The flavonoid 4,4'-dimethoxychalcone promotes autophagy-dependent longevity across species.
Aging
/ drug effects
Angelica
/ chemistry
Animals
Autophagy
/ drug effects
Caenorhabditis elegans
/ drug effects
Cation Transport Proteins
/ genetics
Cell Death
/ drug effects
Cell Line
/ drug effects
Drosophila melanogaster
/ drug effects
Flavonoids
/ administration & dosage
GATA Transcription Factors
/ drug effects
Gene Expression Regulation
/ drug effects
Humans
Longevity
/ drug effects
Male
Mechanistic Target of Rapamycin Complex 1
/ metabolism
Medicine, East Asian Traditional
Mice
Mice, Inbred C57BL
Myocardial Ischemia
/ drug therapy
Plant Extracts
/ pharmacology
Saccharomyces cerevisiae
/ drug effects
Saccharomyces cerevisiae Proteins
/ genetics
Signal Transduction
Sirolimus
/ pharmacology
Transcription Factors
/ drug effects
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 02 2019
19 02 2019
Historique:
received:
30
10
2018
accepted:
11
01
2019
entrez:
21
2
2019
pubmed:
21
2
2019
medline:
12
4
2019
Statut:
epublish
Résumé
Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4'-dimethoxychalcone (DMC) as a natural compound with anti-ageing properties. External DMC administration extends the lifespan of yeast, worms and flies, decelerates senescence of human cell cultures, and protects mice from prolonged myocardial ischaemia. Concomitantly, DMC induces autophagy, which is essential for its cytoprotective effects from yeast to mice. This pro-autophagic response induces a conserved systemic change in metabolism, operates independently of TORC1 signalling and depends on specific GATA transcription factors. Notably, we identify DMC in the plant Angelica keiskei koidzumi, to which longevity- and health-promoting effects are ascribed in Asian traditional medicine. In summary, we have identified and mechanistically characterised the conserved longevity-promoting effects of a natural anti-ageing drug.
Identifiants
pubmed: 30783116
doi: 10.1038/s41467-019-08555-w
pii: 10.1038/s41467-019-08555-w
pmc: PMC6381180
doi:
Substances chimiques
Cation Transport Proteins
0
Flavonoids
0
GATA Transcription Factors
0
GLN3 protein, S cerevisiae
0
MEP2 protein, S cerevisiae
0
Plant Extracts
0
Saccharomyces cerevisiae Proteins
0
Transcription Factors
0
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
651Subventions
Organisme : Austrian Science Fund FWF
ID : I 3301
Pays : Austria
Commentaires et corrections
Type : CommentIn
Type : CommentIn
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