Re: mitochondria and aging

From: Robert J. Bradbury (bradbury@www.aeiveos.com)
Date: Sat Oct 23 1999 - 07:21:00 MDT


On Fri, 22 Oct 1999, Zeb Haradon wrote:

> NEW YORK, Oct 21 (Reuters Health) -- Mutations in the DNA found in
> mitochondria -- the tiny ``powerhouses'' that generate energy in cells --
> accumulate over time and may contribute to the aging process, report
> researchers.
[snip]
> In an accompanying editorial, Elizabeth Pennisi says the findings provide
> ``the first hard evidence that mitochondria do deteriorate as people age.''
> Just how this deterioration affects the functioning or survival of cells
> remains to be determined, she adds.
> SOURCE: Science 1999;286:664, 774-779. >>

Well, its been becoming clear for quite some time. One of the original
papers suggesting moving the mitochondrial genome into the nucleus was:
  Med. Hypotheses Aug 1993[!]:41(2):131-3

PubMed Ref:
  http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8231991&dopt=Abstract

This would only have been suggested if there was reasonable evidence at that
time that the mitochondria were involved in aging. Since the paper was 6
years ago, it sounds like [Dr.?] Pennisi is unaware of the literature.

IMO the order of things that need to be corrected to prevent/reverse
aging are:
  a) Telomere Loss
  b) Mitochondrial DNA damage
  c) Protein glycosylation
  d) Accumulation of non-digestable CaRbohydrAte/Protein/lipids [CRAP]
  d) Ribosomal DNA loss through recombination repair
  e) DNA damage causing the accumulation of mutations

This list will get you the major causes of what we call aging.

>
> Something the author of this article fails to postulate about, is that this
> explains why women reach a point in their lives when they are no longer
> fertile, while men continue to be fertile until death. [snip]

This makes a certain amount of sense, since apoptosis is managed
through the mitochndria and the recent report that Bax -/- mice
remain fertile (Bax is involved in apoptosis). It isn't clear
though that you want females to remain fertile indefinately due
to the accumulation of mutations in the DNA in the eggs. It
isn't worth the investment in producing offspring if they are
going to be horribly mutated. Since sperm on the other hand
have to race to the finish line, you can probably argue that
the horribly mutated ones aren't going to make the cut.
What you need is a very effective selection process to cull
out the eggs that have accumulated deleterious mutations.

Robert



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