Abstract
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.
Highlights
Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases
Epidemiological studies suggest that the regular consumption of polyphenol-rich foods may decrease the risk of many chronic conditions[4], and certain polyphenols—most prominently resveratrol—have been shown to extend life and/or health span in several model organisms ranging from yeast to mice[5]
We found that administration of DMC promotes cytoprotection and autophagy across species and that autophagy induction is required for the beneficial effects of this compound
Summary
D–f Phosphatidylserine externalisation and membrane dysintegrity (d), ROS production (e) and survival (f) of DMC-treated yeast cells (100 μM) at indicated time points of chronological ageing using AnnexinV/PI costaining (d), ***P < 0.001, n = 18, DHE to ethidium conversion, n = 6 (e) and clonogenicity, n = 8 (f) independent biological replicates; P-values represent T, treatment; A, age; T ×A, interaction. Source data for (b, d, e, g, i) are provided as a Source Data file which code for essential components of the autophagic machinery, abolished DMC-mediated lifespan extension in yeast, worms, and flies (Fig. 4, Supplementary Fig. 7a–h). This indicates that autophagy induction is necessary for the beneficial effects of DMC.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
