Aging and physiological barriers: mechanisms of barrier integrity changes and implications for age-related diseases

Mechanisms of aging affect physiological barriers at all levels of the biological system. Changes in tissue barrier permeability facilitate the infiltration of immune cells, toxins, infectious agents, and cytokines into the barrier areas, which causes autoimmune and inflammatory reactions, as well as the exit of unwanted cells beyond their niches. Preserving the integrity of cellular and intracellular membranes, as well as endothelial and epithelial barriers, is critical in preventing premature aging and age-related diseases. Molecular mechanisms of barrier maintenance are novel targets for anti-age interventions. The phenomenon of compartmentalization is one of the key traits of life. Biological membranes and histohematic barriers protect the internal environment of the cell and organism from endogenous and exogenous impacts. It is known that the integrity of these barriers decreases with age due to the loss of homeostasis, including age-related gene expression profile changes and the abnormal folding/assembly, crosslinking, and cleavage of barrier-forming macromolecules in addition to morphological changes in cells and tissues. The critical molecular and cellular mechanisms involved in physiological barrier integrity maintenance and aging-associated changes in their functioning are reviewed on different levels: molecular, organelle, cellular, tissue (histohematic, epithelial, and endothelial barriers), and organ one (skin). Biogerontology, which studies physiological barriers in the aspect of age, is still in its infancy; data are being accumulated, but there is no talk of the synthesis of complex theories yet. This paper mainly presents the mechanisms that will become targets of anti-aging therapy only in the future, possibly: pharmacological, cellular, and gene therapies, including potential geroprotectors, hormetins, senomorphic drugs, and senolytics.