Knockout of receptor for advanced glycation end‐products attenuates age‐related renal lesions. Issue 2 (22nd February 2019)

• Record Type: Journal Article
• Authors: Teissier, Thibault; Quersin, Valentine; Gnemmi, Viviane; Daroux, Maité; Howsam, Mike; Delguste, Florian; Lemoine, Cécile; Fradin, Chantal; Schmidt, Ann‐Marie; Cauffiez, Christelle; Brousseau, Thierry; Glowacki, François; Tessier, Frédéric J.; Boulanger, Eric; Frimat, Marie
• Is Part Of: Aging cell. Volume 18:Issue 2(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-02-22
• Subjects: advanced glycation end‐products -- amyloidosis -- chronic kidney disease -- nephrosclerosis -- receptor for AGEs -- renal aging; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.12850
• Languages: English
• ISSNs: 1474-9718

Abstract

Abstract: Pro‐aging effects of endogenous advanced glycation end‐products (AGEs) have been reported, and there is increasing interest in the pro‐inflammatory and ‐fibrotic effects of their binding to RAGE (the main AGE receptor). The role of dietary AGEs in aging remains ill‐defined, but the predominantly renal accumulation of dietary carboxymethyllysine (CML) suggests the kidneys may be particularly affected. We studied the impact of RAGE invalidation and a CML‐enriched diet on renal aging. Two‐month‐old male, wild‐type (WT) and RAGE −/− C57Bl/6 mice were fed a control or a CML‐enriched diet (200 μg CML/gfood ) for 18 months. Compared to controls, we observed higher CML levels in the kidneys of both CML WT and CML RAGE −/− mice, with a predominantly tubular localization. The CML‐rich diet had no significant impact on the studied renal parameters, whereby only a trend to worsening glomerular sclerosis was detected. Irrespective of diet, RAGE −/− mice were significantly protected against nephrosclerosis lesions (hyalinosis, tubular atrophy, fibrosis and glomerular sclerosis) and renal senile apolipoprotein A‐II (ApoA‐II) amyloidosis ( p < 0.001). A positive linear correlation between sclerosis score and ApoA‐II amyloidosis score ( r = 0.92) was observed. Compared with old WT mice, old RAGE −/− mice exhibited lower expression of inflammation markers and activation of AKT, and greater expression of Sod2 and SIRT1. Overall, nephrosclerosis lesions and senile amyloidosis were significantly reduced in RAGE −/− mice, indicating a protective effect of RAGE deletion with respect to renal aging. This could be due to reduced inflammation and oxidative stress in RAGE −/− mice, suggesting RAGE is an important receptor in so‐called inflamm‐aging.