The ups and downs of caloric restriction and fasting: from molecular effects to clinical application

EMBO Mol Med. 2022 Jan 11;14(1):e14418. doi: 10.15252/emmm.202114418. Epub 2021 Nov 15.

Abstract

Age-associated diseases are rising to pandemic proportions, exposing the need for efficient and low-cost methods to tackle these maladies at symptomatic, behavioral, metabolic, and physiological levels. While nutrition and health are closely intertwined, our limited understanding of how diet precisely influences disease often precludes the medical use of specific dietary interventions. Caloric restriction (CR) has approached clinical application as a powerful, yet simple, dietary modulation that extends both life- and healthspan in model organisms and ameliorates various diseases. However, due to psychological and social-behavioral limitations, CR may be challenging to implement into real life. Thus, CR-mimicking interventions have been developed, including intermittent fasting, time-restricted eating, and macronutrient modulation. Nonetheless, possible side effects of CR and alternatives thereof must be carefully considered. We summarize key concepts and differences in these dietary interventions in humans, discuss their molecular effects, and shed light on advantages and disadvantages.

Keywords: caloric restriction; fasting; healthspan; intermittent fasting; lifespan; time-restricted eating.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Caloric Restriction*
  • Diet
  • Fasting* / physiology
  • Humans