Knockout of receptor for advanced glycation end-products attenuates age-related renal lesions

Aging Cell
Thibault TeissierMarie Frimat

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) wa...Continue Reading

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Citations

Sep 9, 2019·Aging·Marie FrimatEric Boulanger
May 20, 2019·Biogerontology·Lynne Cox, Katarzyna Goljanek-Whysall
Aug 8, 2020·Frontiers in Physiology·Munehiro KitadaDaisuke Koya
Sep 19, 2019·Biochimica Et Biophysica Acta. General Subjects·Babett BartlingAndreas Simm
Jan 24, 2021·Experimental Gerontology·Frédéric N DaussinSteve Lancel
Mar 7, 2021·International Journal of Molecular Sciences·Anne GrunenwaldMarie Frimat
Apr 1, 2021·Journal of Cellular and Molecular Medicine·Peipei ZhengJian Xiao
Nov 2, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Daniel PrantnerStefanie N Vogel
May 22, 2021·Free Radical Biology & Medicine·Xia-Qing WuYing-Yong Zhao

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Methods Mentioned

BETA
glycation
electron microscopy
protein assay

Software Mentioned

GraphPad Prism

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