Journal of Human Growth and Development · Sep 10, 2026
Skin aging and ceramides: molecular alterations and therapeutic strategies for epidermal barrier restoration. A systematic review
By Cavalcanti ASS, da Silva AG, Marques DDS et al.
Introduction: the lipid matrix of the skin stratum corneum, composed of three essential lipid classes, ceramides, cholesterol and free fatty acids organized in highly ordered lamellae, is essential for maintaining the integrity of the cutaneous barrier. In the process of skin aging, progressive alterations in the composition and proportions of ceramide subclasses are reported that directly and indirectly interfere with the functions they perform for cutaneous homeostasis. Objective: to systematically review evidence on stratum corneum ceramide alterations in skin aging, their consequences for barrier function, and the topical interventions investigated to restore their homeostasis. Method: a systematic literature review was performed in PubMed/MEDLINE, Scopus, Web of Science, Embase and Wiley Online Library, covering articles published between January 2016 and January 2026. The descriptors used were Ceramides, Stratum Corneum, Aging, Skin, and Dermatological Agents. Studies in humans and experimental models were included that addressed at least one of the following thematic axes: composition of ceramides in the lipid lamellae of the stratum corneum, alterations of these molecules associated with skin aging and their functional consequences, and dermatological formulations aimed at replacing ceramides in the lamellar matrix. In total, 138 articles were identified, of which 70 were included after screening. Results: the literature indicates that skin aging is associated with progressive changes in the lipid composition of the stratum corneum, including shifts in the proportions of specific ceramide subclasses. Different studies have particularly reported an accumulation of dihydroceramides and a reduction in essential structural ceramides; taken together, these alterations correlate with lamellar disorganization and impaired barrier function, and are also associated with increased transepidermal water loss, xerosis, pruritus, and greater susceptibility to environmental insults.In parallel, evidence from other clinical and experimental studies shows that topical supplementation with ceramides or their precursors can promote the restoration of lipid composition, lamellar organization, and cohesion between the lipid matrix and corneocytes, with a consequent reduction in sensitivity to irritants and allergens. Conclusion: Knowledge of age-dependent lipid composition changes and their correlations with impairment of the protective cutaneous function, and of the results arising from topical supplementation, supports the use of lipids physiologically compatible with the stratum corneum matrix, in adequate proportions and pH between 4.0 and 5.5, as a therapeutic strategy to restore the barrier function in aged skin. Dermatological formulations incorporating ceramides or their precursors, with attention to the solubilization of the active ingredient and the vehicle used, offer concrete therapeutic prospects for the clinical management of symptoms and signs of skin aging. Longitudinal studies with standardized protocols are needed to consolidate therapeutic recommendations and allow personalization of approaches according to the individual lipid profile.