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A new review highlights chalcones, plant-derived compounds, as emerging geroprotective agents that could mimic caloric restriction and activate cellular renewal mechanisms like autophagy.
The Discovery:
Researchers from the University of Graz and collaborators reveal that chalcones, particularly 4,4’-dimethoxychalcone (4,4’-DMC) and 3,4-dimethoxychalcone (3,4-DMC), extend lifespan and protect against age-related diseases in multiple model organisms. Their unique ability to activate autophagy and modulate cellular stress pathways positions them as potential natural caloric restriction mimetics.
The Science:
4,4’-DMC promotes longevity by inducing autophagy through inhibition of GATA transcription factors, which normally repress this self-cleaning process.
It extends lifespan in yeast, nematodes, and flies, protects heart tissue in mice, and reduces senescent cells, acting as a senolytic.
3,4-DMC activates a different route, stimulating TFEB and TFE3, transcription factors that promote lysosomal biogenesis and autophagy.
Both chalcones show neuroprotective, cardioprotective, and anti-inflammatory effects, improving resilience against aging-associated diseases such as Parkinson’s and cardiovascular conditions.
Other chalcones, like hydroxysafflor yellow A and licochalcone A, further demonstrate benefits in neuroprotection, photoaging, and obesity, often through AMPK activation and autophagy induction.
Your Action:
Include polyphenol-rich foods such as fruits, vegetables, and teas in your daily diet, as many contain flavonoids and chalcone-like compounds. While clinical trials are limited, this natural family of molecules may support healthy cellular function and longevity. Supporting autophagy naturally through intermittent fasting, exercise, and plant-based nutrition aligns with these same mechanisms.
Bottom Line:
Chalcones represent a promising class of natural molecules capable of promoting longevity through autophagy and cellular renewal.
Source:
The geroprotective potential of chalcones, Nature Communications, Didac Carmona-Gutierrez et al., University of Graz and collaborators. Published: September 9, 2025
https://doi.org/10.1038/s41467-025-64167-7
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