Caloric restriction and mitochondrial fatty acid composition

Aubrey de Grey ag24 at mole.bio.cam.ac.uk
Wed Jan 20 08:25:18 EST 1999


Hi Paul,

> Has anyone paid much attention to the fatty acid compositions of
> calorie-restricted diets?

Best I know of is Mech Ageing Dev 48(3):207-19 from 1989, which found
that CR *decreases* unsaturation.  This was confirmed in 1993 (Mech
Ageing Dev 72(2):155-63).   Walter Cefalu presented some very intriguing
work at the Gerontological Society meeting in 1997 indicating that CR
increases levels of (the extremely unsaturated) docosahexaenoic acid,
but it doesn't seem to have appeared in print.

> The polyunsaturated FA content of the mitochondrial inner membrane
> correlates with its proton leak (and may be causal?).

Yes -- probably because of its increased oxidisability (e.g. van Zutphen
and Cornwell, J Membr Biol 1973; 13:79-88; Ivanov et al, Biophysics 1977;
22:644-648).

> It has been suggested that proton leak serves as a sink for redox
> energy to prevent ROS production by the respiratory chain.

Indeed.  :-)

> Less saturates = more polyunsaturates = higher proton leak = less ROS =
> slower ageing.

I think the most comprehensive destruction of that theory is probably a
rather recent paper, Pamplona et al, J Lipid Res 1998 Oct;39(10):1989-94.
Title: "Mitochondrial membrane peroxidizability index is inversely related
to maximum life span in mammals".  This follows up on a 1996 study from
the same group: Mech Ageing Dev 86(1):53-66, "Low fatty acid unsaturation
protects against lipid peroxidation in liver mitochondria from long-lived
species: the pigeon and human case".

Aubrey de Grey




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