Anti-Aging Efficacy of Low-Molecular-Weight Polydeoxyribonucleotide Derived from Paeonia lactiflora

Polydeoxyribonucleotide (PDRN), a DNA fragment mixture, exerts biological effects via adenosine A2A receptor and salvage pathway activation. Here, <i>Paeonia lactiflora</i>-derived PDRN (Peony PDRN) is proposed as a plant-based alternative to salmon-derived PDRN. While <i>P. lactiflora</i> is known for its medicinal properties, the biological functions of Peony PDRN have not been characterized. To validate and optimize its efficacy, we systematically compared the biological activities of three molecular weight groups of Peony PDRN (high, medium, and low) using in vitro assays and clinical studies. The low-molecular-weight fraction (Low-Peony PDRN) markedly enhanced skin cell proliferation and migration, upregulated extracellular matrix-related genes (<i>COL1A1</i>, <i>COL5A1</i>, <i>ELN</i>, and <i>FBN1</i>), and promoted keratinocyte differentiation and epidermal barrier formation by increasing <i>COL7A1</i>, <i>IVL</i>, <i>FLG</i>, and <i>OCLN</i> expression. It also reduced reactive oxygen species levels and suppressed key inflammatory mediators. Clinically, topical application of Low-Peony PDRN for 2 weeks markedly reduced transepidermal water loss in a sodium lauryl sulfate-induced skin damage model, enhancing barrier recovery (<i>n</i> = 10). Periorbital skin elasticity improved after 4 weeks of treatment (Approval No. Intertek IRB-202505-HR(1)-0001, 20 June 2025). These results indicate that Low-Peony PDRN is a promising plant-derived biomaterial of pharmacological and cosmetic significance, with potential to address skin aging.