Higher baseline TNF receptor and TNF-α expression in macrophages of aged mice

Recent studies by our lab have shown that aged mice are much more susceptible to toxicity affecting multiple organs caused by cancer immune stimulatory therapies. We have recently found that this toxicity is dependent upon TNF-α secreted by macrophages. This toxicity after immunotherapy is exacerbated in animals with higher fat content. We hypothesized that this may be due to up-regulation in baseline levels of TNF receptors. To test our hypothesis, we compared bone marrow derived macrophages from young (4 months), middle aged (10 months), and aged (20 months) mice and examined baseline expression of TNFR1α, TNFR1β, and TNFα by qPCR. At baseline, there were no differences between young and middle aged (4 and 10 months respectively) mice. However, aged (20 months) mice had significantly increased expression of TNFR1α (p<0.01), TNFR1β (p<0.01), and TNFα (p<0.05) compared with both young and middle aged mice. These results suggest that higher receptor expression may explain the heightened TNFα associated toxicity seen in aged mice. Further analysis of different tissues including adipose tissue as well as other parenchymal tissues may shed insights on this heightened pro-inflammatory response during aging.