Attenuated Age-Impact on Systemic Inflammatory Markers in the Presence of a Metabolic Burden

BACKGROUND: The overall burden of chronic disease, inflammation and cardiovascular risk increases with age. Whether the relationship between age and inflammation is impacted by presence of an adverse metabolic burden is not known. METHODS: We determined inflammatory markers in humans (336 Caucasians and 224 African Americans) and in mice, representing a spectrum of age, weight and metabolic burden. RESULTS: In humans, levels of inflammatory markers increased significantly with age in subjects without the metabolic syndrome, (P=0.009 and P=0.037 for C-reactive protein, P<0.001 and P=0.001 for fibrinogen, P<0.001 and P=0.005 for serum amyloid-A, for Caucasians and African Americans, respectively). In contrast, trend patterns of inflammatory markers did not change significantly with age in subjects with metabolic syndrome in either ethnic group, except for fibrinogen in Caucasians. A composite z-score for systemic inflammation increased significantly with age in subjects without metabolic syndrome (P=0.004 and P<0.006 for Caucasians and African Americans, respectively) but not in subjects with metabolic syndrome (P=0.009 for difference in age trend between metabolic syndrome and non-metabolic syndrome). In contrast, no similar age trend was found in vascular inflammation. The findings in humans were paralleled by results in mice as serum amyloid-A levels increased across age (range 2-15 months, P<0.01) and were higher in ob/ob mice compared to control mice (P<0.001). CONCLUSIONS: Presence of a metabolic challenge in mice and humans influences levels of inflammatory markers over a wide age range. Our results underscore that already at a young age, presence of a metabolic burden enhances inflammation to a level that appears to be similar to that of decades older people without metabolic syndrome.