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Varna Medical Forum

Caloric restriction mimetics as a therapeutic approach to metabolic syndrome

Klementina Moneva-Marinova, Stefka Valcheva-Kuzmanova


Caloric restriction is a reduction in caloric intake without reaching a state of malnutrition, and it affects multiple cellular signaling pathways. Experimental data shows that this leads to an increase in longevity or in maintaining a healthy state for an extended period in both invertebrates and vertebrates, including mammals. Certain food compounds or drugs possess the ability to replicate these effects through shared mechanisms; they are known as caloric restriction mimetics (CRM). What they have in common is the ability to induce autophagy by stimulating deacetylation of cellular proteins. In addition, they modulate energy metabolism and reduce oxidative stress.

The current review aims to explore mechanisms and potential outcomes of CRM utilization in addressing metabolic syndrome, with an emphasis on polyphenols and metformin. Their influence on carbohydrate and lipid metabolism, their antioxidant and anti-inflammatory actions, as well as their modulation of gut microbiota emphasize their suitability for managing metabolic syndrome. These effects are at least partially mediated by the same cellular signaling pathways that are activated by caloric restriction, such as adenosine monophosphate-activated protein kinase, mammalian target of rapamycin (mTOR), sirtuins, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1ɑ), and many others, participating in complex interactions.

The data suggests that CRM is an innovative approach in the prevention and therapy of age-related and non-communicable diseases, showcasing significant potential for targeting metabolic syndrome.


polyphenols; sirtuins; autophagy; adenosine monophosphate-activated protein kinase

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