Thanks for this reference. I agree that liver deterioration is not
causal in aging. However, genome multiplication seems to be an
adaptation in the heart and possibly other normally non-proliferating
tissues, to conditions such as oxidative stress and other genotoxic
damage, which may be causal in aging. An understanding of the mechanisms
of genome multiplication may illuminate aging mechanisms not only from
an academic perspective, but also from an anti-aging engineering one. In
other words, we may be able to regulate polyploidy as an anti-aging
strategy in tissues where it may not frequently occur, and which ARE
causal in aging. I wonder if liver failure in animals which have not
evolved polyploidy IS causative in their aging. Also, have similar
experiments to the one you cite been done with hearts or other organs?
Indeed, the most promising way to regulate polyploidy in the liver seems
to be through thyroid hormone, except that I'm not sure whether the
regulation is direct (by regulation of proteins involved in
cytokinesis), or indirect, by exerting a selective pressure on
hepatocytes, with the ones that randomly fail to divide their cytoplasm
enduring better (in the presence of TH and the ensuing metabolic
stress). One question I have for anyone, is:
If an endocrine hormone regulates a certain cellular response, and a
population of cells in a tissue is exposed to that hormone at
physiologic high dose, do ALL the cells (assuming they all have the
pathway for hormone action intact) exhibit that particular response? The
question can be broken down into 2:
1. Does the hormone "make it" to all the cells? Can the cells closest to
the blood vessels shield the ones further away?
2. If the hormone does bind a receptor in the cell, are there any known
stochastic pathways, so that some cells may still not show the final
response?
The reason is that TH only induces higher ploidy (and here I'm being
vague as to whether it is through acytokinesis inducing binucleates or
amitotic cytokinesis of binucleates inducing mononucleates of higher
ploidy class because I don't know which it is) in a small fraction of
the liver cells.
-Iuval
