A discovery platform for the identification of caloric restriction mimetics with broad health-improving effects
Article 2019 en
Authors
OK
Oliver Kepp
GC
Guo Chen
DC
Didac Carmona‐Gutiérrez
Abstract
1 min read
The age-related decline in organismal fitness results in vulnerability to pathologies and eventual lethal decay. One way to counteract cellular aging and to delay and/or prevent the onset of age-related maladies is the reduction of calorie intake or the institution of fasting regimens. Caloric restriction mimetics (CRMs) have the ability to imitate the health-promoting and lifespan-extending effects of caloric restriction without the need for dietary restriction. CRMs induce an increase in autophagic flux in response to the deacetylation of cellular proteins in the absence of cytotoxicity. Here we report the development of a high-throughput discovery platform for novel CRMs that uses systems biology approaches, in vitro validation and functional tests employing in vivo disease models. This workflow led to the identification of 3,4-dimethoxychalcone (3,4-DC) as a novel CRM that stimulated TFEB (transcription factor EB)- and TFE3 (transcription factor E3)-dependent macroautophagy/autophagy. 3,4-DC showed cardioprotective effects and stimulated anticancer immunosurveillance in the context of immunogenic chemotherapy.
Guo Chen, Wei Xie, Jihoon Nah, Allan Sauvat, Peng Liu, Federico Pietrocola, Valentina Sica, Didac Carmona‐Gutiérrez, Andreas Zimmermann, Tobias Pendl, Jelena Tadić, Martina Bergmann, Sebastian J. Hofer, Lana Domuz, Sylvie Lachkar, Maria Markaki, Nektarios Tavernarakis, Junichi Sadoshima, Frank Madeo, Oliver Kepp, Guido Guido Kroemer
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