Dual modes of action: direct regulation and ceRNA-mediated mechanisms of ncRNAs in dermal fibroblast senescence

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.