Mechanisms and early efficacy data of caloric restriction and caloric restriction mimetics in neurodegenerative disease

[Display omitted] •Caloric Restriction Mimetics (CRMs) are the chemicals that mimic the effects of Caloric Restriction (CR).•CRMs mimic CR effects via the mTOR, insulin, and sirtuin pathways, aiding cellular health and longevity.•CRMs such as resveratrol, metformin, and rapamycin enhance autophagy, benefiting Alzheimer's and Parkinson's diseases.•Clinical trials on CRMs have shown mixed results, but ongoing studies hold promise for improved outcomes.•Reconsidering the trial parameters, inclusion criteria, and dosages can optimize CRMs efficacy and synergistic mechanisms. Neurodegenerative disorders (NDDs) have been prevalent for more than a decade, and the number of individuals affected per year has increased exponentially. Among these NDDs, Alzheimer’s disease, which causes extreme cognitive impairment, and Parkinson’s disease, characterized by impairments in motor activity, are the most prevalent. While few treatments are available for clinical practice, they have minimal effects on reversing the neurodegeneration associated with these debilitating diseases. Lifestyle modifications and dietary choices are emerging and promising approaches to combat these disorders. Of the lifestyle changes that one could adopt, a major habit is caloric restriction. Caloric restriction (CR) is a lifestyle modification in which the amount of calories ingested is reduced to a significant amount without resulting in malnutrition. However, maintaining such a lifestyle is challenging. As alternatives, certain compounds have been recognized to mimic the effects produced by CR. These compounds are called caloric restriction mimetics (CRMs). Among these compounds, some have been designated established CRMs, namely, resveratrol, metformin, and rapamycin, whereas several other candidates are termed potential CRMs because of a lack of conclusive evidence of their effects. The potential CRMs discussed in this review are quercetin, chrysin, astragalin, apigenin, curcumin, epigallocatechin-3-gallate, and NAD+ precursors. This review aims to provide an overview of these CRMs’ effectiveness in preventing neurodegenerative disorders associated with aging. Moreover, we highlight the clinical relevance of these compounds by discussing in detail the results of clinical trials on them.