With apologies to my esteemed friends, here are a few thoughts I have had regarding the proposal of plasma exchange. They will probably be quite laughable but I welcome your constructive comments.
The work by
Amy Wagers and Irina Conboy and others gives us tantalising hope that exchanging
old plasma for young may help rejuvenate at least some tissues of the human body.
the example of a kidney transplanted from an old donor to a young recipient is
the closest we have to a rejuvenation “experiment”, it is a flawed experiment
as the donated kidneys are subjected to sustained attack by the host immune
system (albeit dampened by drugs.)
In a recent
experiment, Shytikov et al (2014) failed to extend the lifespan of mice beyond
controls with frequent injections of plasma from young mice. One possible
explanation for that result is as follows:
that aging is caused by an imbalance of plasma-borne factors (that is; some
present in excess, a paucity of others), the aim of the plasma exchange would
be to rebalance the factor profile to that of a young mouse.
levels of a factor may be due to lower transcription rates, lower translation
rates, post-translational modification, inactivation, receptor binding, higher
excretion rates or other unidentified reasons.
higher plasma levels of a factor may be due to higher transcription or translation
rates, receptor scarcity or receptor inactivation, loss of inhibiting factors, lower
rates of excretion or still other unknown reasons.
introduced to the old animal should begin to have effects almost immediately,
but, conversely, the old body will be “working” to return the plasma to
another plasma exchange will be necessary well prior to this stage in order to
maintain the effect. (In other words, to mimic as closely as possible
hetereochronic parabiosis, a continuous process.)
possible explanation for the result is that the exchange volume was too little
and not often enough.
consider, also, that mice age many times faster than humans, so it is possible
that their “control mechanisms” drift from optimal levels much faster than those of humans. (Conversely, as humans age much more slowly than mice, perhaps plasma transfusions will be more effective in slowing aging?)
One way to
explore this might be to identify the factors that give the most “weight” to
aging in humans and then measure their typical rates of production and
destruction. This might allow an estimate of the minimum period between plasma
exchanges to be calculated.
Shytikov, D., Balva, O., Debonneuil,
E., Glukhovskiy, P. and Pishel, I.
Aged Mice Repeatedly Injected with
Plasma from Young Mice:
A Survival Study. BioResearch Open
AccessVolume 3, Number 5, October 2014.