cron-web.org

[A1CR]

It appears that CR may reduce specific brain tissue, but
enhance the
function of the remaining cells to perform better. "The
http://en.wikipedia.org/wiki/Supraoptic_nucleus houses one
of the most
http://en.wikipedia.org/wiki/IGF-1_Receptor rich cell
populations in the
hypothalamus and is best known for its release of the
neuropeptides
http://en.wikipedia.org/wiki/Oxytocin and
http://en.wikipedia.org/wiki/Vasopressin ..."

Yaghmaie F, Saeed O, Garan SA, Voelker MA, Gouw AM, Freitag
W, Sternberg H,
Timiras PS.
Age-dependent loss of insulin-like growth factor-1 receptor
immunoreactive
cells in the supraoptic hypothalamus is reduced in
calorically restricted
mice.
Int J Dev Neurosci. 2006 Oct 9; [Epub ahead of print]
PMID: 17034982

Both life-long caloric restriction (CR) and the
suppression of
insulin-like growth factor-1 (IGF-1) signaling reliably
extend the mammalian
lifespan. The neuroendocrine system, regulated by the
hypothalamus, remains
the most convincing site of action for both these modes of
life extension.
Yet, determining whether CR actions are mediated by the
modulation of
neuroendocrine IGF-1 signaling remains unclear. Of the
hypothalamic nuclei
that express the IGF-1 receptor (IGF-1R), the cells of the
supraoptic
nucleus (SON) display some of the most robust IGF-1R
expression. Taking
IGF-1R immunoreactivity as an index of sensitivity to IGF-1,
we counted
IGF-1R immunoreactive and non-immunoreactive cells in the
SON of
young-ad-libitum fed (young-Al, 6 weeks), old-ad-libitum fed
(Old-Al, 22
months), and old-calorie-restricted (Old-CR, 22 months)
female B6D2F1 mice.
An automated imaging microscopy system (AIMS) .... Results
show that while
the total number of cells in the SON of ad-libitum fed mice
does not change
significantly with aging, a significant reduction in IGF-1R
immunoreactive
cells does occur in ad-libitum fed mice with aging. In
contrast to this,
calorie restricted mice show both a decline in the total
number of cells and
IGF-1R immunoreactive cells in the SON with age, but with
the decrease in
the latter being notably attenuated when compared to the
degree of loss seen
in ad-libitum fed mice. Thus, while CR induces greater loss
in the total
number of cells in the SON with age, it reduces the degree
of age-dependent
loss seen in IGF-1R expressing cells. As a result, when
compared to Old-AL
mice, the SON of Old-CR mice displays a greater proportion
of IGF-1R cells
and thus possibly enhanced IGF-1 sensitivity with aging.

.... CR was initiated at 14 weeks of age at 10% restriction,
increased to
25% restriction at 15 weeks and finally to 40% restriction
at 16 weeks

... Cell counts generated from 36 cross-sections spaced at
regular intervals
every 10 µm spanning the entire SON, show a decline in the
number of IGF-1R
immunoreactive cells in SON with aging, irrespective of
diet. More
precisely, Old-Al mice exhibit a 35% decline, while Old-CR
mice exhibit a
30% decline in IGF-1R immunoreactive cells when compared to
young-Al mice, p
< 0.5 (Fig. 3). ... Old-CR mice show an 8% increase in the
average number of
IGF-1R immunoreactive cells in comparison to Old-Al mice,
but this
difference is statistically insignificant, p > 0.05. ...
although aging
results in the loss of IGF-1R cells, no significant
difference is detected
between young-Al and Old-Al mice when comparing the total
number of SON
cells, which consists of both IGF-1R immunoreactive and IGF-1R
non-immunoreactive cells. In contrast to this, CR mice
exhibited a 21%
decline in total cell numbers when compared to young-Al
mice. When compared
to their ad-libitum fed counterparts, Old-CR mice show a 21%
drop in total
stained cells, p < 0.05. This demonstrates that caloric
restriction actually
increases the total cell loss in the SON (Fig. 4). Thus,
caloric restriction
enhances total cell loss while selectively maintaining IGF-1
receptor
expressing cells. With this trend in mind, the data were
used to calculate
the percentage of IGF-1R cells in the total cell population
of the SON for
each group of mice (Fig. 5). The percentage of IGF-1R cells
in the SON for
young-Al, Old-Al, and Old-CR mice were 34, 20, and 30.6%,
respectively.
Thus, the calculated percentage of IGF-1R immunoreactive
cells in the SON of
Old-Al mice shows a 41% decline in comparison to young-Al
mice, while Old-CR
mice showed only a 10% decline in the percentage of IGF-1R
cells, nearly
unchanged from that of young-Al mice. ... Old-CR mice
maintain significantly
higher and youth-like calculated percentage of IGF-1R
immunoreactive cells
at 30.6%, in comparison to Old-Al mice at 22%, p < 0.05. ...

In summation, this investigation reveals the following
trends with respect
to normal versus aging:
(1) Normal aging results in a decline in IGF-1R
immunoreactive cells,
but no significant change in the number of IGF-1R
non-immunoreactive cells,
leading to decreased percentage of IGF-1R immunoreactive
cells in the SON
when compared to young mice.
(2) CR results in only a slight attenuation of IGF-1R
immunoreactive
cell loss with age, but induces the loss of IGF-1R
non-immunoreactive cells,
resulting in the maintenance of a greater percentage of IGF-1R
immunoreactive cells in the SON with age.

... Accepting IGF-1R immunoreactivity as an index of IGF-1
sensitivity and
the percentage of IGF-1R immunoreactive cells in the SON as
a measure of the
overall functional impact of IGF-1 signaling in the SON, the
conclusion one
may draw from this investigation is that CR appears to have
an activating or
at the very least, protective affect on IGF-1 signaling. ...
paradoxical
given ... that it is the loss-of-function mutations in
IGF-1R that prolong
the lifespan in species ranging from the nematode and fruit
fly to the mouse
[and] activating mutations in insulin and IGF-1 signaling
shorten lifespan
(Tatar et al., 2001 and Clancy et al., 2001). ...