Polydeoxyribonucleotides (PDRN), highly purified DNA-derived polymers, were approved by the Italian Medicines Agency (AIFA) in 1994 to treat superficial wounds, skin ulcers, and dystrophic connective tissue disorders. Since then, PDRN have gained considerable attention as regenerative biomaterials. Beyond their established role in wound healing, they have also been approved as dermal fillers in several countries, with growing clinical evidence supporting their benefits for facial skin health. Recent clinical and preclinical studies suggest that PDRN may improve various skin conditions, including wrinkles, dryness, hyperpigmentation, hair loss, and barrier dysfunction. These findings have generated interest in their broader dermatological applications beyond traditional indications. This review aims to explore the therapeutic potential of PDRN for the treatment of skin disorders. We examine the efficacy and safety of PDRN-based drugs and medical devices in dermatology, with a focus on their clinical applications, pharmacological effects, and underlying molecular mechanisms. Given that PDRN consists of over 90% purified DNA, we further examine the biological functions of extracellular DNA (exDNA) and propose potential mechanisms by which PDRN may function as exDNA, beyond its classical action via the A2A receptor pathway. Collectively, current evidence highlights PDRN as safe and effective biopolymers with promising potential as DNA-based therapeutics in dermatology.

Background/Objectives: With the rapid aging of the global population, the interest in therapies for age-related diseases has increased substantially. The skin is particularly important, as aging-related changes are visible and negatively impact quality of life. Therefore, the identification of senotherapeutic candidates that are effective against skin aging is of considerable importance. Given the cost and reproducibility limitations of existing senescence models, this study established three dermal fibroblast senescence models induced by etoposide, hydrogen peroxide, and ultraviolet A, representing intrinsic and extrinsic aging. Furthermore, considering the adverse effects of current photoaging treatments, such as tretinoin and methoxsalen, we investigated the senotherapeutic potential of araliadiol, a plant-derived compound, in these models. Methods: Senescence induction and validation were assessed using trypan blue-based cell counting, senescence-associated β-galactosidase (SA-β-gal) staining, and adenosine triphosphate content assays. The senotherapeutic potential of araliadiol was further evaluated using quantitative reverse transcriptase–polymerase chain reaction, Western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay. Results: Compared with non-senescent fibroblasts, senescent cells exhibited increased SA-β-gal positivity, elevated intracellular reactive oxygen species levels, and upregulated p16 and p21 expression. The senolytic agent ABT-737 selectively induced apoptosis in senescent fibroblasts but not in non-senescent fibroblasts, validating the models. Araliadiol showed no senolytic activity but demonstrated potential senomorphic effects, including reduced expression of senescence-associated secretory phenotype (SASP) genes (IL1β, IL6, IL8, CCL2, and CXCL1) and NF-κB p65 phosphorylation, suppression of MMP-1 (up to 2.35-fold reduction) and MMP-3 (up to 30.53-fold reduction) expression and AP-1 activation, and increased extracellular procollagen type I content (up to 18.35% increase). Conclusions: Araliadiol exerted senomorphic—but not senolytic—effects across three validated dermal fibroblast senescence models, supporting its potential as a natural topical therapeutic agent for mitigating skin aging.

The extract of Scenedesmus deserticola JD052 has been reported to exhibit anti-aging effects on the skin, with research indicating an increase in loliolide, a major active component, through heterotrophic cultivation. In this study, we evaluated the effects of extracts obtained from both photoautotrophic (PE) and heterotrophic (HE) cultures on hair-inductive properties in human dermal papilla (HDP) cells. Biochemical assays demonstrated that both extracts enhanced HDP cell viability and increased the size of three-dimensional dermal papilla (DP) spheres. Notably, the activation of β-catenin, a crucial marker associated with hair growth, was assessed using a luciferase reporter assay, revealing that HE exhibited a significantly higher efficacy than PE. Further analyses indicated that HE promoted the translocation of β-catenin into the nucleus through the phosphorylation and activation of AKT, which also elevated the expression levels of DP signature genes and hair-growth-related autocrine factors. Additionally, conditioned media from HE-treated HDP cells enhanced keratinocyte migration and increased the expression of growth factors, including VEGF and IGF-1. HPLC-MS analysis showed no significant difference in loliolide content; however, specific peaks in HE were identified as pheophorbide A and linolelaidic acid. Thus, HE may enhance hair growth inductivity via AKT/β-catenin signaling.

Excessive accumulation of reactive oxygen species from exogenous and endogenous stressors can cause cellular damage. Chlorella contains diverse bioactive compounds, and violaxanthin, a major carotenoid pigment found in Chlorella sp. HS-V, has been reported to possess anti-inflammatory, anticancer, and antioxidant properties. We investigated the effect of violaxanthin on hydrogen peroxide (H₂O₂)-induced oxidative stress in human keratinocytes. Chlorella sp. HS-V extract significantly restored the H₂O₂-induced decrease in cell viability. Similarly, violaxanthin reduced H₂O₂-induced cytotoxicity and intracellular reactive oxygen species levels, which was associated with the upregulation of antioxidant enzyme expression. Under H₂O₂-induced oxidative stress conditions, violaxanthin may enhance cellular antioxidant defense by promoting nuclear factor erythroid 2-related factor 2 (NRF2) translocation through the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3β (PI3K/AKT/GSK3β) signaling pathway. Additionally, violaxanthin improved H₂O₂-impaired wound healing in HaCaT human keratinocyte cells and reduced senescence-associated beta-galactosidase-positive normal human epidermal keratinocytes. Overall, these findings suggest that violaxanthin may serve as a potential therapeutic agent for mitigating oxidative stress-induced cellular dysfunction.