Title : Clinical study combining confocal microscopy and bioinformatics demonstrates the ability of a regenerative miniprotein to reverse markers of epidermal senescence
Abstract:
Introduction: Epidermal aging is characterized by a progressive decline in keratinocyte and cell density, structural disorganization, and the accumulation of senescent cells. Advanced imaging technologies have identified quantifiable biomarkers associated with this process, including intercellular spacing and alterations in cellular morphology. The present study aimed to validate imaging based biomarkers through bioinformatics as robust and sensitive tools for assessing the efficacy of a regenerative miniprotein designed to target cellular senescence.
Methods: We conducted a 56-day, randomized, placebo-controlled 'split-face' clinical trial involving more than 50 women aged from 40 to 60 years. In vivo confocal microscopy, was used to capture high-resolution images of facial skin, focusing on the stratum granulosum (SG) and the stratum spinosum (SS). Several metrics were measured, including the density and count of normal and senescent cells, cell circularity, as well as the thickness of the intercellular space. Statistical analyses were performed using linear mixed model (LMM) to assess correlations between age related changes and treatment effects.
Results: A significant correlation was observed between aging and increased intercellular spacing, as alongside a reduction in the density of normal keratinocytes within the SG layer. Total cell circularity emerged as a reliable biomarker of epidermal aging. Treatment with the miniprotein resulted in statistically significant improvements in all parameters. As early as D14, reduction in the density and count of senescent cells were observed accompanied by improvement of cellular circularity, By day 56, intercellular gaps in the SG layer were significantly reduced. Within the SS layer, the miniprotein induced a significant and sustained reduction in both the density and number of senescent cells from D14 to D56.
Discussion/Conclusions: The study demonstrates that quantitative metrics derived from in vivo confocal microscopy provide robust biomarkers for evaluating epidermal aging and treatment response. The tested miniprotein showed significant modulation of cellular and structural markers associated with epidermal senescence, suggesting senolytic and/or senomorphic activity. In addition, the miniprotein improved epidermal cohesion as shown by the reduction of intercellular space. These findings support the relevance of this miniprotein in anti-aging dermatological strategies and validate advanced imaging combined with bioinformatics as a powerful platform for assessing skin regenerative treatments.
