IRAP deficiency and IRAP inhibition in aged mice: kidney function, fibrosis and senescence
In aged mice, IRAP knockout or four weeks of IRAP inhibition was linked to preserved glomerular filtration rate and less renal fibrosis and senescence; this is mouse and cell-model evidence, not a proven human benefit. [1]
Automatic summary · not editorially reviewed
The key findings
In wild-type mice, glomerular filtration rate declined by 25% between 3 and 23 months of age, alongside rising albumin excretion, glomerulosclerosis, tubulointerstitial fibrosis and proximal-tubule senescent cells. [1]
IRAP knockout mice were protected against age-related GFR decline, renal fibrosis and senescence burden compared with age-matched wild-type mice. [1]
Four weeks of the IRAP inhibitor HFI-419 in 28-month-old wild-type mice prevented age-related GFR decline and attenuated cellular senescence markers; in cultured proximal tubule cells, IRAP inhibition reduced oxidative-stress-driven senescence. [1]
The source at a glance
- Study type / format
- Animal and cell-model study (abstract)
- Population / context
- Wild-type and IRAP knockout mice aged up to 28 months, plus cultured proximal tubule and collecting duct cells.
- Summary based on
- Study abstract
- Original publication
- October 1, 2026
Kidney ageing in wild-type mice over 3 to 23 months
The researchers asked whether the angiotensin IV/insulin-regulated aminopeptidase (IRAP) axis of the renin-angiotensin system contributes to kidney ageing. In wild-type mice, glomerular filtration rate (GFR) fell by 25% between 3 and 23 months of age. At the same time, albumin excretion, glomerulosclerosis, tubulointerstitial fibrosis and accumulation of senescent cells in proximal tubules rose markedly. These observations describe what happened with age in this mouse strain; they do not show that IRAP causes these changes.
Supporting source [1]
IRAP knockout and four-week inhibition in old mice
IRAP knockout mice were protected against the age-related decline in GFR, renal fibrosis and senescence burden compared with age-matched wild-type mice. Separately, wild-type mice aged 28 months received the IRAP inhibitor HFI-419 for four weeks (500 ng/kg/min). This also prevented the age-related GFR decline and attenuated expression of cellular senescence markers. The comparison was between knockout and wild-type mice, and between inhibitor-treated and untreated old mice; the abstract does not report the size of these groups.
Supporting source [1]
Cell-model mechanism and limits of this abstract
In cultured proximal tubule cells, IRAP inhibition reduced the pro-senescent effects of oxidative stress. This was accompanied by shifts in the metabolic phenotype of these cells, suggesting the protective effects may act in part through mitochondrial function. The authors conclude that IRAP inhibition has therapeutic potential for pathological cardiorenal ageing. However, this abstract reports mouse and cell-culture experiments only; it does not show that IRAP inhibition preserves kidney function or extends lifespan in humans. The full text was not reviewed.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Findings come from mouse models and cultured cells, group sizes and statistical details are not reported here, and no human outcome is shown.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Walton SL, Ansari A, Mirabito Colafella KM, Hilliard Krause LM, Barsha G, Kett MM, Chai SY, Garovic VD, Denton KM. · europepmc.org · October 1, 2026