Magnus Lynch wrote:
> This article was published in this November's edition of Nature.
> "The p66shc adaptor protein controls oxidative stress response and
> life span in mammals"
Today's, to be precise: Nature 402:309-313. This is a sensational
result, even taking into account the small numbers of mice involved
(~15 each of mutant and controls) and the probably rather inexact
measurements of caloric intake of the mutants, which is always what
one looks at first when assessing a lifespan study. (This issue is
addressed only by the statement that "no statistically significant
differences were found in body weight and food consumption": no
methods of measurement, let alone data, are shown.) It was rather
poor of Nature to allow the authors to state in the abstract that
"no genes are known to increase individual life span" in mammals,
since the first such finding, in the dwarf mouse, was published in
Nature (1996, 384:33). But, as Guarente notes in the accompanying
"news & views" article (p243), dwarf mice are a good deal smaller
than wild-type whereas these mice are not.
The question of mechanism is clearly up for intense debate. The
authors found no obvious deleterious phenotype, but most people
will take the view that there surely is one (such as reduction of
fertility, maybe) until there is very compelling contrary data.
Two mechanisms are proposed in Guarente's article; many more are
conceivable. But the linkage between increased stress resistance
and increased lifespan is no surprise, since it is seen in many
invertebrate mutants and also in mice with caloric restriction.
Said that way, the new result is only a combination of those two
previous ones, but that doesn't detract from its significance.
I'm not too sure about Richard's proposal -- I think replacement
of cells may not be too relevant, because aging so badly affects
postmitotic cells which are not substantially replaced. Probably
more likely is that the loss of ability to induce apoptosis is a
problem for mitotically competent cells, stopping it from getting
rid of damaged cells, which therefore requires up-regulation of
systemic antioxidant defences, thus fortuitously protecting the
non-dividing cells too. But I stress that that's pure conjecture,
because levels of resistance to oxidative stress were measured
only in terms of cell survival, not in terms of antioxidant or
repair enzyme levels.
The timing of publication is convenient, since the annual meeting
of the Gerontological Society of America starts tomorrow. I expect
to be able to report a good deal more on this topic on my return
Aubrey de Grey