The lymphatic system is a parallel circulatory system responsible for moving fluid, immune cells, and a range of vital molecules around the body. It is of particular importance to immune function, allowing components of the immune system to carry messages from place to place in the body, and communicate and coordinate the immune response at the hubs known as lymph nodes. Like all tissues in the body, the lymphatic system is negatively impacted by aging, and this has widespread detrimental effects throughout the body and brain.

For example, lymph nodes become disrupted in structure and function by the presence of senescent cells and consequent fibrosis as tissue maintenance runs awry in the face of the senescence-associated secretory phenotype. The consequences of this are well demonstrated in a recent paper: very old mice and primates suffering from immunosenescence, an immune system with a poor response to pathogens, cannot benefit from the addition of new, functional immune cells. Their lymph nodes are too structurally impacted to allow the new cells to coordinate an effective immune response. Given that fibrosis in a number of tissues has been reversed in animal models via use of senolytics to clear senescent cells and their inflammatory signaling, it is possible that lymph node aging might be reversed to some degree. If the structure cannot be regenerated, however, then there are efforts underway to produce artificial lymph nodes that can be transplanted to integrate with the lymphatic system.

It isn't just a matter of lymph nodes, of course. Lymphatic vessels actively pump their contents, and this pumping function declines and becomes erratic with advancing age. Other forms of degeneration also take place, impairing the ability of immune cells and their signals to move about the body. This is a harder problem to solve, given its distributed nature, and that it probably arises due to contributions from most of the underlying forms of molecular damage that cause aging. It is important for the research community to keep working on means of repair for all forms of damage, not just focus on the approaches, like senolytics, that are closest to practical clinical use.

Reduced lymphatic function contributes to age-related disease