With the goal of mimicking age-associated low-grade inflammation in humans, we postulated that age-dependent impairment of gut integrity may permit low-level transfer of commensal bacteria or bacterial products to escape the lumen into the body, which would trigger variety of cell types to produce inflammatory agents that constitute low-grade systemic inflammation. Currently, two different models have been described that generate chronic inflammation in young mice. In one model high dose of 3-5% (w/v) dextran sodium sulfate (DSS) is provided in drinking water for 5 to 7 days followed by recovery for 7-10 days. This regimen is repeated at least three times to generate chronic inflammation, mirroring situations in which antigen-activated immune cells fail to turn down inflammatory response after an acute infection. In a second model lipopolysaccharide (LPS) is injected intravenously daily to simulate chronic infections such as noted in oral diseases. In our model we would like to mimic inflammation that represents age-associated deterioration of the gut barrier followed by transmission of commensal fecal bacteria and or bacterial products to the blood and tissues to elicit inflammatory responses. We expect that this mouse model will be useful in studying the cellular and molecular basis for the cause and effect of systemic inflammation in the aging of various tissues, age-associated chronic diseases such as Parkinson's Disease and obesity.
