Intestinal endotoxin: immunity – inflammation – aging as links in one chain

Abstract

Self-renewal of a population is a basic element of species development. This process is based on aging. Aging is a link between such equipollent fundamental notions as life and death. The basis of aging is low-intensity (with periods of exacerbations) inflammation, which is asymptomatic for a long time, i.e., does not show any clinical manifestations. The brightest example of this is atherosclerosis, which steadily progresses with age and becomes the most common cause of death. The inevitability of aging is genetically determined by the nature of the immune system and factors that regulate its activity. A special place among these factors belongs to intestinal endotoxin and stress, which determines the amount of LPS entering the systemic circulation. The main role of adaptive immunity is “cell surveillance” mediated by an astronomical number of receptors that put a “black mark” on both self and foreign antigens. The payment for maintaining purity of the cell pool is the autoimmune process, which apparently underlies low-intensity inflammation. The intensity of this self-destructive process (aging rate) is determined by the activity of innate immunity. The innate immunity depends on concentration of innate immunity ligands in the systemic circulation and the ability of the immune system to respond to them. Significant differences in the TLR4 and LPS interaction mechanism from other TLRs interactions with their ligands allows to qualify the intestinal endotoxin as an “exohormone” of adaptation, aging, and evolution. Thus, aging as a fundamental process is genetically predetermined by the very nature of the immune system and occurs with participation of intestinal endotoxin and stress, which are also mandatory factors of homeostasis. Aging may be slowed using known and so far unknown means for reversing systemic endotoxinaemia, a mandatory factor of homeostasis and general pathology.