Kidney cells themselves become inflammatory factories during aging, secreting harmful compounds through a senescence-associated secretory phenotype (SASP) that accelerates both kidney disease and systemic aging. Key renal cell types—tubular epithelial cells, podocytes, and mesangial cells—undergo senescence and release inflammatory signals that perpetuate damage through NLRP3 inflammasome activation, mitochondrial dysfunction, and epigenetic changes. This positions kidneys as active drivers of "inflammaging" rather than passive victims.
This mechanistic insight reshapes our understanding of kidney-aging interactions and opens promising therapeutic avenues. The identification of specific cellular senescence pathways suggests senolytics—drugs that eliminate senescent cells—could simultaneously treat kidney disease and slow systemic aging. SGLT2 inhibitors, already used for diabetes, show potential as immunometabolic modulators targeting these pathways. The review's emphasis on gut-kidney crosstalk also highlights how microbiome interventions might influence renal inflammaging. While the evidence comes from observational studies requiring clinical validation, this framework represents a paradigm shift toward viewing kidney health as central to healthy aging, potentially transforming treatment strategies for the growing population of older adults with chronic kidney disease.
