Targeting Circadian Rhythm for the Regulation of Skin Collagen Metabolism

📖 Top 30% JournalJan 13, 2026Journal of cosmetic dermatology

Using the Body’s Internal Clock to Control Skin Collagen Metabolism

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Abstract

Collagen metabolism in human skin fibroblasts is regulated by circadian rhythms.

Collagen assembly genes peak during the day, while genes for synthesis, secretion, and degradation peak at night.
Baicalin enhances collagen assembly during the daytime, whereas palmitoyl tripeptide-1 (PT-1) promotes collagen synthesis at night.
A combination of daytime baicalin and nighttime PT-1 increased collagen fiber density in mice.
In a clinical trial with 30 female participants, significant improvements were observed in skin luminance (+16.29%), nasolabial fold depth (-36.35%), and firmness (+24.35%).
Time-coordinated application of these compounds may synergistically optimize collagen metabolism and improve overall skin quality.

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BACKGROUND: Collagen is essential for maintaining skin structure and function, and the circadian rhythm is known to regulate a wide range of physiological processes.

AIMS: To investigate whether collagen metabolism in human skin fibroblasts exhibits circadian regulation, and to evaluate whether the time-coordinated application of baicalin at daytime and palmitoyl tripeptide-1 (PT-1) at nighttime synergistically promotes collagen fiber formation and improves overall skin quality.

METHODS: A circadian-synchronized human skin fibroblast model was established. The expression of collagen metabolism-related genes was analyzed using qPCR and immunofluorescence. Subsequently, an 8-week topical application study was conducted in mice using a regimen of daytime baicalin and nighttime PT-1. Finally, a clinical trial involving 30 female participants was conducted, employing the same time-coordinated application scheme.

RESULTS: Fibroblasts exhibited opposing day-night rhythms: genes for collagen assembly (e.g., LOX) peaked during the day, while those involved in synthesis/secretion (e.g., Sec61a2, Mia3, Pde4d, Vps33b) and degradation (e.g., CTSK, MMP1) peaked at night. Time phase-dependent interventions showed baicalin enhanced daytime assembly, while PT-1 boosted nighttime synthesis. In mice, a timed day-night combination therapy increased collagen fiber density. Clinical trial (n = 30) confirmed the efficacy, showing significant improvements in skin luminance (+16.29%), nasolabial fold depth (-36.35%), and firmness (R2: +24.35%).

CONCLUSIONS: Collagen metabolism is regulated by circadian rhythms. Chronomodulated baicalin and PT-1 application synergistically optimize collagen metabolism and improve skin quality.

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