The role of AGEs in muscle ageing and sarcopenia

Abstract

Sarcopenia is an ageing-related disease featured by the loss of skeletal muscle quality and function. Advanced glycation end-products (AGEs) are a complex set of modified proteins or lipids by non-enzymatic glycosylation and oxidation. The formation of AGEs is irreversible, and they accumulate in tissues with increasing age. Currently, AGEs, as a biomarker of ageing, are viewed as a risk factor for sarcopenia. AGE accumulation could cause harmful effects in the human body such as elevated inflammation levels, enhanced oxidative stress, and targeted glycosylation of proteins inside and outside the cells. Several studies have illustrated the pathogenic role of AGEs in sarcopenia, which includes promoting skeletal muscle atrophy, impairing muscle regeneration, disrupting the normal structure of skeletal muscle extracellular matrix, and contributing to neuromuscular junction lesion and vascular disorders. This article reviews studies focused on the pathogenic role of AGEs in sarcopenia and the potential mechanisms of the detrimental effects, aiming to provide new insights into the pathogenesis of sarcopenia and develop novel methods for the prevention and therapy of sarcopenia.

Fig. 1

Formation of advanced glycation end-products (AGEs).

Fig. 2

Molecular mechanisms of advanced glycation end-products (AGEs) leading to skeletal muscle atrophy. Arrows (→) indicate activation and stub lines (T) indicate inhibition. ActRⅡB, type 2 activin receptor; Akt, serine/threonine kinase; ALK4/5, activin receptor-like kinase 4/5; AMPK, adenosine 5‘-monophosphate; CAⅢ, carbonic anhydrase III; CK, creatine kinase; FOXO3, fork head box O3; IGF-1, insulin-like growth factor-1; IGFR, receptor for IGF-1; IR, receptor for insulin; mTOR, mammalian target of rapamycin; Murf1, muscle RING finger-1; NADPH, nicotinamide adenine dinucleotide phosphate; NF-kB, nuclear factor-κB; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator-1α; PI3K, phosphoinositide 3-kinase; PKC, protein kinase C; RAGE, receptor for AGEs; ROS, reactive oxygen species; Smad2/3, mothers against decapentaplegic 2/3; SIRT1, sirtuin1; UPS, ubiquitin-proteasome system; VDAC1, voltage-dependent anion selective channel 1. Created with BioRender.com, with permission.

Fig. 3

The pathogenic role of advanced glycation end-products (AGEs) in skeletal muscle. ECM, extracellular matrix; NMJ, neuromuscular junction. Created with BioRender.com, with permission.