Renal Inflammaging: Mechanisms, Pathophysiology And Therapeutic Prospects
As we age, our kidneys can experience a continuous, low-grade inflammation, a process known as “inflammaging.” This isn’t just a passive consequence of getting older; the kidneys actively participate in this process, which significantly contributes to the development and progression of chronic kidney disease.
Several factors fuel this renal inflammaging. These include “immunosenescence,” which refers to the gradual decline and dysfunction of the immune system with age, “metabolic reprogramming,” where cells alter how they process energy, and “cellular senescence,” a state where cells stop dividing but remain active, accumulating in tissues. A crucial aspect is that certain kidney cells can adopt a “senescence-associated secretory phenotype” (SASP). This means these senescent cells begin to release a cocktail of inflammatory molecules, growth factors, and enzymes that further perpetuate inflammation, lead to scarring (fibrosis), and ultimately impair kidney function.
The underlying mechanisms driving this kidney damage are complex. They involve the activation of the “NLRP3 inflammasome,” a protein complex that triggers inflammatory responses, “mitochondrial dysfunction,” where the cell’s energy-producing powerhouses don’t work correctly, “epigenetic alterations,” which are changes in gene activity without altering the DNA sequence itself, and “gut-kidney crosstalk,” referring to the intricate communication between the gut microbiome and kidney health.
Fortunately, researchers are exploring promising avenues for diagnosis and treatment. Emerging diagnostic tools include “senescence and epigenetic clocks,” which can measure biological aging, and “single-cell signatures,” providing detailed insights into individual cell changes. Therapeutic strategies are also being developed, such as “senolytics,” drugs designed to selectively eliminate senescent cells, “SASP neutralization,” which aims to block the harmful substances released by these cells, and “immunometabolic modulators,” like SGLT2 inhibitors, which are medications that influence both the immune system and metabolic processes to protect the kidneys.
Source: link to paper