Andrea Cavagnino, Gayané Azadiguian, Lionel Breton, Martin A. Baraibar, Annie Black
Environmental stressors such as pollution and ultraviolet (UV) radiation contribute significantly to skin aging and skin photo-aging, alongside intrinsic chronological factors. Recent insights into longevity science have emphasized mitochondrial health, proteostasis, and autophagic balance as critical processes for maintaining skin integrity. This study investigates the protective potential of a natural product, Rose-derived PolyDeoxyRiboNucleotide (PDRN), against mitochondrial dysfunction and dysregulated autophagy in primary human keratinocytes subjected to environmental stress (benzo-a-pyrene and UV-A). PDRN was evaluated at 0.1%, 0.05%, and 0.01% concentrations. Mitochondrial function was assessed through membrane polarization, ATP/ADP ratio, Complex V (CV-ATP5A) levels, and citrate synthase levels. LAMP2A levels were quantified to evaluate the autophagic pathway. Complementary analyses were performed on ex vivo human skin explants, evaluating oxidative protein damage (carbonylation), Collagen I/III integrity, MMP1 and IL1a levels, and mitophagy markers (PINK1, PARK2). The results confirm significant protection of mitochondrial function, attenuation of oxidative stress, and modulation of autophagy-related pathways by PDRN across all models tested. These findings underscore the capacity of this novel natural product, a plant-derived PDRN, to mitigate environmental skin aging (and photo-aging) through mitochondrial maintenance and proteostasis regulation, positioning Rose-PDRN as a key active ingredient for dermocosmetic formulations targeting skin longevity biomarkers.