What question did this study set out to answer?

To assess the role of dermal fibroblast dysfunction in skin aging and evaluate topical therapies that target these mechanisms.

June 20, 2026Open Access

Mechanistic Review of Topical Therapies Targeting Dermal Fibroblasts in Skin Aging and Rejuvenation

Key Points

To assess the role of dermal fibroblast dysfunction in skin aging and evaluate topical therapies that target these mechanisms.
Narrative review of literature on fibroblast-related molecular pathways and topical interventions for skin aging.
Focus on specific aging phenotypes like wrinkles, sagging, scarring, and photoaging.
UVB radiation leads to wrinkle formation via activation of collagen-degrading enzymes.
Sagging is due to UVA damage affecting connective tissues and fat distribution.
Topical agents like retinol and niacinamide improve collagen synthesis and protect against oxidative damage.

Abstract

ABSTRACT Background Skin aging appears in multiple forms, including wrinkles, sagging, scarring, atrophy, and photoaging. Although each phenotype has distinct biological features, all are rooted in dermal fibroblast dysfunction. This review examines the molecular pathways underlying these conditions and evaluates topical interventions designed to restore skin integrity. Aims To assess how dermal fibroblast dysfunction contributes to different skin aging phenotypes and to evaluate topical therapies targeting the underlying molecular mechanisms. Methods A narrative review of the literature was conducted focusing on fibroblast‐related molecular pathways and topical interventions used for skin aging and rejuvenation. Results UVB radiation contributes to wrinkle formation by activating collagen‐degrading enzymes in the upper dermis, whereas sagging results from UVA‐induced damage to deeper connective tissues and altered fat distribution. Scarring is characterized by excessive fibroblast activation and extracellular matrix overproduction, while atrophy develops through fibroblast senescence and loss of structural support. Photoaging involves oxidative stress and elastin disorganization caused by chronic ultraviolet exposure. Topical agents including retinol, niacinamide, caffeine, asiaticoside, and related compounds stimulate collagen synthesis, reduce matrix degradation, and protect fibroblasts from oxidative damage. Unlike previous reviews that examine skin aging as a single process, this review compares distinct aging phenotypes through the common framework of fibroblast dysfunction and their associated molecular targets. Conclusions Dermal fibroblast dysfunction is a central mechanism underlying multiple forms of skin aging. Targeting fibroblast‐related pathways with topical therapies may address the biological causes of wrinkles, sagging, scarring, atrophy, and photoaging, supporting more personalized and effective skin rejuvenation strategies.

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