INNOVATIVE AGENTS OF ANTI-AGE PHARMACOTHERAPY IN DERMATOLOGY
DOI:
https://doi.org/10.11603/mcch.2410-681X.2026.i2.16002Keywords:
skin aging; circadian rhythms; exosomes; melatonin; rapamycin; neocollagenesis; anti- age; Skin Longevity.Abstract
Introduction. Modern dermatocosmetology is shifting from the aesthetic correction of external signs of aging toward the deep management of the skin's biological age (Skin Longevity). Melatonin is known to be a key regulator of circadian rhythms, and the disruption of the cellular "biological clock" is a primary cause of reduced skin regenerative potential. The drug rapamycin, through its unique ability to influence the mTORC1 pathway, enables the clearance of "biological debris" from cells (autophagy) and counteracts the state of inflammaging (chronic low-grade inflammation). Exosomes represent the most promising method of cell-free therapy, providing targeted delivery of genetic information to "reprogram" aged cells toward rejuvenation. The aim of the study was to analyze the role of circadian oscillators in the mechanisms of skin aging and to substantiate the effectiveness of multimodal regeneration strategies based on the use of exosome therapy, chronobiotic support with melatonin, and metabolic modulation of the mTORC1 pathway with rapamycin. Materials and Methods. A critical analysis and systematization of scientific data regarding the molecular mechanisms of skin aging were conducted, along with a comparative analysis of clinical and experimental research results in accordance with the study's objective. Relevant sources were identified in the PubMed, Scopus, and ClinicalTrials.gov electronic databases using keywords: skin longevity, circadian rhythms, exosomes, mTOR, melatonin. Results and Discussion. It was established that a key mechanism of skin aging is desynchronosis – the disruption of internal "clock" genes (specifically BMAL1 and PER2). This leads to cells losing their ability to repair effectively during sleep. Analysis of melatonin's action showed that it functions not merely as an antioxidant but as a potent chronobiotic. It penetrates the blood-brain barrier and cell membranes, binds to specific receptors, and restores the circadian rhythm of fibroblasts. This stimulates the production of endogenous collagen and elastin, and activates enzymes that protect DNA from ultraviolet damage. Inhibition of the mTORC1 protein complex with low doses of rapamycin triggers the process of autophagy in the skin. This essentially acts as an intracellular "recycling system" that processes damaged proteins and organelles. Consequently, this reduces the number of senescent cells ("zombie cells") that provoke chronic inflammation and destroy the surrounding matrix. The study of exosome impact demonstrated their role as an intelligent delivery system. Exosomes derived from mesenchymal stem cells contain a unique set of miRNAs and growth factors. Upon reaching the deep layers of the dermis, they transmit a "youth signal" to aged fibroblasts, inhibiting the activity of collagen-degrading enzymes and initiating vigorous neocollagenesis. Conclusions. An innovative anti-aging strategy must be comprehensive and aimed at restoring the skin's internal biological rhythms. Melatonin, rapamycin, and exosomes are promising innovative agents in dermatology that require further study regarding their safety and efficacy.
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