Home' Technology Review : December 2005 January 2006 Contents Q&A
TECHNOLOGY REVIEW december 2005/january 2006
Lenny Guarente has spent much
of the last two decades patiently
chipping away at the genetic and
biochemical underpinnings of the ag-
ing process, an area of research often
plagued by extreme hyperbole and ex-
travagant claims. The MIT biologist
is particularly focused on one tantaliz-
ing clue: for about 70 years, research-
ers have known that rats tend to live
longer when fed a diet that is ade-
quate in nutrition but very low in cal-
ories. While biologists are still unsure
whether severe calorie restriction will
have the same antiaging e�ect on hu-
mans, Guarente believes he and his
fellow researchers have found the
genes and a mechanism responsible
for delaying the aging process—at least
in lower organisms.
TR: If all goes well with antiag-
ing research, what might be pos-
sible in ﬁve to 10 years?
Guarente: I hope in 10 years
that we are way down the road
of drug discovery in �nding com-
pounds that will deliver at least some
of the bene�ts of calorie restric-
tion. And I think SIR2 is going to
be one of the important targets that
we want to go after with drugs.
That’s a gene you have identiﬁed
as being involved in aging, isn’t it?
We de�nitely think it is involved
in the aging process. In particu-
lar, it seems to be involved in sens-
ing caloric intake and asserting
e�ects on cells to adjust life span.
We think calorie restriction is a tre-
mendous opportunity for us to inter-
vene pharmacologically and have a
positive impact on human health.
So people won’t be going on a spe-
cial diet to get the effects of calo-
rie restriction, they’ll take a drug?
I think so, because the amount of
calories you would be taking in to get
the bene�ts is rather a severe diet,
about 1,000 to 1,200 calories a day.
And most people who have tried this
diet �nd it unpleasant. It makes them
cold, it makes them hungry, they’re
irritable, and I think compliance
would be very di�cult. So, the idea is
to understand what this diet does in
an e�ort to develop drugs that would
hit at least some of the targets and
deliver at least some of the bene�ts.
You’re talking about treating spe-
ciﬁc diseases, not the aging process.
The big idea here is that there
is a close connection between
aging itself and diseases of aging.
If one had a favorable impact on
the underlying aging process, dis-
eases of aging would also be fore-
stalled. And those diseases would
include cancer, diabetes, cardiovas-
cular disease, and neurodegenera-
tive diseases—really major diseases
How did you ﬁnd this antiaging gene?
This gene came out of studies
of aging in yeast. We started those
studies in 1991, and the question
we wanted to answer was, Do yeast
cells age? And if they do, are there
one or a small number of genes that
are particularly important in dic-
tating the life span of these cells?
For four or �ve years we published
nothing because we were just bang-
ing away at the problem. It took
eight years before we could come to
the conclusion that this one gene,
SIR2, in�uenced the life span.
The gene also promotes longev-
ity in worms and fruit ﬂies. What
seems to be its common role?
The idea would be that when food
is scarce it is an advantage to be able to
recognize the scarcity and slow down
aging and reproduction, to postpone
reproduction for when food becomes
available again. And now there is some
evidence that this is in fact the case.
Is this also true in humans?
It is a good hypothesis that some-
thing like this will be true in mam-
mals. And there are hints. But I would
say there is no conclusive evidence
yet. But we know that the mamma-
lian version of SIR2, which is a gene
call SIRT1, has at least some of the
activity in cells that one would antici-
pate for a life-extending function.
What needs to be tested is whether it
a�ects aging in the whole organism.
How large is this effect of calo-
rie restriction on aging in rodents?
Studies show this diet could
extend life up to 50 percent. So,
it is pretty substantial. But there
are people out there claiming sci-
ence will allow people to live thou-
sands of years. I tend to believe that
is a lot of bunk. But the opportunity
we do have is nothing to sneeze at.
I think it is the major opportunity
that Mother Nature has given us to
intervene in the aging process. And
by intervene I mean not just to pro-
mote longevity but to �ght diseases
Other researchers are testing the
antiaging effects of calorie restric-
tion in monkeys, aren’t they?
Those studies have been going
on for some 15 years now. I know of
two studies, and both are reporting
that the diet induces the same physi-
ological changes as in rodents, which
is a very good indicator. There’s no
report yet on whether it makes the
monkey live longer, because that
data takes a long time to be available.
But I think we’ll know quite soon.
Is all the hype a good or bad
thing for antiaging research?
It cuts both ways. The good part is
where there is public interest, there
is funding available for the research.
The bad thing is that if the work
does get overhyped in the media it
raises false expectations. I get asked
a lot, “What is taking so long?”
The skinny on the fountain of youth
Links Archive October 2005 March April 2006 Navigation Previous Page Next Page