Human photoaging skin models for the efficacy evaluation of anti-aging ingredients: Advances on clinical and ex vivo studies

Solar radiation impacts the skin's biological processes, leading to premature aging. Accurately identifying and evaluating these effects in humans through tissue-based models is essential for advancing anti-aging research and validating cosmetic ingredients claims. However, the existing literature remains highly fragmented, hindering the identification of suitable photoaging skin models and knowledge gaps. This work provides a comprehensive and up-to-date review of human (clinical and ex vivo) photoaging skin models used to assess the anti-aging efficacy of cosmetic ingredients, paving the way for the development of more advanced models for this purpose. A total of 43 studies using human skin (24 clinical and 19 ex vivo studies) were identified and curated. Clinical studies capture integrated physiological responses, in their majority associated with the improvement of clinical manifestations, whereas ex vivo models enable controlled mechanistic assessments of cellular and molecular changes. The key biomarkers evaluated in these studies encompass the main hallmarks of skin aging, including inflammation, oxidative stress, cellular senescence, and structural alterations. In recent years, the assessment of photo-induced alterations in skin fibers and oxidation products has improved considerably due to the advances in the spectroscopic techniques in clinical studies. Despite these advances, variability in exposure conditions, biomarker selection, and phototype representation thwarts deeply cross-study comparisons. Future progress should focus on incorporating a broader range of Fitzpatrick phototypes, optimising irradiation conditions to approximate to the chronic solar exposure and integrating new biomarkers such as advanced glycation end-products and immunosuppressive indicators. The implementation of emerging technologies, such as skin-on-a-chip systems, and microfluidics, could enhance physiological relevance and reproducibility. Overall, this review identifies the key findings, highlighting strengths and limitations of the models, and future priorities towards the development and implementation of accurate human skin models for assessing anti-aging efficacy.