Outside of the cell, you have the extracellular matrix.
“If you took all the matrix out of your body, you wold be left with a slurry of cells on the floor.”
“You are 70% matrix.”
“A tissue is like a building (ECM)… the actual people are the cell which are living in that tissue.”
“Collagen occupies about 50% of the matrix.”
“The physiology of us, as animals, is regulated by the sun.”
“Tendon… 90-95% matrix… they are a strong peripheral clock tissue.”
The building is the matrix…
- “We only build a building once and then we live in it.”
- “The matrix that you make, by the time you are 17, stays with you for life and you die with it.”
- “If you are making your collagen matrixes by the time you are 17, and then you never make them again, how do you maintain them?”
“3 million to 10 million movements per year… that’s an awful lot of exercise on a tendon that you will only ever make once.”
“97% of collagen is permanent.. but 3% of your total collagen isn’t permanent… you make it and you degrade it everyday.”
“That 3% that you make and you degrade everyday, is a sacrificial collagen”:
- You make it
- You cover the surfaces
- You exercise in the day and you damage that 3%
- It’s cleaned up at night
- You make new
- You coat again
“You are using those well-structured tissues well beyond their sell by date.”
“Your clock is making molecules to be damaged, to be sacrificed, to save those beautiful structures that you made when you were growing up.”
“If I put a big hole in that wall, my systems haven’t really evolved to repair it properly, it just throws bricks in there to fill the hole.”
“The tendon is like a rope but you’ve got millions of strands of collagen fibrils going through the tendon. When you break a critical number, you can rupture the whole tendon. If you break a few, you’ve still got a mechanically strong tendon.”
“You need to degrade it because if you didn’t, everyday you would be accumulating another 3% of your matrix and then your tissues would just grow and become stiffer and you don’t want that… in the end, it would cause major problems.”
“The tendon clock dampens and lengthens with age.”
“If you have a small amplitude, you start to have less efficient processes in the day and less efficient processes at night… and if you lengthen this plot (over 27-28 hours), tomorrow morning, it all starts again when the sun comes up. So you could be missing these nighttime activities (e.g., cleaning).”
“Aging could be, the fact that you are missing this maintenance clean up process in the day and as the decades go on, you accumulate that damage.”
“Is that really what you want? Do you want to be making more collagen? Or do you want to be making enough collagen and making sure that you take away that collagen before the next day starts?”
“What you want to maintain is this core… so the idea is that you would now coat it in a substance (collagen) that you can damage, you can repair, and you can take it away.”
“The work we’ve done in tendon has a lot of relevance to fibrosis where you become overwhelmed by collagen.”
Email Karl Kadler: karl.kadler@manchester.ac.uk
