The Role of Retinoids in Acne Treatment and Anti-Ageing: A Critical Narrative Review of Mechanisms, Clinical Evidence, and Therapeutic Translation

Abstract

Retinoids occupy a singular position in dermatological therapeutics, bridging two of the specialty's most clinically and psychosocially significant indications: acne vulgaris and cutaneous photoageing. Acting principally through nuclear retinoic acid receptors, these vitamin A derivatives normalise follicular keratinisation, exert anti-inflammatory effects, and remodel the dermal extracellular matrix, providing a unifying mechanistic rationale for their use across a remarkably broad therapeutic spectrum. This review synthesises contemporary evidence on the pharmacology, clinical efficacy, and safety of topical and systemic retinoids in acne management, alongside their established and emerging applications in skin rejuvenation. Four generations of topical retinoids, from tretinoin to the receptor-selective fourth-generation agent trifarotene, are appraised with attention to comparative efficacy, tolerability, and the delivery technologies developed to mitigate retinoid dermatitis. Oral isotretinoin remains the most effective intervention for severe, scarring, or treatment-resistant acne, although its use demands rigorous pregnancy prevention measures and continued vigilance regarding mucocutaneous, metabolic, and possible neuropsychiatric sequelae, the latter of which recent large-scale meta-analytical data have helped to put into proportion. In cosmetic dermatology, all-trans retinoic acid is still the reference standard for reversing histological and clinical features of photoageing, while cosmeceutical derivatives such as retinol, retinaldehyde, and hydroxypinacolone retinoate, together with the phytochemical bakuchiol, offer better-tolerated alternatives with more modest but clinically meaningful efficacy. The review also considers the growing evidence base for retinoids in preventing and treating acne scarring, the importance of tailoring regimens for patients with darker skin phototypes, and the formulation innovations, including polymeric emulsions, microencapsulation, and nanocarrier systems, that are reshaping tolerability without compromising efficacy. Taken together, the evidence affirms retinoids as an indispensable, mechanistically coherent therapeutic class whose continued refinement promises to extend their benefit while narrowing the gap between efficacy and adherence.