Maximus Peto’s Commentary
These researchers report on what appears to be an interesting set of observations about AGEs in the context of collagen in aged human tissue samples. They report increased spacing and decreased D-period length in both aged tissues and in their ribose model of in vitro glycation. They also found that AGEs “severely limit fiber-fiber and fibril-fibril sliding”, though this was apparently only observed in the in vitro glycated tendons (apparently not from human tissue samples), so skepticism on this last bit may be appropriate.
Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue.
Matrix Biol. 2017 May;59:95-108.
Gautieri A, Passini FS, Silván U, Guizar-Sicairos M, Carimati G, Volpi P, Moretti M, Schoenhuber H, Redaelli A, Berli M, Snedeker JG
PubMed publication date (edat): 10/23/2016
Concurrent with a progressive loss of regenerative capacity, connective tissue aging is characterized by a progressive accumulation of Advanced Glycation End-products (AGEs). Besides being part of the typical aging process, type II diabetics are particularly affected by AGE accumulation due to abnormally high levels of systemic glucose that increases the glycation rate of long-lived proteins such as collagen. Although AGEs are associated with a wide range of clinical disorders, the mechanisms by which AGEs contribute to connective tissue disease in aging and diabetes are still poorly understood. The present study harnesses advanced multiscale imaging techniques to characterize a widely employed in vitro model of ribose induced collagen aging and further benchmarks these data against experiments on native human tissues from donors of different age. These efforts yield unprecedented insight into the mechanical changes in collagen tissues across hierarchical scales from molecular, to fiber, to tissue-levels. We observed a linear increase in molecular spacing (from 1.45nm to 1.5nm) and a decrease in the D-period length (from 67.5nm to 67.1nm) in aged tissues, both using the ribose model of in vitro glycation and in native human probes. Multiscale mechanical analysis of in vitro glycated tendons strongly suggests that AGEs reduce tissue viscoelasticity by severely limiting fiber-fiber and fibril-fibril sliding. This study lays an important foundation for interpreting the functional and biological effects of AGEs in collagen connective tissues, by exploiting experimental models of AGEs crosslinking and benchmarking them for the first time against endogenous AGEs in native tissue.