The Dual Role of Cellular Senescence in Macrophages: Unveiling the Hidden Driver of Age-Related Inflammation in Kidney Disease.

Aging is a complex biological process that involves the gradual decline of cellular, tissue, and organ functions. In kidney, aging manifests as tubular atrophy, glomerulosclerosis, and progressive renal function decline. The critical role of senescence-associated macrophage in diseases, particularly kidney diseases, is increasingly recognized. During this process, macrophages exhibit a range of pro-damage response to senescent tissues and cells, while the aging of macrophages themselves also significantly influences disease progression, creating a bidirectional regulatory role between aging and macrophages. To explore this bidirectional mechanism, this review will elucidate the origin, characteristic, phenotype, and function of macrophages in response to the senescence-associated secretory phenotype (SASP), extracellular vesicles from senescent cells, and the senescence cell-engulfment suppression (SCES), particularly in the context of kidney disease. Additionally, it will discuss the characteristics of senescent macrophage, such as common markers, and changes in autophagy, metabolism, gene regulation, phagocytosis, antigen presentation, and exosome secretion, along with their physiological and pathological impacts on renal tissue cells. Furthermore, exploring therapies and drugs that modulate the function of senescent macrophages or eliminate senescent cells may help slow the progression of kidney aging and damage.