Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue

Alfonso Gautieri, Fabian S. Passini, Unai Silván, Manuel Guizar-Sicairos, Giulia Carimati, Piero Volpi, Matteo Moretti, Herbert Schoenhuber, Alberto Redaelli, Martin Berli, Jess G. Snedeker

Research output: Contribution to journalArticlepeer-review


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 1.45. nm to 1.5. nm) and a decrease in the D-period length (from 67.5. nm to 67.1. nm) 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.

Original languageEnglish
Pages (from-to)95-108
Number of pages14
JournalMatrix Biology
Publication statusPublished - May 2017


  • Advanced glycation end-products
  • Aging
  • Collagen mechanics
  • Functional microscopy
  • Small-angle X-ray scattering

ASJC Scopus subject areas

  • Molecular Biology


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