Anesthetic-induced epigenetic alterations: mechanisms and long-term clinical implications

This review explores how anesthetic agents influence epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA expression, and their lasting clinical effects. Common anesthetics, including propofol, isoflurane, sevoflurane, and local or regional agents, trigger epigenetic alterations. Preclinical research, especially in developing and aging brains, ties these changes to neurodevelopmental delays, cognitive decline, and shifts in immune and metabolic processes. While clinical studies are ongoing, accumulating evidence reveals that anesthesia triggers both transient and persistent epigenetic modifications, with potential links to postoperative cognitive dysfunction, prolonged inflammation, and altered developmental trajectories. Pediatric and elderly patients show heightened susceptibility due to brain plasticity or diminished resilience. Leveraging epigenetic knowledge could pave the way for tailored anesthesia approaches, reducing long-term risks. Moreover, emerging evidence suggests intergenerational transmission of these epigenetic changes via germline reprogramming, potentially affecting neurodevelopment and disease susceptibility in offspring. Future studies should prioritize large-scale human trials, detailed mechanistic insights, and identification of epigenetic biomarkers to guide safer anesthetic development. This review highlights anesthesia's broader systemic consequences, extending beyond immediate cognitive impacts, and underscores its relevance to personalized medicine.