Paul Brookes wrote:
> Anyone seen this paper?
Yes; I've also seen the "in this issue" paragraph on page ix in which a
somewhat over-zealous soul says that it all comes down to increased ROS
production at Complex II... Thankfully the article says no such thing.
> One interesting thing they propose is that the accumulation of advanced
> glycation end products (AGEs) is increased because the oxidative stress
> damages GAPDH ... Later on in the paper they say aldose reductase is
> reversibly inhibited by s-nitrosation, and that increased mt ROS would
> reduce the available NO ... But.... I was under the impression that
> GAPDH was inhibited by s-nitrosation too, so they're arguing opposite
> effects for 2 different proteins.
Maybe; you know this stuff better than me but my impression is that the
inhibition of GAPDH is rather complex. Biochem. J. 309:891 seems to say
that while NO inhibits GAPDH, superoxide stimulates that inhibition. I
infer that there may be an action of superoxide on GAPDH itself, whose
effect outweighs the elimination of NO by reaction with superoxide, and
maybe aldose reductase is not similarly affected by superoxide.
> Has anyone examined AGEs in animals with differnet ageing
> rates and mito ROS rates to see if there's a correlation.
Not together, as far as I know, but in addition to the large literature
showing that mitochondrial ROS production is lower in long-lived animals
there is a study from Monnier's lab showing that AGE accumulation varies
in the same way: PNAS 93:485.
Aubrey de Grey