Research Progress in Skin Anti-Aging Drugs Based on Core Pathological Drivers.

BACKGROUND: Skin aging is driven by multiple interconnected pathological processes. However, existing evidence remains fragmented across studies of individual mechanisms and compounds, hindering the discovery of novel targets and the repurposing of established drug targets.This review systematically summarizes the fundamental mechanisms and categorizes current antiaging pharmacological strategies corresponding to these mechanisms, aiming to provide a theoretical framework for future drug development and clinical translation. METHODS: PubMed/MEDLINE and ClinicalTrials.gov were searched from inception through June 2026 using core and compound-specific strategies. Eligible reports evaluated defined interventions for intrinsic skin aging or photoaging and reported efficacy, mechanistic, or safety outcomes. Of 7,973 records identified, 675 duplicates and 6,933 records were removed during AI-assisted prescreening, leaving 365 for human screening. The final synthesis included 91 reports covering 47 intervention classes. Data were extracted into nine prespecified fields, classified using a five-level evidence hierarchy, and synthesized narratively because heterogeneity precluded meta-analysis. RESULTS AND CONCLUSION: Current evidence indicates that oxidative stress functions not only as an initiating trigger, but a parallel amplifier, and a downstream consequence within the bidirectional feedback loops of mitochondrial dysfunction and other aging mechanisms. It connects multiple aging-related pathways as a central hub. Interventions targeting oxidative stress have demonstrated promising outcomes in both in vitro and in vivo studies. Accordingly, we propose an evidence-stratified, mechanism-to-translation framework integrating skin organoid models, nanoparticle-based delivery systems, and artificial intelligence-driven target screening to guide multimechanism intervention strategies, facilitate targeted drug development, and accelerate precision clinical translation.