Reviewing What is Known of Structural Deterioration of Lymph Nodes with Aging
Researchers have shown that the aging of lymph nodes prevents restoration of immune cell populations from improving the immune response. The immune system uses lymph nodes as centers of coordination, but with age these structures deteriorate and become fibrotic. Here, researchers review what is known of this structural and functional lymph node aging. At this point it is unclear as to the best approaches to restore aged lymph nodes, as fibrosis in general remains an unsolved problem. Clearing senescent cells may help, but other strategies may be needed, such as the creation and transplantation of artificial lymph nodes.
Studies have indicated that as individuals age, there is a reduction in the size of the lymph node (LN), accompanied by degenerative changes such as the development of fibrosis and lipomatosis. There is also evidence of changes in the structure of the LN endothelium, leading to decrease in immune cell recruitment. As a result, the immune cell number present in the LN diminishes. Furthermore, during ageing, the number and size (area) of germinal centres (GC) is reduced by approximately 30%-50% . This deficit results in reduced humoral immunity, leading to impaired antibody production and an increased susceptibility to infections in individuals over the age of 65. Consequently, it can be speculated that the disorganisation of the LN structure play a significant role in the ageing of the immune system.
The architecture of the LN is created and supported by LN stroma cells (LNSCs), comprising heterogeneous populations of mesenchymal cells and endothelial cells. LNSCs organise the LN into distinct compartments to support immune cell retention, activation, proliferation, and differentiation in homeostatic conditions and in response to antigenic stimulation. To support and maintain the distinct yet diverse immune cell niches within the LN, LNSCs secrete various growth factors and chemokines to ensure immune cells are correctly localised to their unique niches and receive appropriate survival signals. Thus, LNSC plays an important role in ensuring immune cell homeostasis, activation of immune responses during infection, and accordingly, any age-associated changes to LNSCs may significantly hamper the overall function of the LN as a hub for immunosurveillance.
As a matter of fact, studies performed in the recent years have begun to shed light how age-associated changes to LNSCs impairs the generation of protective immunity against infection and after vaccination. The observation that the older adults are not able to generate effective long-term protective immunity after vaccination highlights the necessity to comprehend how underlying age-associated changes to LNSC precipitates into impaired immune responses, and further research may potentiate development of therapeutic strategies that could enhance immune responses by targeting the aged LNSCs.