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Researchers here discuss the ways in which the aging of the immune system influences the aging of the kidney, such as through disruption of the normal participation of immune cells in tissue maintenance and repair. With age the immune system falls into a state of chronic inflammation, and unresolved inflammatory signaling is disruptive to the structure and operation of tissues throughout the body. The kidney is but one example of how this contributes to the declines of aging.
With the steady increase in the number of elderly individuals globally, age-related diseases emerge as a major challenge to health care workers. Apart from functional and structural changes in the kidneys introduced by aging, immune system decline also significantly increases the risk of age-related kidney diseases. Immunosenescence is a loose definition of age-related changes in the innate and adaptive immune responses, which is characterized by shrinkage of naïve immune cell reservoirs, accumulation of late-stage differentiated cells with a senescent phenotype, and immunoglobulin class switching. These changes in the immune system result in two seemingly incompatible aspects: diminished immune response and increased inflammatory response, also known as inflammaging.
Tubular epithelial cells (TECs) senescence and tertiary lymphoid tissue formation occur following acute kidney injury. Senescent kidney cells promote a chronic inflammatory microenvironment, which can subsequently cause local tissue damage, hinder tissue repair, and promote immune system senescence. Intrarenal inflammation underlies the development of renal fibrosis and chronic kidney disease (CKD) later in life. Immunosenescence is exaggerated in patients with CKD and end-stage renal disease (ESRD). Hallmarks of immunosenescence, including decreased naïve T cells, reduced CD28 expression, and increased proinflammatory macrophages, are convincing predictors of mortality in patients with CKD and ESRD. Renal replacement therapy for old patients with ESRD results in a lower acute rejection rate after the kidney transplantation. However, immunosenescence may increase the risk of chronic, but severe, graft failure. In addition, immunosenescence has been reported to speed up during kidney transplantation and immunosuppressive treatment.