Re: AGING: reversal of neuron functional declines

From: Robert J. Bradbury (
Date: Sat Oct 27 2001 - 22:49:56 MDT

Jeff asked the $100 question:

> Is there a causative correlated age-related reduction in on
> board nerve growth factor, which might be increased by some
> manner of stimulation (hormone therapy, gene therapy, other?),
> or is the nerve growth factor still at "youthful" levels but the
> neurons are no longer responding as before to those levels,
> needing more NGF to achieve the higher "youthful" level of response?

It is generally accepted that protein synthesis declines with
age. NGF is, I believe, a peptide growth factor, so "presumably"
its synthesis declines with age as well (as is the case with
Growth Hormone and many other hormones). Now, of course the
"receptors" for the hormones are transmembrane proteins and
the signaling factors that transmit the signal indicating
the "reception" of a hormone to the nucleus (generally altering
gene expression) are proteins also. So this turns into a chicken and
egg problem as to whether the cause is due to a decline in hormone
production levels or a decline in the receptors and signaling factors.
Most probably it is both. In the well studied case of insulin and
insulin receptors (probably hundreds of papers), I'm unsure as to
whether there is any conclusive evidence for pointing the
finger of blame for "insulin resistance" at the production of the
hormone or the failure to receive and/or transmit the signal properly.
(I'll admit I haven't studied this specific problem for a couple of
years though so our understanding may have improved.)

This problem further complicated by a loss in neuron number with age.
Since it does not appear that there are feedback loops to
up-regulate hormone synthesis when amounts are low one would
expect a decline in hormone levels independent of whether or
not the cells become less efficient at protein synthesis with age.
The good part about the article is that it suggests that the
receptor and intracellular signal pathways are sufficiently
intact to respond to the signals if we can administer them.

Regarding species differences in nerve growth factor -- I expect
they are relatively highly conserved (most hormones are). I'm
moderately sure you could look them up in SwissProt for a detailed
check (though there is always some chance that the Rhesus monkey
genes haven't been cloned yet).


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