RNA Regulatory Networks and Skin Longevity: Molecular Mechanisms, Functional Resilience, and Translational Opportunities for Cosmetic Science

RNA Regulatory Networks and Skin Longevity: Molecular Mechanisms, Functional Resilience, and Translational Opportunities for Cosmetic Science An Integrative Critical Review and Proposed Systems Biology Framework Skin aging involves interconnected changes in cellular homeostasis, mitochondrial regulation, inflammatory signaling, extracellular matrix organization, and epidermal barrier function. Although advances in RNA biology and transcriptomics have expanded our understanding of these processes, the relationship between molecular aging signatures and long-term preservation of cutaneous functionality remains incompletely established. This independent critical integrative review examines the roles of messenger RNA, microRNAs, long non-coding RNAs, circular RNAs, and epitranscriptomic mechanisms in biological processes relevant to skin aging. Particular attention is given to cellular senescence, mitochondrial homeostasis, inflammaging, dermal mechanobiology, epidermal barrier resilience, and transcriptomic aging biomarkers. The article proposes the RNA–Skin Longevity Axis (RSLA), a hypothesis-generating systems biology framework connecting RNA regulatory states, cellular homeostasis, tissue functional resilience, and longitudinal skin health. The central research proposition is whether RNA-derived information can provide reproducible explanatory or predictive value for meaningful cutaneous functional outcomes beyond conventional demographic, environmental, and biophysical assessments. The review also discusses RNA-based delivery technologies and RNA-informed cosmetic research while distinguishing molecular feasibility from validated functional efficacy. The RSLA is presented as an unvalidated conceptual framework requiring independent experimental assessment, rather than an established biological pathway or clinically proven longevity intervention. Publication type: Independent Critical Integrative Review and Proposed Conceptual Framework. Peer-review status: Not peer-reviewed. Author: Mohammad Baghaei, PharmD, DBA.