Amazentis SA, EPFL Innovation Park, Bâtiment C, Lausanne, Switzerland.
Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Nat Metab. 2019 Jun;1(6):595-603. doi: 10.1038/s42255-019-0073-4. Epub 2019 Jun 14.
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. 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.
尿石素 A（UA）是一种天然的饮食来源，微生物衍生的代谢物，已被证明可刺激自噬并改善老年动物和衰老的临床前模型中的肌肉健康。在这里，我们报告了一项首次在人体临床试验中的结果，我们给健康的久坐老年人单次或连续 4 周服用 UA。我们表明 UA 具有良好的安全性（主要结果）。在所有测试剂量的血浆中均可检测到 UA 的生物利用度，并且在 500mg 和 1000mg 的剂量下用 UA 治疗 4 周可调节老年人的血浆酰基辅酶 A 和骨骼肌线粒体基因表达（次要结果）。这些对线粒体生物标志物的观察结果表明，UA 诱导了人类经常口服后改善线粒体和细胞健康的分子特征。
