
Telomerase gene therapy in mice delays aging without increasing cancer (2012) - edward
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494070/
======
lvs
We're for some reason getting a lot of this stuff on HN, but it's not
surprising that there isn't much expertise to evaluate it here.

It's impossible to argue anything about cancer from this study. The mean
lifespan of this strain of mice is around two years, and natural cause of
death is not commonly due to tumor burden. Black 6 mice were bred for
atherosclerosis and hyperinsulinemia studies, and mortality is usually related
to diabetes and cardiovascular disease. Long story short: they die long before
unaided tumorigenesis is an issue.

------
reasonattlm
I'll make the same comment on this as before, which is that the lack of cancer
is the interesting outcome, and that there isn't yet a robust defensible
accounting of exactly why telomerase is extending life in these mice. For
example, effects on mitochondrial function that lower their damage rate over
time have been proposed as another activity for telomerase. It isn't beyond
the pale to think it as important as increased stem cell activity.

\------------

Telomeres are caps of repeated DNA sequences at the end of chromosomes. A
little telomere length is lost every time a cell divides and its DNA is
replicated, and this is one portion of the limiting mechanism that causes the
somatic cells that make up the overwhelming majority of tissues to divide only
a set number of times and then destroy themselves. Stem cells on the other
hand make use of the enzyme telomerase to add repeated DNA sections to the
ends of their telomeres as needed. They must maintain lengthy telomeres as it
is their job is to continually spin off new long-telomere somatic cells to
keep tissues running smoothly. This is a considerable simplification of the
actual situation, but it is good enough for this discussion. The important
point here is that if you measure average telomere length in a given tissue,
and immune cells from blood are the most commonly used for this purpose at the
moment, what you are in fact measuring is a some combination of present cell
replication rates, cell replenishment rates, and telomerase activity.

There is a statistically significant correlation between average telomere
lengths in immune cells and age and illness across a population. This isn't so
useful for any given individual looking at a number and trying to figure out
whether or not it means anything for future health, but it is true that the
older and more ill a person is, the more likely it is for average telomere
length in immune cells to be comparatively short. Is this meaningful to
efforts to extend life? That is a question worth asking twice, given that
telomere length measures look very much like a secondary marker resulting from
the characteristic decline of stem cell activity and tissue maintenance with
advancing age, and we really want to aim at primary causes rather then
secondary and later mechanisms.

Nonetheless, a fair number of researchers are interested in trying to lengthen
telomeres as a potential way to treat illness or lengthen life, and in recent
years one research group has used gene therapy to raise levels of telomerase
in mice. This turns out to extend mouse life span, with the caveats that (a)
short-lived mammals like mice actually have quite different telomere dynamics
from long-lived mammals such as we humans, so it is far from clear as to what
the same thing would do in people, and (b) it is by no means certain what
exactly is going on under the hood here. Is telomerase keeping somatic cells
alive for longer, it is increasing stem cell activity, is it perhaps
interacting with mitochondria in some way to reduce their contribution to
aging, or is some other as yet undiscovered mechanism is at work?

Researchers will come to a conclusion at some point, as there seems to be slow
but steady progress towards further investigations of telomerase gene therapy
in mice. The same group that pioneered this approach is now heading down the
traditional path of attempts to apply this treatment as a late stage
intervention for age-related disease and dysfunction. They do this because it
is still the only practical way to bring treatments to the clinic these days:
approaches are inevitably sidelined into marginal applications intended to be
applied after the damage is done. It is a ridiculous situation, and one that
causes immense damage to the pace of progress by diverting researchers away
from producing methods of prevention.

