A breakdown in communication? Understanding the effects of aging on the human small intestine

In the intestine a single layer of epithelial cells sealed together at their apical surfaces by tight junctions helps to prevent the lumenal commensal and pathogenic microorganisms and their toxins from entering host tissues. The intestinal epithelium also helps maintain homeostasis in the mucosal immune system by expressing anti-inflammatory cytokines in the steady-state and inflammatory cytokines in response to pathogens. Although the function of the mucosal immune system is impaired in elderly humans, the molecular mechanisms which cause this dramatic functional decline in immune function are poorly understood. Our current understanding of the effects of aging on the physical and immunological properties of the intestinal epithelial barrier is also very limited. In the present issue of Clinical Science , Man and colleagues provide further insight into the effects of aging on small intestinal barrier function in humans, and the influence that gut lumenal microorganisms may have on it. Using human terminal ileal biopsy tissues they show that intestinal permeability to solutes, but not macromolecules, was significantly increased in the intestines of elderly humans. This was accompanied by elevated expression of the pro-inflammatory cytokine IL-6 which appeared to modulate claudin-2 expression and solute permeability in the epithelium. Conversely, IL-8 synthesis in response to flagellin stimulation was reduced in the elderly intestines, but was not associated with effects on TLR5 expression. These data provide an important advance in our understanding on the effects of aging on intestinal permeability and the innate mucosal immune responsiveness in elderly humans.