Modulation of soluble receptor for advanced glycation end-products (RAGE) isoforms and their ligands in healthy aging | Zendy

Francesco Scavello | Zendy; Filippo Zeni | Zendy; Calogero C. Tedesco | Zendy; Emanuela Mensa’ | Zendy; Fabrizio Veglia | Zendy; Antonio Domenico Procopio | Zendy; Anna Rita Bonfigli | Zendy; Fabiola Olivieri | Zendy; Angela Raucci | Zendy

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Modulation of soluble receptor for advanced glycation end-products (RAGE) isoforms and their ligands in healthy aging

Author(s) -

Francesco Scavello,

Filippo Zeni,

Calogero C. Tedesco,

Emanuela Mensa’,

Fabrizio Veglia,

Antonio Domenico Procopio,

Anna Rita Bonfigli,

Fabiola Olivieri,

Angela Raucci

Publication year - 2019

Publication title -

aging

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.473

H-Index - 90

ISSN - 1945-4589

DOI - 10.18632/aging.101860

Subject(s) - glycation , rage (emotion) , medicine , endocrinology , receptor , advanced glycation end product , hmgb1 , population , insulin resistance , downregulation and upregulation , waist , diabetes mellitus , body mass index , chemistry , immunology , biology , biochemistry , gene , environmental health , neuroscience

The receptor for advanced glycation end-products (RAGE) recognizes several ligands involved in inflammatory diseases. Two circulating soluble isoforms exist: esRAGE derived from alternative splicing and cRAGE generated by the membrane-bound RAGE (FL-RAGE) proteolysis. Together, esRAGE and cRAGE constitute sRAGE and function as decoy receptors preventing FL-RAGE/ligands binding.We determined serum concentration of both, esRAGE and cRAGE, and their ligands AGEs, HMGB1 and S100A8/A9 in a healthy population of 169 subjects aged 20-90 years. cRAGE showed a negative (r=-0.375, P<0.0001) while AGEs (r=0.160, P=0.0384) and S100A8/A9 (r=0.207, P=0.0091) a positive correlation with age. esRAGE did not change during aging and inversely correlated with Hemoglobin, ALT, insulin, HOMA index, Waist-Hip ratio (W/H), Waist Circumference (WC) and positively with AGEs. cRAGE exhibited also an inverse correlation with WC, W/H, PAI-1, HMGB1, AGEs and S100A8/A9. Age, W/H, HMGB1, S100A8/A9 and AGEs are independent predictors of cRAGE, whereas W/H and AGEs associate with esRAGE. Treatment of cells with glycated albumin reduced cRAGE production and upregulated FL-RAGE.These results indicate that in a healthy population cRAGE is a biomarker of aging while esRAGE represents a more reliable marker of obesity and insulin resistance. Hence, sRAGE isoforms levels could be differentially associated with age-related diseases risk factors.

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