Research press release


Nature Communications

Ageing: Natural compound with conserved anti-ageing properties



今回、Frank Madeoたちの研究グループは、細胞の健康を増進させる植物由来分子の一群であるフラボノイド類のスクリーニングを行い、酵母細胞において抗加齢作用を示すものを同定した。その結果、アシタバ(Angelica keiskei koidzumi)の葉に自然に含まれるフラボノイドの一種、4,4’-ジメトキシカルコン(DMC)が、酵母、線虫、キイロショウジョウバエに対して寿命延長効果を持ち、ヒト培養細胞の加齢関連の機能低下を軽減することも判明した。また、長時間の心筋虚血(心臓への血流の低下)を誘発したマウスにDMCを投与すると、心臓細胞が保護され、組織死の領域が縮小した。DMCの細胞保護作用にはオートファジーの活性化が必要で、こうした作用は、種を超えて保存されている全身性代謝を変化させることが明らかになった。


A natural compound has been identified that protects cells and delays ageing in species including yeast, worms and human cells in culture, reports a Nature Communications article published this week.

Ageing causes specific changes in the cell, and most manipulations known to extend lifespan stimulate a process in cells called autophagy. Autophagy is a recycling program that removes and degrades damaged cellular components including proteins and organelles, generating raw material to build new molecules. Compromised autophagy can result in age-related pathologies, including neurodegenerative disorders, when toxic or damaged molecules accumulate in the cell.

Frank Madeo and colleagues screened flavonoids, a group of plant-derived molecules known to promote cellular health, for anti-ageing effects in yeast cells. They identified 4,4’-dimethoxychalcone (DMC), a flavonoid naturally found in Angelica keiskei koidzumi leaves, as a lifespan-extending treatment in yeast, worms, and flies that also reduces age-associated cellular decline in human cells in culture. Treatment with DMC protected heart cells in mice after prolonged myocardial ischemia (reduced blood flow to the heart) leading to a smaller area of tissue death. The protective effects of DMC were found to require activation of autophagy and lead to systemic changes in metabolism that are conserved across species.

These observations confirm a conserved role for autophagy in cellular protection and longevity extension and represent a step in the identification and development of pharmacological anti-ageing therapies. However, additional research is required to determine if this is a promising strategy to prevent age-related decline in humans.

doi: 10.1038/s41467-019-08555-w

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