I was most interested to see Robert Bradbury's discussion back in
August on calorie restriction and slowing of the ageing rate
("Why does calorie restriction reduce the rate of ageing?").
FREE RADICALS AND AGEING?
My interest in ageing follows from the potential role
of free radical damage to cellular components as part of the
ageing process. It is known that metabolic processes
generate free radicals. Also, although the radical scavenging mechanisms
of the cell are quite efficient, it is likely that they are not
100% effective in preventing radical damage, as Robert discussed.
So in going to a a calorie-reduced diet, a lowering of metabolic
activity , and or a change to pathway(s) that produces less
radicals, might reduce the degree of this damage.
TRANSITION METALS AND FREE RADICAL FORMATION:
I posit an extension to the view of free radical involvement in ageing,
deriving from the interest of our lab in the metabolism of
the transition metal copper: that copper might stimulate ageing-related
radical formation in vivo.
It is well established that copper, and another transition metal, iron,
promote the production of free-radicals in vitro.
If we assume that damage to cellular DNA is at least partly responsible
for the ageing process, then copper is most interesting as it is known
in vitro to bind to DNA and cause radical induced damage to it. Some
data indicates that this damage induction also occurs in vivo. Co-agents
for the copper-induced damage in vitro include metabolic compounds, such as
reducing sugars (which help the copper recycle).
Cellular systems for handling copper will sequester most of
the metal from the potential to cause damage. However, it is tenable
that some low level of 'free' copper occurs in cells, due to the
affinity of copper for various cell components. So it can be proposed
that some of this metal is bound to the DNA.
Then, co-agents could act with copper to catalyze radical induced
damage to the cellular DNA. These co-agents might be metabolic
substrates or products, which are reduced in concentration under
a calorie restricted diet.
Finally, it is necessary to assume that the DNA repair systems of
the cell are not 100% efficient in rebuilding the damaged DNA
without error, at least under a non calorie restricted diet.
I would be glad of any comments on these ideas about the
possible involvement of copper in the ageing process.
School of Biological Sciences
University of Birmingham, U.K.