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

被引：21

作者：

Kepp, Oliver ^{[1
,2
,3
]}

Chen, Guo ^{[1
,2
,3
,4
]}

Carmona-Gutierrez, Didac ^{[5
]}

Madeo, Frank ^{[5
,6
,7
]}

Kroemer, Guido ^{[1
,2
,3
,8
,9
,10
]}

机构：

[1] INSERM, U1138, Ctr Rech Cordeliers, Equipe Labellisee Ligue Canc 11, Paris, France

[2] Gustave Roussy Comprehens Canc Ctr, Metabol & Cell Biol Platforms, Villejuif, France

[3] Univ Paris 05, Sorbonne Paris Cite, Paris, France

[4] Nankai Univ, Coll Life Sci, Tianjin, Peoples R China

[5] Graz Univ, NAWI Graz, Inst Mol Biosci, Graz, Austria

[6] Med Univ Graz, Dept Internal Med, Div Endocrinol & Diabetol, Graz, Austria

[7] BioTechMed Graz, Graz, Austria

[8] Hop Europeen Georges Pompidou, Pole Biol, Paris, France

[9] Chinese Acad Sci, Suzhou Inst Syst Med, Suzhou, Peoples R China

[10] Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Stockholm, Sweden

来源：

AUTOPHAGY | 2020年 / 16卷 / 01期

关键词：

Cardioprotection; flavonoid; immunosurveillance; TFE3; TFEB;

D O I：

10.1080/15548627.2019.1688984

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：188 / 189

页数：2