Results: A 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.
Conclusion: Aging 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.
Keywords: Inflamm-aging, Gut microbiota, Lipopolysaccharide, p16, SAMHD1