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

J Biol Chem. 2020 Jul 31;295(31):10562-10571. doi: 10.1074/jbc.RA119.011031. Epub 2020 May 7.


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.

Keywords: aging; chemistry; collagen; connective tissue; cross-links; diabetes; lysine glycation; mechanical stress; physical strain; protein cross-linking; tendon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Collagen / metabolism*
  • Glycosylation
  • Mice
  • Tail / metabolism*
  • Tendons / metabolism*


  • Collagen