Pharmacological depletion of macrophages leads to a reduction in inflammation and senescence in aged murine kidneys
- 1Corresponding author.
- 2Department of Neurology, Jena University Hospital, Friedrich-Schiller University Jena, Am Klinikum 1, Jena, 07747, Germany
Abstract
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.
Related
- MKP‐2 Genetic Depletion Modulates Adipose Lipid Composition, Cellular Senescence, and Aging in Mice
- Depletion of border-associated macrophages impairs CSF flow and exacerbates extranuclear mutant Huntingtin aggregation in the zQ175DN mouse model of Huntington’s disease
- Cholesterol-Induced Senescent Macrophages and Evaluation of Cellular Senescence Phenotypes
- Low-molecular-weight Ulva lacinulata extract exhibiting anti-inflammatory and pro-autophagic activities in RAW 264.7 macrophages: a promising candidate for the development of active ingredients targeting low-grade inflammation
- Pharmacological targeting of the NLRP3 LRR domain with isothiazolinones overcomes CRID3-resistant inflammation
BibTeX
@article{stojiljkovic2026pharmacological,
title = {{Pharmacological depletion of macrophages leads to a reduction in inflammation and senescence in aged murine kidneys}},
author = {Milan R. Stojiljkovic and Christian Schmeer and Otto W. Witte},
journal = {Immunobiology},
year = {2026},
month = oct,
doi = {10.1016/j.imbio.2026.153259},
url = {https://doi.org/10.1016/j.imbio.2026.153259},
note = {CC BY},
}
RIS
TY - JOUR
TI - Pharmacological depletion of macrophages leads to a reduction in inflammation and senescence in aged murine kidneys
AU - Milan R. Stojiljkovic
AU - Christian Schmeer
AU - Otto W. Witte
PY - 2026
DA - 2026/10/30
JO - Immunobiology
DO - 10.1016/j.imbio.2026.153259
UR - https://doi.org/10.1016/j.imbio.2026.153259
AB - 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.
SN - 0171-2985
SN - 1878-3279
ER -