a hot topic of research and debate.
Like dietary restriction, resveratrol has long
been known to have interesting properties.
During the 1990s it was extensively studied
as a potential link between improvements in
a variety of health indicators and moderate
consumption of red wine
. The antioxidant
properties of resveratrol, in particular, have
been suggested to account for many of its ben-
eficial properties, including putative cardio-
protective and anticancer activities, as well as
providing protection against liver failure. Here
it is noteworthy that Baur et al.
show that res-
veratrol has a profound ability to prevent liver
damage associated with the high-fat diet.
Resveratrol became of particular interest
to gerontologists with the report
that it can
increase lifespan in yeast by activating particu-
lar enzymes (protein deacetylases) of the Sir2
family of proteins (sirtuins). Sirtuins are evo-
lutionarily conserved mediators of long evity
that might also play a role in lifespan exten-
sion through dietary restriction
. Although the
results from the initial study of resveratrol in
yeast remain controversial
, subsequent work
has suggested that resveratrol has modest
effects on lifespan in both worms and flies
and a more substantial effect on lifespan in a
. Based on these findings, it
has been proposed that resveratrol increases
lifespan in several different organisms by a
mechanism similar to dietary restriction
Baur et al.
favour the view that many
(perhaps all) of the beneficial properties of
resveratrol are the result of increased sirtuin
activity, and various studies have supported
the idea that sirtuins underlie the effects attrib-
uted to resveratrol in vivo
. However, there is
a surprising lack of biochemical evidence that
resveratrol directly increases sirtuin-mediated
deacetylation of biologically relevant sub-
strates, and some evidence that it may not
Resveratrol is also known to interact with
numerous proteins and pathways, including
mitochondrial ATP synthase and complex
III, fatty-acid synthase, protein kinase C, p53,
MEK1, TNF-Ȋ and NF-ȔB, all of which are
candidates for mediating its in vivo effects. In
particular, activation of AMP kinase by resvera-
trol protects against atherosclerosis and liver
damage in diabetic mice
, suggesting a likely
mechanism for the observations reported by
Baur and colleagues.
Given the available data, it is difficult to
predict the answers to a few key questions.
Will resveratrol have an effect on health and
longevity in mice fed a standard diet, rather
than a high-calorie diet? Will it be effective in
mice with genetic backgrounds other than the
inbred strain used in the current report? Will
it be effective in humans? Studies addressing
these questions are under way: the answers will
go some way towards determining whether or
not resveratrol is a bona fide dietary-restric-
Many people will wonder whether they
should start supplementing their diets with
resveratrol. After all, it is generally regarded
as safe, and can be purchased over the Inter-
net with promises of improved health and
longevity. Our advice is to exercise caution.
The safety of resveratrol at the high doses in
humans comparable to those used by Baur
is unknown, especially over the course of
years or even decades, when relatively modest
side effects could have dramatic consequences.
A logical next step would be to initiate con-
trolled studies to find out whether resveratrol
can safely reduce the ill-effects associated with
diabetes or obesity in humans.
In the most optimistic assessment, a true
mimetic of dietary restriction could be effective
against many age-associated human diseases,
including heart disease, diabetes, cancer and
neurological disorders such as Alzheimer’s dis-
ease. Even if resveratrol doesn’t make the grade,
it is not the last hope of gerontologists, or nec-
essarily even the best. Studies of several other
compounds are under way in multi centre stud-
ies of mouse ageing sponsored by the National
Institute on Aging
. These include potent
antioxidants and compounds targeting other
pathways thought to influence lifespan exten-
sion through dietary restriction.
For now, we counsel patience. Just sit back
and relax with a glass of red wine — which,
alas, has only 0.3% of the relative resveratrol
dose given to the gluttonous mice (note also
that increasing the dose via wine will not be
healthy). But if you must have a Big Mac, fries
and apple pie, we may soon know if you should
supersize that resveratrol shake. ■
Matt Kaeberlein and Peter S. Rabinovitch are
in the Department of Pathology, University of
Washington, Seattle, Washington 98195, USA.
1. Baur, J. A. et al. Nature 444, 337–342 (2006).
2. Soleas, G. J., Diamandis, E. P. & Goldberg, D. M. Clin.
Biochem. 30, 91–113 (1997).
3. Howitz, K. T. et al. Nature 425, 191–196 (2003).
4. Longo, V. D. & Kennedy, B. K. Cell 126, 257–268
5. Kaeberlein, M. et al. J. Biol. Chem. 280, 17038–17045
6. Wood, J. G. et al. Nature 430, 686–689 (2004).
7. Valenzano, D. R. et al. Curr. Biol. 16, 296–300 (2006).
8. Baur, J. A. & Sinclair, D. A. Nature Rev. Drug Discov. 5,
9. Borra, M. T., Smith, B. C. & Denu, J. M. J. Biol. Chem. 280,
10. Zang, M. et al. Diabetes 55, 2180–2191 (2006).
Spinning discs in the lab
Steven A. Balbus
What causes gas to be drawn in towards black holes, rather than remain in a
stable orbit as planets do around the Sun? A laboratory result indicates that
something more than just hydrodynamics must be at work.
On page 343 of this issue, Ji et al.
meticulous experiment in which they confined
water between two independently turning
cylinders. Through artful experimental design,
the authors were able to reduce viscous effects
in the resulting ‘Couette’ flow to a level of one
part in two million. They chose the veloci-
ties of the cylinders so that they would mimic
— and so compel the confined fluid to mimic
— so-called keplerian rotation, which is typi-
cal of astrophysical disks around black holes.
Here, velocity is inversely proportional to the
square-root of the distance from the centre of
The result was that nothing happened at all:
the fluid continued to rotate stably. But why
exactly do astrophysicists and fluid dynami-
cists find this apparently harmless result so
In the early 1970s, astrophysicists were strug-
gling with the exciting and controversial ques-
tion of whether black holes — objects whose
gravity is so great that nothing, not even light,
can escape once captured — were real
slightly earlier, a series of compact sources of
X-ray radiation had been discovered. One
model held that this radiation originated from
gas disks surrounding black holes in binary sys-
tems of close stars
and galactic nuclei
. This gas
would dissipate its energy as heat, and ultimately
X-ray radiation. Its angular momentum would
be transported outward, and the gas would spi-
ral inward towards the hole. By understanding
these ‘accretion disks’, astronomers hoped that
they would, in one fell swoop, both explain the
mysterious X-ray sources and prove that black
The existence of black holes and their accre-
tion disks is now widely accepted by both
theorists and observers. But understanding
the dynamics of accretion disks, in black holes
and in other types of system, has turned out
to be an extremely knotty problem. Why do
disks accrete at all? Why does gas in motion
around a massive centre not remain in a stable,
The problem is that energy dissipation and
angular-momentum transport are properties
of a viscous fluid, and the viscosity of the disk
gas is far too small to account for the angular-
momentum loss that leads to accretion. This
problem might be solved if a keplerian gas
NATURE|Vol 444|16 November 2006
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