TY - JOUR
T1 - 4,4'Dimethoxychalcone
T2 - a natural flavonoid that promotes health through autophagy-dependent and -independent effects
AU - Zimmermann, Andreas
AU - Kainz, Katharina
AU - Hofer, Sebastian J.
AU - Bauer, Maria A.
AU - Schroeder, Sabrina
AU - Dengjel, Jörn
AU - Pietrocola, Federico
AU - Kepp, Oliver
AU - Ruckenstuhl, Christoph
AU - Eisenberg, Tobias
AU - Sigrist, Stephan J.
AU - Madeo, Frank
AU - Carmona-Gutierrez, Didac
AU - Kroemer, Guido
N1 - Publisher Copyright:
© 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2019/9/2
Y1 - 2019/9/2
N2 - The age-induced deterioration of the organism results in detrimental and ultimately lethal pathologies. The process of aging itself involves a plethora of different mechanisms that should be subverted concurrently to delay and/or prevent age-related maladies. We have identified a natural compound, 4,4ʹ-dimethoxychalcone (DMC), which promotes longevity in yeast, worms and flies, and protects mice from heart injury and liver toxicity. Interestingly, both the DMC-mediated lifespan extension and the cardioprotection depend on macroautophagy/autophagy whereas hepatoprotection does not. DMC induces autophagy by inhibiting specific GATA transcription factors (TFs), independently of the TORC1 kinase pathway. The autophagy-independent beneficial effects of DMC might involve its antioxidative properties. DMC treatment results in a phylogenetically conserved, systemic impact on the metabolome, which is most prominently characterized by changes in cellular amino acid composition. Altogether, DMC exerts multiple, geroprotective effects by igniting distinct pathways, and thus represents a potential pharmacological agent that delays aging through multipronged effects.
AB - The age-induced deterioration of the organism results in detrimental and ultimately lethal pathologies. The process of aging itself involves a plethora of different mechanisms that should be subverted concurrently to delay and/or prevent age-related maladies. We have identified a natural compound, 4,4ʹ-dimethoxychalcone (DMC), which promotes longevity in yeast, worms and flies, and protects mice from heart injury and liver toxicity. Interestingly, both the DMC-mediated lifespan extension and the cardioprotection depend on macroautophagy/autophagy whereas hepatoprotection does not. DMC induces autophagy by inhibiting specific GATA transcription factors (TFs), independently of the TORC1 kinase pathway. The autophagy-independent beneficial effects of DMC might involve its antioxidative properties. DMC treatment results in a phylogenetically conserved, systemic impact on the metabolome, which is most prominently characterized by changes in cellular amino acid composition. Altogether, DMC exerts multiple, geroprotective effects by igniting distinct pathways, and thus represents a potential pharmacological agent that delays aging through multipronged effects.
KW - Cardioprotection
KW - GATA
KW - flavonoid
KW - liver protection
KW - longevity
UR - http://www.scopus.com/inward/record.url?scp=85068135064&partnerID=8YFLogxK
U2 - 10.1080/15548627.2019.1632623
DO - 10.1080/15548627.2019.1632623
M3 - Comment/debate
C2 - 31248332
AN - SCOPUS:85068135064
SN - 1554-8627
VL - 15
SP - 1662
EP - 1664
JO - Autophagy
JF - Autophagy
IS - 9
ER -