Influence of intestinal microbiota in immune senescence

2011 new Scholar Award in aging

The total surface of the intestinal epithelium reaches 300m2 in humans, roughly the size of a tennis court. The intestines of vertebrate organisms are exposed daily to large amounts of antigens that in the great majority are innocuous, originating from the diet and from the resident commensal microbiota. Additionally, the intestinal mucosa is a major entry site for pathogens, including bacteria, viruses, fungi and parasites. The intestine hosts a complex immune system that accounts for the majority of lymphocytes and antibodies in the body. This vast immune system must avoid penetration and spreading of pathogens while avoiding excessive or unnecessary immune responses that could jeopardize the integrity of the mucosal epithelial barrier and lead to chronic inflammatory diseases. Indeed, chronic inflammation is considered to be involved in the pathogenesis of all main age-related diseases, such as Alzheimer's disease, atherosclerosis, diabetes and cancer.

We hypothesize that the intestinal microbiota plays an important role in immune senescence. We will investigate whether chronic exposure to microbial antigens represents a major driver for the changes seen in the function of innate and adaptive immune cells, such as the development of the chronic inflammatory state observed in aged animals.

Daniel Mucida Ph.D.
Rockefeller University