3488","DOI":"10.21769\/BioProtoc.3488","article-title":"Ribonucleoprotein immunoprecipitation (RIP) analysis","volume":"10","author":"Martindale","year":"2020","journal-title":"Bio Protoc."},{"key":"B27","doi-asserted-by":"publisher","first-page":"10214","DOI":"10.1038\/s41598-023-37207-9","article-title":"Resistance training rejuvenates aging skin by reducing circulating inflammatory factors and enhancing dermal extracellular matrices","volume":"13","author":"Nishikori","year":"2023","journal-title":"Sci. Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"431","DOI":"10.2217\/epi-2022-0016","article-title":"Advanced glycation end products alter the m(6)A-modified RNA profiles in human dermal fibroblasts","volume":"14","author":"Ouyang","year":"2022","journal-title":"Epigenomics"},{"key":"B29","doi-asserted-by":"publisher","first-page":"140","DOI":"10.21873\/invivo.12685","article-title":"Transgenic immortalization of human dermal fibroblasts mediated through the MicroRNA\/SIRT1 pathway","volume":"36","author":"Promjantuek","year":"2022","journal-title":"Vivo"},{"key":"B30","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1111\/phpp.12887","article-title":"CircRNA-406918 enhances the degradation of advanced glycation end products in photoaged human dermal fibroblasts via targeting cathepsin D","volume":"39","author":"Qu","year":"2023","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1016\/j.jid.2023.02.028","article-title":"Matrix Metalloproteinase-1 expression in fibroblasts accelerates dermal aging and promotes papilloma development in mouse skin","volume":"143","author":"Quan","year":"2023","journal-title":"J. Investig. Dermatol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1007\/s00439-023-02588-4","article-title":"Non-coding RNAs as skin disease biomarkers, molecular signatures, and therapeutic targets","volume":"143","author":"Roso-Mares","year":"2024","journal-title":"Hum. Genet."},{"key":"B33","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s10522-022-09966-x","article-title":"Non-coding RNAs in photoaging-related mechanisms: a new paradigm in skin health","volume":"23","author":"Soheilifar","year":"2022","journal-title":"Biogerontology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.diff.2021.04.002","article-title":"CircAMD1 regulates proliferation and collagen synthesis via sponging miR-27a-3p in P63-mutant human dermal fibroblasts","volume":"119","author":"Su","year":"2021","journal-title":"Differentiation"},{"key":"B35","doi-asserted-by":"publisher","first-page":"110327","DOI":"10.1016\/j.cellsig.2022.110327","article-title":"Anti-senescent effects of long non-coding RNA H19 on human dermal fibroblast cells through impairing microRNA-296-5p-dependent inhibition of IGF2","volume":"94","author":"Tang","year":"2022","journal-title":"Cell. Signal"},{"key":"B36","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1007\/s10495-023-01834-4","article-title":"LncRNA PVT1 delays skin photoaging by sequestering miR-551b-3p to release AQP3 expression via ceRNA mechanism","volume":"28","author":"Tang","year":"2023","journal-title":"Apoptosis"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e13915","DOI":"10.1111\/acel.13915","article-title":"Transcriptomes of human primary skin fibroblasts of healthy individuals reveal age-associated mRNAs and long noncoding RNAs","volume":"22","author":"Tsitsipatis","year":"2023","journal-title":"Aging Cell."},{"key":"B38","doi-asserted-by":"publisher","first-page":"3604","DOI":"10.3390\/ijms24043604","article-title":"Optimization of biotinylated RNA or DNA pull-down assays for detection of binding proteins: examples of IRP1, IRP2, HuR, AUF1, and Nrf2","volume":"24","author":"Tsuji","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1038\/s41580-024-00727-x","article-title":"The senescence-associated secretory phenotype and its physiological and pathological implications","volume":"25","author":"Wang","year":"","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"101103","DOI":"10.1016\/j.mtbio.2024.101103","article-title":"Olea europaea leaf exosome-like nanovesicles encapsulated in a hyaluronic acid\/tannic acid hydrogel dressing with dual \u201cdefense-repair\u201d effects for treating skin photoaging","volume":"26","author":"Wang","year":"","journal-title":"Mater Today Bio"},{"key":"B41","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/j.tips.2025.06.007","article-title":"Structure-function-guided drug development efforts to target lncRNAs","volume":"46","author":"Watmuff","year":"2025","journal-title":"Trends Pharmacol. Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ncrna.2025.07.004","article-title":"5'tiRNA-Glu-TTC targets TRPV3 and activates the PI3K\/AKT signaling pathway to modulate skin photoaging","volume":"15","author":"Xu","year":"2025","journal-title":"Noncoding RNA Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1111\/phpp.12827","article-title":"Bone marrow mesenchymal stem cell-derived exosome miR-29b-3p alleviates UV irradiation-induced photoaging in skin fibroblast","volume":"39","author":"Yan","year":"2023","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"B44","doi-asserted-by":"publisher","first-page":"101548","DOI":"10.1016\/j.tice.2021.101548","article-title":"miR-506-3p regulates TGF- 1 and affects dermal fibroblast proliferation, migration and collagen formation after thermal injury","volume":"72","author":"Yang","year":"2021","journal-title":"Tissue Cell."},{"key":"B45","doi-asserted-by":"publisher","first-page":"jcs261930","DOI":"10.1242\/jcs.261930","article-title":"2'-O-ribose methylation levels of ribosomal RNA distinguish different types of growth arrest in human dermal fibroblasts","volume":"137","author":"Yang","year":"2024","journal-title":"J. Cell. Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1111\/php.14015","article-title":"Expression profiles and functional analysis of transfer RNA-Derived small RNAs (tsRNAs) in photoaged human dermal fibroblasts","volume":"101","author":"Yao","year":"2025","journal-title":"Photochem Photobiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e14358","DOI":"10.1111\/acel.14358","article-title":"Mapping epidermal and dermal cellular senescence in human skin aging","volume":"24","author":"Yu","year":"2025","journal-title":"Aging Cell."},{"key":"B48","doi-asserted-by":"publisher","first-page":"15390","DOI":"10.3390\/ijms232315390","article-title":"Circ_0011129 encapsulated by the small extracellular vesicles derived from human stem cells ameliorate skin photoaging","volume":"23","author":"Zhang","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"e14054","DOI":"10.1111\/acel.14054","article-title":"Aging in the dermis: fibroblast senescence and its significance","volume":"23","author":"Zhang","year":"","journal-title":"Aging Cell."},{"key":"B50","doi-asserted-by":"publisher","first-page":"7677","DOI":"10.3390\/ijms25147677","article-title":"LincRNA-EPS promotes proliferation of aged dermal fibroblast by inducing CCND1","volume":"25","author":"Zhang","year":"","journal-title":"Int. J. Mol. Sci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"6821","DOI":"10.3390\/ijms25136821","article-title":"miR-146a decreases inflammation and ROS production in aged dermal fibroblasts","volume":"25","author":"Zhang","year":"","journal-title":"Int. J. Mol. Sci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1627472","DOI":"10.3389\/fgene.2025.1627472","article-title":"3D-cultured hADSCs-derived exosomes deliver circ_0011129 to synergistically attenuate skin photoaging","volume":"16","author":"Zhang","year":"2025","journal-title":"Front. Genet."},{"key":"B53","doi-asserted-by":"publisher","first-page":"112022","DOI":"10.1016\/j.mad.2024.112022","article-title":"Aberrant expression of messenger and small noncoding RNAomes in aged skin of rats","volume":"223","author":"Zhao","year":"2025","journal-title":"Mech. Ageing Dev."},{"key":"B54","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1186\/s12951-022-01499-2","article-title":"Small extracellular vesicles derived from dermal fibroblasts promote fibroblast activity and skin development through carrying miR-218 and ITGBL1","volume":"20","author":"Zou","year":"2022","journal-title":"J. Nanobiotechnology"},{"key":"B55","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.ijbiomac.2022.12.029","article-title":"Circ004463 promotes fibroblast proliferation and collagen I synthesis by sponging miR-23b and regulating CADM3\/MAP4K4 via activation of AKT\/ERK pathways","volume":"226","author":"Zou","year":"2023","journal-title":"Int. J. Biol. Macromol."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1874939\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:39:21Z","timestamp":1782711561000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1874939\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":55,"alternative-id":["10.3389\/fcell.2026.1874939"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1874939","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]},"article-number":"1874939"}}