Gut microbiota lipopolysaccharide accelerates inflamm-aging in mice.

Abstract

BackgroundThe constitutive inflammation that characterizes advanced age is termed inflamm-aging. This process is associated with age-related changes to immune homeostasis and gut microbiota. We investigated the relationship between aging and gut microbiota lipopolysaccharide (LPS)-inducible inflammation.ResultsA taxonomy-based analysis showed that aging resulted in increased prevalence of the phyla Firmicutes and Actinobacteria and a reduced prevalence of Bacteroidetes and Tenericutes, resulting in an increase in the Firmicutes to Bacteroidetes ratio. The levels of plasmatic and fecal lipopolysaccharides were higher in aged mice. Aging induced the expression of p16 and the activation of nuclear factor-kappa B (NF-κB) in the colon of aged mice. Interestingly, the expression level of sterile α-motif domain- and HD domain-containing protein 1 (SAMHD1) in the colon was higher in aged mice than in young mice, while cyclin-dependent kinase-2 and cyclin E levels were lower in aged mice than in young mice. The lipopolysaccharide fraction of fecal lysates (LFL) from young or aged mice increased p16 and SAMHD1 expression and NF-κB activation in peritoneal macrophages from wild-type mice, in a TLR4-dependent manner. However, LFLs did not induce NF-κB activation and SAMHD1 expression in peritoneal macrophages from TLR4-deificent mice, whereas they significantly induced p16 expression. Nevertheless, p16 expression was induced more potently in macrophages from WT mice than in macrophages from TLR4-deficient mice.ConclusionAging increased p16 and SAMHD1 expression, gut microbiota LPS production, and NF-κB activation; thereby, signifying that gut microbiota LPS may accelerate inflamm-aging and SAMHD1 may be an inflamm-aging marker.