MiFR: Might CLA accelerate aging?

Aubrey de Grey ag24 at mole.bio.cam.ac.uk
Sat Apr 1 14:32:42 EST 2000


Michael Rae wrote:

> A fair number of people are taking conjugated linoleic acid (CLA) for
> weight loss or anti-cancer purposes. CLA has been reported to increase
> metabolic rate (1). This is fine if your only concern is to shed pounds;
> howerver, for those who are taking it for health purposes,if what is
> increased is the whole-body SPECIFIC metabolic rate, this would make it
> pro-aging due to increased mitochondrial superoxide production. But a
> new paper (2) indicates that CLA increases beta-oxidation in adipose,
> but not muscular, tissue. And the stuff has been repeatedly reported to
> cause weight loss. Questions:
> 
> (1) Does the fact that b-oxidation is increased PROVE a higher metabolic
> rate in terms of OXPHOS in fat tissue (presuming the cell is aerobic),

No, but see (2).

> or might the aldehydes be metabolized by some other mechanism, or be
> exported from the cell?  Or might it just indicate a shift to fatty acid
> from carb as the principal fuel source? Do adipocytes normally burn carb
> to any significant degree? (1) mentions a change in nighttime fuel mix,
> but the abstract gives no details...

See (4).

> (2) IF (2) demonstrates a higher metabolic rate in adipose tissues, is
> it reasonable to assume that the higher metabolic rate reported in (1)
> is entirely due to this? And if so,

I haven't seen the actual numbers, but I would say it's the simplest
explanation.

> (3) Since MiFR says that the preferrential amplification of anaerobic
> mitochondria at the heart of aging is only an issue in postreplicative
> cells (since replicating cells will constantly dilute anaerobic
> mitochondria out), how seriously should we take this theoretical concern
> from an anti-aging POV?

Not very, except that MiFRA might be wrong...  But more to the point, the
studies you cite are rather short-term and study the situation when the
fat content of the animals is falling.  Clearly it will eventually level
off, at which time the effects discussed will presumably diminish.

> (4) Also, (1) reported that CLA reduced nighttime respiratory quotient,
> so that less CO2 was exhaled per O2 inhaled. Does this indicate less TCA
> activity? How does this fit into the picture?

No, what the ratio of CO2 to O2 gives (very roughly) is the ratio of
carbohydrate metabolism and fatty acid metabolism (see your question
(1)), and the TCA cycle is involved in both.  Carbohydrate metabolism
makes about the same amount of CO2 as it uses O2.  Fatty acid metabolism
makes only about two thirds as much CO2 as it uses O2.

> (5) Also, there are several reports that CLA increases lipid
> peroxidation, including this recent one in humans (3), but I can't find
> papers where they compared the peroxidation increases from feeding two
> different groups euqal amounts of CLA and LA. Anyone know anything on
> this point?

No idea.

> (1) Am J Physiol 1998 Sep;275(3 Pt 2):R667-72
...
> (2) Lipids 2000 Jan;35(1):91-8
...
> (3) FEBS Lett 2000 Feb 18;468(1):33-6

Aubrey de Grey





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