4.7 Article

Impairments of intestinal arginine and NO metabolisms trigger aging-associated intestinal barrier dysfunction and 'inflammaging'

Journal

REDOX BIOLOGY
Volume 58, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.redox.2022.102528

Keywords

Aging; Endotoxin; Nitric oxide; Intestinal permeability; Microbiota

Funding

  1. German Research Foundation [SPP1656, FKZ: BE2376/8-1, CA1708/1-1]
  2. European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [859890]
  3. Herzfelder Family Foundation/Austrian Science Fund FWF [P35271]
  4. Austrian Science Fund FWF [I04844]
  5. Marie Curie Actions (MSCA) [859890] Funding Source: Marie Curie Actions (MSCA)
  6. Austrian Science Fund (FWF) [P35271] Funding Source: Austrian Science Fund (FWF)

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Aging is associated with low grade inflammation, called "inflammaging". Maintaining intestinal homeostasis may help extend the healthy status of older adults. In this study, it was found that even in healthy older men, low grade bacterial endotoxemia is common. Additionally, while intestinal microbiota composition changes significantly during aging, fecal microbiota transplantation does not protect against aging-associated intestinal barrier dysfunction in mice.
Aging is considered a state of low grade inflammation, occurring in the absence of any overt infection often referred to as 'inflammaging'. Maintaining intestinal homeostasis may be a target to extend a healthier status in older adults. Here, we report that even in healthy older men low grade bacterial endotoxemia is prevalent. In addition, employing multiple mouse models, we also show that while intestinal microbiota composition changes significantly during aging, fecal microbiota transplantation to old mice does not protect against aging-associated intestinal barrier dysfunction in small intestine. Rather, intestinal NO homeostasis and arginine metabolism mediated through arginase and NO synthesis is altered in small intestine of aging mice. Treatment with the arginase inhibitor norNOHA prevented aging-associated intestinal barrier dysfunction, low grade endotoxemia and delayed the onset of senescence in peripheral tissue e.g., liver. Intestinal arginine and NO metabolisms could be a target in the prevention of aging-associated intestinal barrier dysfunction and subsequently decline and 'inflammaging'.

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