Cell regeneration and necrosis

[mktsgm]

TL;DR Summary

If every cell can regenerate why do we have to worry about inflammatory diseases and necrosis?

It is common knowledge that cells in our body regenerate. Every cell, except perhaps neurons, has a definite life-span. When cells die due to programmed cell death like apoptosis it is welcomed as cells are understood to be regenerating itself.

If so why do we have to worry about inflammatory diseases (which cause cellular and tissue level cell death) and necrosis? After all, cells are programmed to regenerate itself when sufficient numbers are not there in a tissue. So sooner or later, the tissue will be back to its normal cell count. Do we have to fear diseases then?

Of course, there can be a limit to the number of times a cell can regenerate and regrow. If we have sufficient balance in regrowth, do we have to worry about infection, inflammation or necrosis?

Or maybe, I am missing some crucial factors to consider. Please enlighten me.

Thanks in advance.

 

[sysprog]

There's something loosely called the 'mitotic clock' that limits the number of times a cell can regenerate. At the ends of each of the chromosomes of fully differentiated cells there is a fixed-length sequence consisting of TTAGGG sections which is repeated in human beings about 70 times for most cells. These sequences are called telomeres. Mitosis is unable to replicate the very ends of linear DNA, so the daughter cells have shorter telomeres.

After about 70 generations, the telomere is depleted, and the ends of the chromosomes splay out,, and DNA that codes for proteins is attacked by intracellular acids, causing the cell to emit caspases, which signals the start of the apoptosis ensuing resulting process.

Stem cells are an exception to this, because they retain the capability to produce telomerase, an enzyme which by means of its mRNA subunit presents a template for rebuilding the guanine-rich TTAGGG repeated sequence.

When rogue cells get telomerase capability from migratory mesenchymal stem cells it's problematic. If the rogue cells have oncogenes, they be transfected into the stem cells, which can then transfer them to other cells in the vicinity of cells that are emitting peptide signals, and so mediate metastasis of neoplastic growth. But that's another topic. You're apparently asking about ordinary senescence.

Please bear in mind also that free radicals can, by damaging cells, necessitate cell replacement, and thereby speed up the mitotic clock, and that's one of several strong contributors to overall aging.

Here's an open article on telomere biology: https://science.sciencemag.org/content/sci/350/6265/1193.full.pdf

 

[BillTre]

Not all cells in a tissue will ever divide again.
Some are terminally differentiated.

Those cell will get replaced over time by derivatives of stem cells that are closely related (in the genes they express and the overall state the cell is on), They are often nearby spatially, but not where the differentiated cells are doing their work.

Examples might be skin cells: terminally differentiated, stem cells below the skin cells (different cell type with different set of genes expressed) and will divide when new cells are needed for replacement purposes.
the cells lining the GI tract are another example.