some questions from Aubrey's book

Michael Sherman sherm at symdyn.com
Wed Jan 12 02:48:56 EST 2000


Aubrey --

I have read your new MiFRA book and found it fascinating,
at least to what little degree I could grasp its contents.
I expect to have to read it a few more times.

I am grateful that someone has finally written a book
that takes a stab at explaining aging.  I eagerly read Steve
Austad's "Why We Age" a while back and was very surprised
and disappointed when I reached the last page and
still had no idea!

Anyway, I have a few specific questions I am hoping
you might be willing to answer for me.


Question 1

In section 6.5.3.1 (pg 71) you discuss the finding
that long-lived species use less (oxidation susceptible)
unsaturated fats in their mitochondrial membranes.
"This is thus very suggestive of the importance of
oxidative stress in aging ..."

But if I understand MiFRA correctly, oxidative damage
to mitochondrial membranes seems relatively harmless.
Mitochondria damaged in that way should be preferentially
mopped up by the lysosomes.  Only damage to mitochondrial
DNA can produce the anaerobic mitochondria which can
accumulate in the cell.  One might even postulate an
anti-aging effect for an easily-oxidized membrane:
its ability to absorb LECs might keep them away from
the mitochondrial DNA and signal lysosome cleanup.

So my question is: do you think the preferential use of
saturated fats in mitochondrial membranes slows the
aging rate, and if so why?


Question 2

Section 6.5.4 on calorie restriction left me unclear as
to whether MiFRA suffices to explain the slowdown in
aging rate produced by CR. As you pointed out, the cellular
metabolic rate is apparently not reduced in calorie
restricted animals.  Does that mean that each
mitochondrion is respiring at the same rate in a CR
animal as in a normally-fed one?  If so, wouldn't they
be expected to fumble electrons and damage their DNA at
the same rate?

Are there any satisfactory, detailed hypotheses explaining
CR in the MiFRA framework?


Thanks and regards,
sherm









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