Well, just when we thought things couldn't go any faster...
"Extended Life-Span Conferred by Cotransporter Gene Mutations
in Dosophila", B. Rogina, R. A. Reenan, S. P. Nilsen, S. L. Helfand,
Science 290(5499):2137-2140 (Dec. 15, 2000).
http://www.sciencemag.org/cgi/content/full/290/5499/2137
Abstract:
"Aging is genetically determined and environmentally modulated. In a study
of longevity in the adult fruit fly, Drosophila melanogaster, we found
that five independent P-element insertional mutations in a single gene
resulted in a near doubling of the average adult life-span without a
decline in fertility or physical activity. Sequence analysis revealed
that the product of this gene, named Indy (for I'm not dead yet), is
most closely related to a mammalian sodium dicarboxylate cotransporter--a
membrane protein that transports Krebs cycle intermediates. Indy was most
abundantly expressed in the fat body, midgut, and oenocytes: the principal
sites of intermediary metabolism in the fly. Excision of the P element
resulted in a reversion to normal life-span. These mutations may create
a metabolic state that mimics caloric restriction, which has been shown
to extend life-span."
The mean lifespan extensions were from 37 to 70 days (47% increase) and
the maximum lifespans were increased from 79 to 100 days (22% increase).
[These were somewhat misquoted in the NY Times (see below)].
Commentary in Science:
"Old Flies May Hold Secrets of Aging", E. Pennisi
Science 290(5499):2048 (Dec. 15, 2000).
http://www.sciencemag.org/cgi/content/full/290/5499/2048
N.Y Times discussion (with some misinterpreations possibly):
http://www.nytimes.com/2000/12/15/science/15AGIN.html?printpage=yes
Best excerpt:
> "I was finding it extremely irritating," Dr. Helfand said. "We had
> already pretty much prepared our paper and we just needed to know
> when these flies were going to die. They kept living on and on.
> At some point, it occurred to us that maybe something is happening
> here that we should be paying attention to."
Duuhhh....
In all likelyhood (as the extensive commentary by researchers shows),
this may be a critical insight into one of the key mechanisms by
which caloric restriction acts to extend lifespan (essentially
this is a genetic mutation that "starves" cells). The article
seems to indicate however that further mutations in this direction
do not provide additional benefits (i.e. more starvation decreases
longevity). Nor is it clear whether mammals would benefit to
the same degree from similar mutations or genetic pathway
manipulations (bear in mind that there is a lot of evolutionary
pressure for Drosophila to live fast and die young, we may
already be living "slower").
Judy Campisi's comments (in the NY Times article), that this
may provide a path for caloric-restriction mimicing drugs is
open to question, for if you block the transporter with a drug
(the most likely first strike at this), the cells, esp. neurons
are still going to "feel" like they aren't being fed... You
probably need a two drug approach, one to block the transporter
so the cells are calorie restricted and another to convince
your neurons that, yes, you really have just had the most filling
meal in your life...
As a side note, I'll point out to those experimentalists among us
(should I name names, no, I think not, for they are the unsung
heros and I acknowledge them for their dedication) -- now that a
strain of flies exists with an extremely extended longevity, what
will be required is insights into what extends the longevity of a
strain with already extended longevity (ah yes, we must tighten
down the thumb screws while we drip water slowly onto the end of
your nose...) Conquering aging is going to be succession of efforts
figuring out the next part of the genetic program that is broken.
I will comment in a highly unusual (for me), "The glass is half-empty"
tone, by pointing out that -- THE FLIES STILL DIED! But if you are a
"the glass is half-full" type, then this is indeed very good news
as it gives a key molecular insight into a huge body of knowledge.
We now have a very big lever and a place to stand. :-)
Robert
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