Pharmacological potential of calorie restriction mimetics in mitigating brain aging

Quality of life is strongly influenced by brain aging, which is closely associated with neurodegeneration. With brain aging, various changes occur at the cellular, tissue, and organ levels, such as loss of proteostasis; dysregulation of nutrient sensing; abnormalities in the functions of mitochondria; and changes in neurophysiology. These changes also affect cognitive capabilities and result in mild to severe cognitive impairment. The three main mechanisms of brain aging, namely, senescence, inflammation, and oxidative stress, are being investigated in experimental models. Interventions such as caloric restriction, ketone diets, and intermittent fasting have shown the potential for slowing brain aging by modulating nutrition-sensing pathways, which improve metabolic health, decrease oxidative stress, and reduce inflammatory responses. However, noncompliance with these traditional interventions makes them inefficient. To overcome this drawback, caloric restriction mimetics (CRMs), which tend to produce greater effects than traditional methods without affecting dietary intake, are better therapeutic options. This chapter focuses on the transition of CRMs from preclinical to clinical trials in humans.