The Intestinal Barrier Dysfunction as Driving Factor of Inflammaging

Abstract

The intestinal barrier, composed of the luminal microbiota, the mucus layer, and the physical barrier consisting of epithelial cells and immune cells, the latter residing underneath and within the epithelial cells, plays a special role in health and disease. While there is growing knowledge on the changes to the different layers associated with disease development, the barrier function also plays an important role during aging. Besides changes in the composition and function of cellular junctions, the entire gastrointestinal physiology contributes to essential age-related changes. This is also reflected by substantial differences in the microbial composition throughout the life span. Even though it remains difficult to define physiological age-related changes and to distinguish them from early signs of pathologies, studies in centenarians provide insights into the intestinal barrier features associated with longevity. The knowledge reviewed in this narrative review article might contribute to the definition of strategies to prevent the development of diseases in the elderly. Thus, targeted interventions to improve overall barrier function will be important disease prevention strategies for healthy aging in the future.

Keywords: aging; inflammaging; mucosal barrier.

Figure 1

Concept of inflammaging. Due to immunosenescence associated with changes in the innate and adaptive immune response, inflammatory pathways are increasingly activated, leading to a constant low-grade inflammatory state also termed inflammaging (modified after [10]). Abbreviations used: Up-arrow–increased; down-arrow—reduced; MHCII—major histocompatibility complex II; IFN-I—type-I interferon; DC—dendritic cell; NK—natural killer cell; BCR—B-cell receptor; Th1—type 1 T helper cell; PAMPs—pathogen-associated molecular patterns; DAMPs—damage-associated molecular patterns.

Figure 2

Schematic drawing of the intestinal barrier. The intestinal barrier includes a microbial, biochemical, physical, and immunological barrier. While the biochemical barrier consists of mucins and antimicrobial peptides, the physical barrier is composed of the epithelial monolayer with, e.g., enterocytes, goblet cells, enteroendocrine cells, Paneth cells, and microfold cells (M cells). Within the lamina propria, different immunological cells interact with the intestinal barrier, e.g., macrophages, dendritic cells, T cells, or mast cells. IgA: Immunoglobulin A. Modified after [3,11,12] and created with BioRender.com (accessed on 16 February 2022).

Figure 3

Stability of microbiota composition over the lifetime. During one’s lifetime, not only does the microbial composition change, but so too does its stability and diversity, which contributes to a more resilient microbial composition in adults (modified after [126]).