A discovery platform for the identification of caloric restriction mimetics with broad health-improving effects.
Cardioprotection
TFE3
TFEB
flavonoid
immunosurveillance
Journal
Autophagy
ISSN: 1554-8635
Titre abrégé: Autophagy
Pays: United States
ID NLM: 101265188
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
pubmed:
7
11
2019
medline:
25
11
2020
entrez:
7
11
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31690168
doi: 10.1080/15548627.2019.1688984
pmc: PMC6984457
doi:
Substances chimiques
Transcription Factors
0
Acetyl Coenzyme A
72-89-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
188-189Références
EMBO Mol Med. 2019 Nov 7;11(11):e10469
pubmed: 31609086