Impact of a young parabiotic circulation on renal injury and fibrosis in aged mice

Abstract Background Ageing increases susceptibility to acute kidney injury and fibrotic chronic kidney disease, with mechanisms remaining incompletely understood. Results of parabiotic studies show that a young circulation can reverse ageing phenotypes in the brain and heart. We tested the hypothesis that young circulating factors would protect aged mice from experimental acute kidney injury and chronic kidney disease. Methods Parabiotic pairs were established between young (8 weeks old) and old (14 months old) C57BL6/CD45.1 mice to generate young–young, old–old, old–young, and young–old pairings for 28 days. Acute kidney injury was induced via bilateral renal ischaemia reperfusion injury, and fibrosis via unilateral ureteric obstruction for 5–14 days. Creatinine was measured at baseline and after injury. Transcriptome data were assessed at baseline. Fibrosis and macrophage infiltration were measured to assess renal injury in young and old animals in matched and mismatched parabiotic pairs. Data are given as mean [SD]. Findings Despite normal serum creatinine concentrations, old animals in both old–old and old–young pairings had higher levels of baseline fibrosis than did young–old and young–young pairs (% collagen in young 2·6 [0·3] vs old 8·4 [0·7], p vs 61·6 [21·6], p=0·032). In the unilateral ureteric obstruction model, old animals in old–young pairs had reduced scarring, macrophage infiltration, and inflammatory gene transcription compared with old–old pairs (all p Interpretation Our data show that the aged kidney has a distinct transcriptomic appearance and worsened injury outcomes. A shared young circulation modifies acute kidney injury and chronic kidney disease, indicating the presence of a factor that modifies renal ageing. Funding Wellcome Trust.