Topical and systemic skin aging interventions: Evidence, pitfalls and perspectives

Skin aging is a complex, multifactorial process driven by intrinsic biological factors and extrinsic environmental influences, with ultraviolet radiation playing a central role in accelerating structural and functional skin deterioration. A wide range of topical and systemic interventions have been proposed to prevent or reverse visible signs of skin aging. This review provides a critical evaluation of current skin aging interventions, including antioxidants, hormonal therapies, retinoids, hydrators such as hyaluronic acid, collagen peptides, and emerging senescence-targeting agents. Distinct from prior reviews, this work integrates both a pharmaceutical perspective, focusing on physicochemical properties, formulation stability, and dermal or oral bioavailability of active ingredients, and a methodological assessment of clinical evidence. While several skin aging interventions have been described to show benefits, their clinical effectiveness is often constrained by poor absorption, chemical instability, irritation, or limited mechanistic validation. The existing literature is characterized by small sample sizes, short study durations, subjective outcome measures, lack of appropriate controls, and frequent industry sponsorship, all of which limit the reliability and generalizability of reported outcomes. Retinoids remain the most consistently supported intervention, though tolerability issues persist, whereas evidence for antioxidants, hormonal therapies, hydrators and collagen peptides remains inconclusive. Overall, this review highlights a substantial gap between commercial claims and robust clinical evidence, underscoring the need for large-scale, well-controlled, independent trials with standardized, objective endpoints to establish safe, effective, and evidence-based strategies for healthy skin aging.