Hi Paul,

In the August 2, 2008 issue of Science News, as referenced on their
website at

http://www.sciencenews.org/view/generic/id/33832/title/Fountain_of_Yo
uth%2C_with_caveats

they refer to the research below (PUBMED abstract) as indicating
that resveratrol may have a downside affect on the brain in terms of
increasing oxidative sensitivity. Since I don't have access to the
full article, I can't tell if there are any deficiencies in the
experiment or its interpretation. However, I could say that for
those of us who are life extension oriented, we are probably taking
enough neurological antioxidants to compensate.

Cell Metab. 2008 Jul;8(1):38-48.
SirT1 inhibition reduces IGF-I/IRS-2/Ras/ERK1/2 signaling and protects
neurons.
Li Y, Xu W, McBurney MW, Longo VD.
Neuroscience Program, University of Southern California, Los Angeles,
CA 90089-2520, USA.

Sirtuins are known to protect cells and extend life span, but our
previous studies indicated that S. cerevisiae Sir2 can also increase
stress sensitivity and limit life-span extension. Here we provide
evidence for a role of the mammalian Sir2 ortholog SirT1 in the
sensitization of neurons to oxidative damage. SirT1 inhibition
increased acetylation and decreased phosphorylation of IRS-2; it
also reduced activation of the Ras/ERK1/2 pathway, suggesting that
SirT1 may enhance IGF-I signaling in part by deacetylating IRS-2.
Either the inhibition of SirT1 or of Ras/ERK1/2 was associated with
resistance to oxidative damage. Markers of oxidized proteins and
lipids were reduced in the brain of old SirT1-deficient mice, but
the life span of the homozygote knockout mice was reduced under both
normal and calorie-restricted conditions. These results are
consistent with findings in S. cerevisiae and other model systems,
suggesting that mammalian sirtuins can play both protective and
proaging roles.

PMID: 18590691


Terry