A brief history of studying the role of intestinal factor in aging and/or induction of systemic inflammation: Achievements, challenges, and prospects

Abstract

Studying the role of intestinal factor in the rate of aging, induction of inflammation, and progression of diseases is inextricably (directly or indirectly) associated with the great Russian scientist I.I. Mechnikov. His intuition initiated studying the long-livers’ microbiota and the surgical removal of the colon (as a rudiment and source of toxic rotting products), which did not bring any scientific or practical success. These studies were over a little less than 100 years ago marking the end of the first stage of research. The second stage started in parallel with the first one and consisted in studying biological properties and structure of endotoxin (lipopolysaccharide, LPS). LPS molecules are as numerous on the earth as in the air since LPS is thermally stable and generated by blue-green algae that have inhabited the World Ocean two billion years ago. The third stage of studying the intestinal factor in general pathology started in Russia one third of a century ago at the junction of the two abovementioned, paralleling endeavors – postulating systemic endotoxemia as an obligate biological phenomenon and discovery of the LPS receptor (TLR4) of innate immunity. TLR4 is carried by humans, animals, fish, sponges, and even plants, which suggests that LPS is not only an adaptive exohormone but also an obligate factor of evolution. This implies population self-renewal, which requires that the obligate lifesupport
factors must also possess an opposite effect, including stress and intestinal LPS. The ability of LPS suppressors to enhance the therapeutic and prophylactic process makes promising a possibility of slowing aging. The primary tasks for achieving this goal are determining the range of systemic endotoxemia physiological indexes in all age groups and creating a readily accessible new generation of methods for selective elimination of LPS from blood (hemodialysis) and intestine (enterosorption) that could be developed on the basis of aptamers.