Aging-associated endotoxemia in men and mice is related to changes of intestinal barrier function and arginine metabolism in small intestine
Aging is also considered a state of low-grade inflammation, occurring in the absence of any overt infection often referred to as `inflammaging´. Therefore, maintaining intestinal homeostasis may be a target able to extend a healthier status in elderly people. Here, we report that even in healthy elderly men low grad bacterial endotoxemia is prevalent. Employing multiple mouse models, we show that while intestinal microbiota composition changes significantly during aging, old mice after fecal microbiota transplantation are not protected from aging-associated intestinal barrier dysfunction in the small intestine. Rather, intestinal arginine metabolism mediated through arginase and NO synthesis was altered in the small intestine of aging mice. Treatment with the arginase inhibitor norNOHA prevented aging-associated intestinal barrier dysfunction, low grad endotoxemia and delayed the onset of senescence in peripheral tissue e.g., liver and blood. Thus, intestinal arginine and NO metabolisms could be a target in the prevention of aging-associated decline and inflammaging.