Age-related changes in the physical properties, cross-linking, and glycation of collagen from mouse tail tendon

Melanie Stammers,Irina M Ivanova,Izabella S Niewczas,Anne Segonds-Pichon,Matthew Streeter,David A Spiegel,Jonathan Clark

doi:10.1074/jbc.ra119.011031

Melanie Stammers, Irina M Ivanova + Show 5 more

Open Access

https://doi.org/10.1074/jbc.ra119.011031

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Abstract

Collagen is a structural protein whose internal cross-linking critically determines the properties and functions of connective tissue. Knowing how the cross-linking of collagen changes with age is key to understanding why the mechanical properties of tissues change over a lifetime. The current scientific consensus is that collagen cross-linking increases with age and that this increase leads to tendon stiffening. Here, we show that this view should be reconsidered. Using MS-based analyses, we demonstrated that during aging of healthy C57BL/6 mice, the overall levels of collagen cross-linking in tail tendon decreased with age. However, the levels of lysine glycation in collagen, which is not considered a cross-link, increased dramatically with age. We found that in 16-week-old diabetic db/db mice, glycation reaches levels similar to those observed in 98-week-old C57BL/6 mice, while the other cross-links typical of tendon collagen either decreased or remained the same as those observed in 20-week-old WT mice. These results, combined with findings from mechanical testing of tendons from these mice, indicate that overall collagen cross-linking in mouse tendon decreases with age. Our findings also reveal that lysine glycation appears to be an important factor that contributes to tendon stiffening with age and in diabetes.

Highlights

Collagen is a structural protein whose internal cross-linking critically determines the properties and functions of connective tissue
The general consensus is that as collagen ages there is an increase in the stiffness with loss of elasticity and that this is due to an increase in covalent intermolecular cross-linking between collagen molecules which develops with age [1]
The collagen cross-links can be divided into two groups, those that are of enzymatic origin and those that form through purely chemical reactions with reactive molecules perfusing the tissues

Summary

Introduction

Collagen is a structural protein whose internal cross-linking critically determines the properties and functions of connective tissue. We found that in 16-week-old diabetic db/db mice, glycation reaches levels similar to those observed in 98-week-old C57BL/ 6 mice, while the other cross-links typical of tendon collagen either decreased or remained the same as those observed in 20week-old WT mice. These results, combined with findings from mechanical testing of tendons from these mice, indicate that overall collagen cross-linking in mouse tendon decreases with age. While there has been disagreement [5, 6] with respect to the exact chemical structure that the analyzed compound represents within collagen, for the purposes of this publication it can be considered an indicator of aldol cross-links present in collagen before analysis

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