Age and Caloric Restriction Diets Are Confounding Factors That Modify the Response to Lipopolysaccharide by Peritoneal Macrophages in C57bl/6 Mice

Aging is the result of several detrimental changes that lead to a decrease in homeostasis, an increase in the incidence of degenerative diseases, and death. A caloric-restricted diet (CR), which consists of a significant reduction in calorie intake (40%) without malnutrition, has been shown to delay the onset of age-related diseases and pathologies and to extend life span. The aims of this study were to assess the effects of aging and CR on lipopolysaccharide (LPS)-dependant cytokine production by peritoneal macrophages (PMphis). Resident naïve PMphis were isolated from 2- to 24-month-old male C57BL/6 mice and were stimulated with Escherichia coli LPS (100 ng/mL) for 1 to 5 h in culture conditions. A linear decrease in the production of LPS-induced tumor necrosis factor alpha (TNF-alpha) and interleukin (IL) 10 was observed with age. LPS-induced IL-6 and IL-1beta levels were also reduced with age, but in a nonlinear fashion. Expression of CD14, the major receptor for LPS, on the PMphi surface was also observed to decline with age. Moreover, TNF-alpha production by PMphis was reduced in mice undergoing the two different CR diets of limited daily feeding and intermittent fasting, as compared with ad libitum-fed mice. The results of this study add the new variables age and diet to the paradigm proposing that the response to LPS is modulated by multiple components, including genetic background and sex.