Exogenous Collagen Cross-linking Reduces Scleral Permeability: Modeling the Effects of Age-Related Cross-link Accumulation

2009 ◽  
Vol 50 (1) ◽  
pp. 352 ◽  
Author(s):  
Jay M. Stewart ◽  
David S. Schultz ◽  
On-Tat Lee ◽  
Monique L. Trinidad
Keyword(s):  
Cross Linking ◽  
Cross Link ◽  
Permeability Modeling ◽  
Age Related ◽  
Collagen Cross Linking

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

2020 ◽  
Vol 295 (31) ◽  
pp. 10562-10571 ◽  
Author(s):  
Melanie Stammers ◽  
Irina M. Ivanova ◽  
Izabella S. Niewczas ◽  
Anne Segonds-Pichon ◽  
Matthew Streeter ◽  
...  
Keyword(s):  
The Other ◽  
Cross Linking ◽  
Structural Protein ◽  
Cross Link ◽  
Age Related ◽  
Cross Links ◽  
Tail Tendon ◽  
Collagen Cross Linking ◽  
Age Related Changes ◽  
Tendon Collagen

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.

scholarly journals Chemistry of collagen cross-linking: biochemical changes in collagen during the partial mineralization of turkey leg tendon

1997 ◽  
Vol 322 (2) ◽  
pp. 535-542 ◽  
Author(s):  
Lynda KNOTT ◽  
John F. TARLTON ◽  
Allen J. BAILEY
Keyword(s):  
Collagen Matrix ◽  
Cross Linking ◽  
Cross Link ◽  
Lysine Residues ◽  
Collagen Mineralization ◽  
Cross Links ◽  
The Cross ◽  
Calcified Tissues ◽  
Turkey Leg Tendon ◽  
Collagen Cross Linking

With age, the proximal sections of turkey leg tendons become calcified, and this phenomenon has led to their use as a model for collagen mineralization. Mineralizing turkey leg tendon was used in this study to characterize further the composition and cross-linking of collagen in calcified tissues. The cross-link profiles of mineralizing collagen are significantly different from those of other collagenous matrices with characteristically low amounts of hydroxylysyl-pyridinoline and the presence of lysyl-pyridinoline and pyrrolic cross-links. However, the presence of the immature cross-link precursors previously reported in calcifying tissues was not supported in the present study, and was found to be due to the decalcification procedure using EDTA. Analysis of tendons from young birds demonstrated differences in the cross-link profile which indicated a higher level of hydroxylation of specific triple-helical lysines involved in cross-linking of the proximal tendon. This may be related to later calcification, suggesting that this part of the tendon is predestined to be calcified. The minimal changes in lysyl hydroxylation in both regions of the tendon with age were in contrast with the large changes in the cross-link profile, indicating differential hydroxylation of the helical and telopeptide lysine residues. Changes with age in the collagen matrix, its turnover and thermal properties in both the proximal and distal sections of the tendon clearly demonstrate that a new and modified matrix is formed throughout the tendon, and that a different type of matrix is formed at each site.

scholarly journals Long-Term Exercise Training Attenuates Age-Related Diastolic Dysfunction: Association of Myocardial Collagen Cross-Linking

2009 ◽  
Vol 24 (1) ◽  
pp. 32 ◽  
Author(s):  
Su-Yeon Choi ◽  
Hyuk-Jae Chang ◽  
Sang-Il Choi ◽  
Kwang-Il Kim ◽  
Yong-Seok Cho ◽  
...  
Keyword(s):  
Exercise Training ◽  
Diastolic Dysfunction ◽  
Cross Linking ◽  
Age Related ◽  
Myocardial Collagen ◽  
Collagen Cross Linking

Collagen stability and cross-linking in normal and kyphoscoliotic mouse intervertebral discs

1988 ◽  
Vol 8 (4) ◽  
pp. 315-322 ◽  
Author(s):  
Gillian Venn ◽  
Trevor Sims ◽  
Roger M. Mason
Keyword(s):  
Extracellular Matrix ◽  
Gene Mutation ◽  
Muscle Atrophy ◽  
Intervertebral Discs ◽  
Cross Linking ◽  
Extrinsic Factor ◽  
Thoracic Region ◽  
Cross Link ◽  
Collagen Stability ◽  
Collagen Cross Linking

Intervertebral discs of the cervical-thoracic region of the spine of BDL mice which are homozygous for the ky gene mutation undergo degeneration. Discs from these mice have a normal collagen content and undergo normal collagen cross linking prior to the appearance of degenerative changes. The major reducible collagen cross-link formed in discs of these mice and in normal CBA strain mice is hydroxylysino-5-ketonorleucine. These results and other previous results indicate that the discs in the ky mouse develop degenerative disease due to an extrinsic factor rather than to an intrinsic abnormality of their extracellular matrix. The extrinsic factor has been identified as spinal muscle atrophy.

scholarly journals Mechanism of protein cleavage at asparagine leading to protein–protein cross-links

2019 ◽  
Vol 476 (24) ◽  
pp. 3817-3834 ◽  
Author(s):  
Michael G. Friedrich ◽  
Zhen Wang ◽  
Kevin L. Schey ◽  
Roger J. W. Truscott
Keyword(s):  
Bond Cleavage ◽  
Peptide Bond ◽  
Human Lens ◽  
Cross Linking ◽  
Protein Cleavage ◽  
Cross Link ◽  
Peptide Bond Cleavage ◽  
Age Related ◽  
Αb Crystallin ◽  
Cross Links

Long-lived proteins (LLPs) are present in numerous tissues within the human body. With age, they deteriorate, often leading to the formation of irreversible modifications such as peptide bond cleavage and covalent cross-linking. Currently understanding of the mechanism of formation of these cross-links is limited. As part of an ongoing study, proteomics was used to characterise sites of novel covalent cross-linking in the human lens. In this process, Lys residues were found cross-linked to C-terminal aspartates that had been present in the original protein as Asn residues. Cross-links were identified in major lens proteins such as αA-crystallin, αB-crystallin and aquaporin 0. Quantification of the level of an AQP0/AQP0 cross-linked peptide showed increased cross-linking with age and in cataract lenses. Using model peptides, a mechanism of cross-link formation was elucidated that involves spontaneous peptide bond cleavage on the C-terminal side of Asn residues resulting in the formation of a C-terminal succinimide. This succinimide does not form cross-links, but can hydrolyse to a mixture of C-terminal Asn and C-terminal Asp amide peptides. The C-terminal Asp amide is unstable at neutral pH and decomposes to a succinic anhydride. If the side chain of Lys attacks the anhydride, a covalent cross-link will be formed. This multi-step mechanism represents a link between two spontaneous events: peptide bond cleavage at Asn and covalent cross-linking. Since Asn deamidation and cleavage are abundant age-related modifications in LLPs, this finding suggests that such susceptible Asn residues should also be considered as potential sites for spontaneous covalent cross-linking.

Age Related Fibrosis Is Improved by Reducing Collagen Cross-Linking With Lysyl Oxidase Inhibition

2013 ◽  
Vol 29 (10) ◽  
pp. S247
Author(s):  
N. Rosin ◽  
M. Sopel ◽  
A. Falkenham ◽  
T. Myers ◽  
T.D. Lee ◽  
...  
Keyword(s):  
Lysyl Oxidase ◽  
Cross Linking ◽  
Age Related ◽  
Oxidase Inhibition ◽  
Collagen Cross Linking

scholarly journals Collagen cross-linking in human bone and articular cartilage. Age-related changes in the content of mature hydroxypyridinium residues

1988 ◽  
Vol 252 (2) ◽  
pp. 495-500 ◽  
Author(s):  
D R Eyre ◽  
I R Dickson ◽  
K Van Ness
Keyword(s):  
Cortical Bone ◽  
Cancellous Bone ◽  
Human Subjects ◽  
Adult Life ◽  
Bone Collagen ◽  
Cross Linking ◽  
Cross Link ◽  
Age Related ◽  
Cross Links ◽  
And Cartilage

The concentration in collagen of hydroxypyridinium cross-linking amino acids was measured in samples of bone and cartilage from human subjects aged from 1 month to 80 years. Cortical and cancellous bone samples were dissected and analysed separately. In both bone and cartilage, the content of this mature form of cross-link reached a maximum by 10-15 years of age (the amount in cartilage being 5-10 times that in bone), then stayed essentially in the same range throughout adult life. In bone the ratio of the two chemical variants of the mature cross-link, hydroxylysylpyridinoline to lysylpyridinoline, was constant throughout adult life at 3.5:1, whereas in cartilage it was always greater than 10:1. The ratio of hydroxypyridinium cross-links to borohydride-reducible keto-amine cross-links also changed with age. The reducible cross-links in bone collagen decreased steeply in content between birth and 25 years, but persisted in significant amounts throughout adult life. Reducible cross-links had virtually disappeared from cartilage by 10-15 years of age, being replaced by hydroxypyridinium residues, their maturation products. Cancellous and cortical bone collagens showed similar trends with age in their content of mature cross-links, though for each subject the concentration in cancellous bone was always lower than in cortical bone, presumably reflecting the higher turnover rate and hence the more immature state of cancellous bone.

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