Abstract: Skin aging is characterized by dermal atrophy, degeneration of elastic fibers, collagen depletion, and attenuated epidermal turnover. Photobiomodulation therapy (PBMT), particularly red light irradiation, has demonstrated promising anti-aging potential; however, its underlying molecular mechanisms remain incompletely elucidated. In this study, we established a natural aging mouse model (18～20 months) to investigate the rejuvenating effects and mechanisms of red light treatment with parameter of 630～635 nm, fluence 8 J/cm2, power density 6.67 mW/cm2, 20 min per session for 28 consecutive days. Our results demonstrated that red light significantly increased dermal thickness and enhanced type I collagen deposition in aged mice. Mechanistic investigations revealed that red light promoted collagen synthesis in fibroblasts via activation of the AKT signaling pathway; concurrently, AKT activation stimulated keratinocyte proliferation with elevated Ki67 expression, and differentiation with increased cytokeratin 10 expression, effects that were abrogated by the AKT inhibitor API-2. These findings collectively indicate that red light mediates coordinated dermal-epidermal remodeling through AKT signaling, providing a theoretical foundation for the application of photobiomodulation therapy in the prevention and treatment of skin aging.
Key words: photobiomodulation; red light; skin aging; AKT signaling pathway; collagen; keratinocyte
（Acta Laser Biology Sinica, 2026, 35(2): 179-184）