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Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice
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Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice

Published on: November 27, 2019

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A discovery platform for the identification of caloric restriction mimetics with broad health-improving effects

Oliver Kepp1,2,3, Guo Chen1,2,3,4, Didac Carmona-Gutierrez5

  • 1Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138, Paris, France.

Autophagy
|November 7, 2019
PubMed

Insights

Researchers identified a novel compound, 3,4-dimethoxychalcone (3,4-DC), that mimics caloric restriction benefits. This compound promotes cellular repair and shows potential in protecting the heart and enhancing cancer immunity.

Area of Science:

  • Cellular Biology
  • Aging Research
  • Pharmacology

Background:

  • Organismal aging leads to decreased fitness and increased disease susceptibility.
  • Caloric restriction (CR) and fasting can counteract aging and extend lifespan.
  • Caloric restriction mimetics (CRMs) offer CR benefits without dietary changes, promoting cellular health via increased autophagic flux.

Purpose of the Study:

  • To develop a high-throughput platform for discovering novel CRMs.
  • To identify compounds that imitate the health-promoting effects of caloric restriction.
  • To validate CRM candidates using in vitro and in vivo models.

Main Methods:

  • Utilized systems biology approaches for CRM discovery.
  • Employed in vitro validation and functional tests.
  • Tested candidate compounds in in vivo disease models.

Main Results:

  • Identified 3,4-dimethoxychalcone (3,4-DC) as a novel CRM.
  • 3,4-DC stimulates transcription factor EB (TFEB) and transcription factor E3 (TFE3)-dependent autophagy.
  • Demonstrated cardioprotective effects and enhanced anticancer immunosurveillance of 3,4-DC.

Conclusions:

  • A novel high-throughput platform successfully identified 3,4-DC as a CRM.
  • 3,4-DC promotes autophagy and exhibits therapeutic potential in cardiovascular health and cancer immunotherapy.
Keywords:
CardioprotectionTFE3TFEBflavonoidimmunosurveillance

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