The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans
The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans
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DOI：
10.1038/s42255-019-0073-4
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发表时间：
2019-06-01
影响因子：
20.8
通讯作者：
Rinsch, Chris
中科院分区：
文献类型：
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作者：
Andreux, Penelope A.;Blanco-Bose, William;Rinsch, Chris
尿素A （UA）是一种天然的饮食微生物衍生代谢物，在老年动物和临床前衰老模型中被证明可以刺激线粒体自噬并改善肌肉健康(1)。在此，我们报告了一项首次人体临床试验的结果，在该试验中，我们对健康、久坐的老年人进行了为期4周的单剂量或多剂量的UA治疗。我们发现UA具有良好的安全性（主要结局）。在所有测试剂量下，UA在血浆中都是生物可利用的，用500 mg和1000 mg剂量的UA治疗4周后，老年人血浆中酰基肉碱和骨骼肌线粒体基因表达发生了变化（次要结局）。这些观察到的对线粒体生物标志物的影响表明，在人类定期口服UA后，UA诱导了线粒体和细胞健康改善的分子特征。
Urolithin A (UA) is a natural dietary, microflora-derived metabolite shown to stimulate mitophagy and improve muscle health in old animals and in preclinical models of aging(1). Here, we report the results of a first-in-human clinical trial in which we administered UA, either as a single dose or as multiple doses over a 4-week period, to healthy, sedentary elderly individuals. We show that UA has a favourable safety profile (primary outcome). UA was bioavailable in plasma at all doses tested, and 4 weeks of treatment with UA at doses of 500 mg and 1,000 mg modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression in elderly individuals (secondary outcomes). These observed effects on mitochondrial biomarkers show that UA induces a molecular signature of improved mitochondrial and cellular health following regular oral consumption in humans.