Urolithin A

Urolithin A is a microflora-derived metabolite [1].

Urolithin A is a natural food metabolite that stimulates mitophagy and reduces the accumulation of dysfunctional mitochondria with age, thus maintaining mitochondrial biogenesis and respiratory capacity in cells [1]. Urolithin A is the most active and effective gut metabolite that acts as a potent anti-inflammatory and anti-oxidant agent [2].

In CD4⁺ T cells, treatment of murine CD4⁺ T cells with Urolithin A (10 μM, 3 days) significantly blunted store operated Ca²⁺ entry (SOCE), which was accompanied by significant downregulation of STIM1/2 and Orai1 transcript levels and protein abundance. In addition, urolithin A treatment (5, 10, 20, 50 μM) further increased miR-10a-5p abundance in CD4⁺ T cells, in a dose-dependent manner [2].

In healthy, sedentary elderly individuals, 4 weeks of oral treatment with urolithin A at doses of 500 mg and 1000 mg modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression, with favourable safety profiles [1].

References:

[1]. Pénélope A. Andreux, Blanco-Bose W, et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism, 2019, 1: 595-603.

[2]. Zhang S, Al-Maghout T, Cao H, et al. Gut Bacterial Metabolite Urolithin A (UA) Mitigates Ca2+ Entry in T Cells by Regulating miR-10a-5p. Frontiers in Immunology, 2019, 10(1737): 1-12.