Lou Pagnucco wrote:
> Telomerase May Protect Nerve Cells from Brain Disorders
Very interesting, potentially. The well-established acceleration of
telomere shortening by oxidative stress in vitro (von Zglinicki's
work, among others) certainly suggests that telomerase should slow
telomere shortening in highly-stressed postmitotic cells as well as
in rapidly-dividing ones. Mattson's earlier work found an anti-
apoptotic role for telomerase in cancer cells (J. Biol. Chem. 274:
7264); similar reports exist from other groups.
However...
The thrust of this news report (though maybe not the actual article,
which I haven't seen) is that apoptosis of neurons is a causative
step in development of Alzheimer's pathology, such that inhibiting
apoptosis would be therapeutic. This is an example of the general
assumption that apoptosis is bad for us, which is usually wrong --
in general, apoptosis SLOWS DOWN aging and age-related pathologies
by eliminating cells that are causing the pathologies. Retarding
that sort of apoptosis would therefore exacerbate the pathology.
So, is neuronal apoptosis in AD good or bad? In fact, does it
happen at all? A very instructive letter to Science from George
Perry and colleagues (Science 282:1265) explains the problem. Here
is the start of it:
An article ... presents the case for apoptotic neuronal death in
Alzheimer's disease (AD) based on culture studies and histological
analyses. We strongly disagree that this evidence supports
widespread apoptosis in AD. Apoptosis requires only 16 to 24 hours
for completion and, therefore, in a chronic disease like AD with an
average duration of almost 10 years, less than one in about 4000
cells should be undergoing apoptosis at any given time (that is,
observation of apoptotic events should be rare). Indeed, if all the
neurons reported with DNA cleavage were undergoing apoptosis, the
brain would rapidly be stripped of neurons. This is certainly not
the case in AD.
The conclusion is that AD neurons may exhibit some of the hallmarks of
apoptosis because they initiate apoptosis but then arrest it. Similar
features are seen in muscle fibre segments that have accumulated mtDNA
mutations (see e.g. Mirabella et al, Brain 123:93).
In conclusion: there is more to this topic than meets the eye.
Aubrey de Grey
