Skin aging, a multifactorial and progressive process, is heavily influenced by extrinsic factors such as ultraviolet B (UVB) radiation and oxidative stress caused by hydrogen peroxide (H₂O₂). These stressors accelerate the accumulation of senescent cells and reactive oxygen species (ROS), which contribute to degradation of dermal components like collagen and elastin. Central to regulating aging is SIRT1, a NAD⁺-dependent deacetylase, known for its anti-inflammatory and antioxidant roles. However, with aging, SIRT1 levels diminish, largely due to increased autophagy-mediated degradation.
Polydeoxyribonucleotide (PDRN), a DNA-derived compound known for its regenerative and anti-inflammatory properties, was hypothesized to prevent SIRT1 degradation, thus combating aging at a cellular level. This study explored whether PDRN could serve as a protective agent against skin aging by modulating SIRT1 expression and autophagy pathways.
Methods
To investigate the anti-aging effects of PDRN, researchers used both in vitro (HaCaT and human dermal fibroblast cells exposed to UVB or H₂O₂) and in vivo (UVB-irradiated mouse models) approaches. PDRN treatment was administered post-exposure, and assays were conducted to assess cell viability, apoptosis, senescence, wound healing, gene expression, and protein levels. Techniques included flow cytometry, RT-PCR, immunofluorescence, and western blotting.
Key Findings
- Enhanced Cell Survival:
PDRN significantly improved cell viability and reduced apoptosis in UVB- and H₂O₂-damaged keratinocytes. - Reduced Senescence:
PDRN-treated cells showed a decrease in senescence-associated β-galactosidase staining, suggesting reduced cellular aging. - Inhibited Stress Granule Formation:
PDRN attenuated cytoplasmic stress granule accumulation of SIRT1, preserving its function. - Autophagy Modulation:
PDRN reduced nuclear autophagy by decreasing LC3 and p62 localization, preventing SIRT1 degradation. - Restored SIRT1 Expression:
Treatment restored SIRT1 levels in both cytoplasm and nucleus, promoting antioxidant and anti-aging responses. - Downregulation of Senescence Markers:
PDRN suppressed p53, p21, and p16 expression—key markers of aging. - MMP-1 Inhibition:
Matrix metalloproteinase-1, responsible for collagen breakdown, was significantly reduced after PDRN treatment. - In Vivo Efficacy:
In UVB-irradiated mice, PDRN treatment restored normal skin architecture and thickness, confirming anti-aging benefits.
This study uncovers a novel mechanism by which PDRN exerts anti-aging effects—by inhibiting nuclear autophagy and preventing SIRT1 degradation. The dual action of protecting nuclear integrity and preserving critical anti-aging proteins makes PDRN a promising candidate for future cosmeceutical applications targeting photoaging and oxidative skin damage. Its ability to modulate gene and protein expression in both cell cultures and animal models marks a significant step toward the development of effective, biologically active anti-aging skincare ingredients. Further clinical studies are warranted to validate its potential in human topical formulations.
