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.

The skin is continuously exposed to environmental changes, rendering it vulnerable to damage from external stressors that contribute to premature skin aging. This study aims to explore skin longevity pathways stimulated by a rose extract (RE) derived from petals. Human keratinocytes treated with RE exhibited a significant increase in NRF2 (NF-E2-related factor 2; ≈2–4% of induction) and LAMP2A (Lysosome-Associated Membrane Protein 2A; ≈6–12% of induction) levels. The presence of RE significantly mitigated the increase in carbonylation levels (≈34–37% of protection) and the number of labeled P16^INK4A cells (≈60–72% of protection), associated with proliferation arrest, both induced by exposure to BAP (Benzo[a]pyrene) coupled with UV-A (Ultraviolet A) irradiation. The beneficial effects mediated by RE were inhibited by Compound C, a specific AMPK inhibitor (AMP-activated protein kinase). The involvement of the AMPK pathway in mediating the beneficial effects of RE has been confirmed by assessing its activation through the evaluation of its phosphorylation state which was significantly elevated in the presence of RE compared to the stress condition. In conclusion, the activation of the AMPK pathway enhances antioxidant defenses and promotes autophagy. This dual action, mediated by RE, helps protect skin cells from oxidative damage and senescence while maintaining proteostasis, skin integrity, and cellular proliferation under pollution-induced stress (BAP + UV-A). These findings highlight the potential in mitigating age-related skin changes through the modulation of longevity pathways.