Pharmacological depletion of macrophages leads to a reduction in inflammation and senescence in aged murine kidneys.

Aging is associated with chronic low-grade inflammation and cellular senescence, and macrophages are thought to contribute to these changes in the kidney. This study examined whether pharmacological inhibition of colony-stimulating factor 1 receptor (CSF1R) with PLX5622 modulates age-associated inflammatory and senescence-related changes in murine kidneys. Young and aged wild-type mice were treated with low-dose or high-dose PLX5622, and kidneys were analyzed for macrophage abundance, inflammatory markers, senescence-associated markers, and kidney injury markers. Aged kidneys showed increased expression of p16, IL-6, CX3CR1, and LCN2, together with higher numbers of F4/80-positive macrophages. Additional immunohistochemical analyses demonstrated increased CSF1R and p16 expression in F4/80-positive cells and increased senescence-associated β-galactosidase activity in aged kidneys. High-dose PLX5622 significantly reduced macrophage numbers in young and aged kidneys and lowered CX3CR1 expression, but was associated with increased blood urea nitrogen levels. In contrast, low-dose PLX5622 partially reduced macrophage abundance and significantly decreased IL-6, TNF-α, CX3CR1, p16, and senescence-associated β-galactosidase activity in aged kidneys without increasing blood urea nitrogen, while TIM1 remained unchanged. These findings indicate that CSF1R-sensitive macrophage populations contribute to age-associated inflammatory and senescence-related changes in the kidney and suggest that partial macrophage depletion may attenuate these processes without overt evidence of renal toxicity.