Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging.

Macroautophagy decreases with age, and this change is considered a hallmark of the aging process. It remains unknown whether mitophagy, the essential selective autophagic degradation of mitochondria, also decreases with age. In our analysis of mitophagy in multiple organs in the mito-QC reporter mouse, mitophagy is either increased or unchanged in old versus young mice. Transcriptomic analysis shows marked upregulation of the type I interferon response in the retina of old mice, which correlates with increased levels of cytosolic mtDNA and activation of the cGAS/STING pathway. Crucially, these same alterations are replicated in primary human fibroblasts from elderly donors. In old mice, pharmacological induction of mitophagy with urolithin A attenuates cGAS/STING activation and ameliorates deterioration of neurological function. These findings point to mitophagy induction as a strategy to decrease age-associated inflammation and increase healthspan.

Gut Bacteria Involved in Ellagic Acid Metabolism To Yield Human Urolithin Metabotypes Revealed.

We aimed to elucidate the gut bacteria that characterize the human urolithin metabotypes A and B (UM-A and UM-B). We report here a new bacterium isolated from the feces of a healthy woman, capable of producing the final metabolites urolithins A and B and different intermediates. Besides, we describe two gut bacterial co-cultures that reproduced the urolithin formation pathways upon in vitro fermentation of both UM-A and UM-B. This is the first time that the capacity of pure strains to metabolize ellagic acid cooperatively to yield urolithin profiles associated with UM-A and UM-B has been demonstrated. The urolithin-producing bacteria described herein could have potential as novel probiotics and in the industrial manufacture of bioactive urolithins to develop new ingredients, beverages, nutraceuticals, pharmaceuticals, and (or) functional foods. This is especially relevant in UM-0 individuals since they cannot produce bioactive urolithins.