Abstract

Aging alters lymphatic vessel structure (by increasing the size of low muscle cell investiture zones), ultrastructure (through loss of the glycocalyx), and proteome composition causing a concomitant increase in lymphatic permeability. Our recent studies have shown that the contractile function of aged lymphatic vessels is depleted with abolished role of nitric oxide and an increased role of lymphatic-born histamine in flow-dependent regulation of lymphatic phasic contractions and tone. Thus, aging-related reduced vessel functionality and increased oxidative stress of the lymphatic vasculature facilitate the spread of pathogens into perilymphatic tissues. In addition, aging causes the basal activation of the perilymphatic mast cells, which, in turn, restricts the recruitment/activation of MHCII+ -positive cells and eosinophils in perilymphatic tissues. This aging-associated basal activation of perilymphatic mast cells limits proper functioning of the mast cell/histamine/NF-kB axis that is essential for the regulation of lymphatic vessel transport and barrier functions as well as for both the interaction and trafficking of immune cells near and within lymphatic collecting vessels. Cumulatively these alterations play crucial roles in the progression of aging-related pathogenesis in inflammation and immunity.

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