Skin aging is a complex and multifactorial biological process that leads to gradual deterioration in the skin’s structure, function and appearance. Common clinical manifestations include fine lines, wrinkles, dyspigmentation, laxity, and loss of elasticity. This process is influenced by intrinsic (endogenous) factors such as genetics, cellular senescence, and hormonal changes, as well as extrinsic (exogenous) factors including ultraviolet (UV) radiation, environmental pollutants, and mechanical stress. These factors contribute to underlying physiological changes like glycation, oxidative stress, inflammation, impaired DNA repair, and extracellular matrix degradation (Shin et al., 2023; Knaggs et al., 2023).

Topical antiaging treatments have gained significant popularity in clinical dermatology, with retinoids—particularly tretinoin—recognized as the gold standard due to their proven efficacy in reducing fine lines, evening skin tone, promoting collagen synthesis, and increasing epidermal turnover (Milosheska & Roskar, 2022; Sitohang et al., 2022).

Tretinoin, a derivative of vitamin A, penetrates the epidermis and binds to intracellular retinoic acid receptors (RARs). These receptors form heterodimers with retinoid X receptors (RXRs), which then bind to retinoic acid response elements (RAREs) in the DNA of keratinocytes and fibroblasts. This molecular interaction regulates the transcription of various genes responsible for skin remodelling and repair.

Through this RAR–RXR–RARE signalling axis, tretinoin upregulates the expression of genes involved in collagen production, including procollagen I and III, thereby enhancing skin firmness and reducing wrinkles. It also boosts skin regeneration by promoting cellular turnover and supports angiogenesis, which improves oxygen and nutrient delivery to the skin. Simultaneously, tretinoin downregulates processes contributing to photoaging, such as excessive keratinocyte proliferation, matrix metalloproteinases (MMPs) that degrade collagen, pro-inflammatory cytokines like IL-6 and TNF-alpha, and tyrosinase activity, which is involved in melanin synthesis and pigmentation.

The primary target cells of tretinoin are keratinocytes in the epidermis and fibroblasts in the dermis. Keratinocytes influence epidermal thickness and renewal, while fibroblasts are central to extracellular matrix (ECM) maintenance, producing collagen and elastin. By modulating gene expression in both cell types, tretinoin not only stimulates collagen synthesis and inhibits its degradation but also reduces inflammation and pigmentation, making it a fundamental agent in dermatologic anti-aging treatment strategies (Uchida et al., 2003; Mambwe et al., 2025).