Caloric Restriction Mimetics in Nutrition and Clinical Trials

Abstract

The human diet and dietary patterns are closely linked to the health status. High-calorie Western-style diets have increasingly come under scrutiny as their caloric load and composition contribute to the development of non-communicable diseases, such as diabetes, cancer, obesity, and cardiovascular disorders. On the other hand, calorie-reduced and health-promoting diets have shown promising results in maintaining health and reducing disease burden throughout aging. More recently, pharmacological Caloric Restriction Mimetics (CRMs) have gained interest of the public and scientific community as promising candidates that mimic some of the myriad of effects induced by caloric restriction. Importantly, many of the CRM candidates activate autophagy, prolong life- and healthspan in model organisms and ameliorate diverse disease symptoms without the need to cut calories. Among others, glycolytic inhibitors (e.g., D-allulose, D-glucosamine), hydroxycitric acid, NAD+ precursors, polyamines (e.g., spermidine), polyphenols (e.g., resveratrol, dimethoxychalcones, curcumin, EGCG, quercetin) and salicylic acid qualify as CRM candidates, which are naturally available via foods and beverages. However, it is yet unclear how these bioactive substances contribute to the benefits of healthy diets. In this review, we thus discuss dietary sources, availability and intake levels of dietary CRMs. Finally, since translational research on CRMs has entered the clinical stage, we provide a summary of their effects in clinical trials.

Slt2 Is Required to Activate ER-Stress-Protective Mechanisms through TORC1 Inhibition and Hexosamine Pathway Activation

“…In addition, GlcN causes transcriptional reprogramming [102] and represses the respiration rate (QO 2 ), even more rapidly than glucose [103], which contributes to reducing energy supply. Consistent with all of this, GlcN has been reported to increase the life span of C. elegans and aging mice by mimicking a low-carbohydrate diet [104] and it has been proposed as a promising candidate for pharmacological caloric restriction mimetics [105]. Thus, the results of our study showing that the ATP balance in GlcN-treated and -untreated control cells is rather similar suggests that compensatory mechanisms operate to reduce the demand of ATP when the HBP flux is overloaded, which is consistent with a downregulation of N-glycosylated proteins after GlcN addition to the culture medium.…”

d-Allulose Improves Endurance and Recovery from Exhaustion in Male C57BL/6J Mice

“…Owing to its chronic effect on body weight and insulin resistance, D-allulose has been proposed as a caloric restriction mimetic [44][45][46]. We suggest D-allulose as an exercise mimetic, which shares common features with caloric restriction mimetics.…”

Protective Effects of Curcumin in Cardiovascular Diseases—Impact on Oxidative Stress and Mitochondria

“…Thus, CR counteracts the detrimental effects of permanent mTORC1 activation, which is observed in many metabolic and cardiovascular disorders [171]. Several natural substances including curcumin have been shown to evoke similar effects as CR and, therefore, have been termed caloric restriction mimetics [172,173]. Curcumin is a specific CBP/p300 inhibitor [174] and can also induce autophagy.…”