Miméticos de la Restricción Energética: Un Análisis Comparativo de Agentes Naturales y Sintéticos en la Modulación de la Autofagia

Introduction: Caloric restriction (CR) has been proven effective in extending longevity and preventing age-related diseases. However, its implementation in humans faces challenges, such as adverse effects and low adherence. Caloric restriction mimetics (CRMs) are emerging as promising alternatives, replicating the benefits of CR by modulating key metabolic pathways like AMPK, mTOR, and SIRT1. Method: A narrative review was conducted based on studies from 2004 2004 to October 2024 using key terms related to CR and CRMs. The selection included studies on animal models and humans, evaluating natural agents such as resveratrol and spermidine, and synthetic compounds like metformin and rapamycin. Results: Natural CRMs, such as resveratrol and spermidine, promote autophagy through SIRT1 activation and mTOR regulation, improving cellular homeostasis and reducing chronic inflammation. Synthetic agents, like metformin and rapamycin, induce more potent autophagy, though with associated risks such as immunosuppression. Animal studies show improvements in longevity and metabolic health, while human benefits require further validation. Conclusions: CRMs represent an innovative option to prevent age-related diseases and enhance quality of life. Combining natural and synthetic agents could optimize their effectiveness, but longitudinal studies are essential to ensure their safety and clinical applicability.