From: Rafal Smigrodzki (rms2g@virginia.edu)
Date: Thu Jul 25 2002 - 13:23:04 MDT
Robert J. Bradbury wrote:
!!
>
> The accumulation of mtDNA mutations is so far the best explanation for
most
> aspects of aging.
I wouldn't be comfortable with "most", I'd agree with "many".
### The way I see it, the main problem due to other causes (nuclear genome)
is carcinogenesis. I would guess that DSB's should not cripple tissues where
cells are replaced, simply because cells with too many breaks will be
replaced from healthy stem cells. It takes a lot more time for the stem
cells to accumulate DSB's, because they are cycling very slowly and have
good repair mechanisms. But I agree that eventually, without the cleansing
that goes on during oogenesis and early embryonic life, even the stem cells
will be sick. I just think it would happen much later than the usual time
for human aging.
Mitochondria are cycling their DNA orders of magnitude faster than the
nuclear genome does, so they are more likely to account for aging at the
tender age of 70 years. Such is my guess - we'll know the answer in the next
10 - 20 years.
-------
The mtDNA theory I think needs to be tuned to account for what
happens if an increasing fraction of the mitochondrial energy
output gets spent in non-productive activities.
### There is less energy left for productive activities, muscle strength
per gram of tissue goes down, cells start accumulating lipofusceine and
tangles, and aging sets in.
-------
Rafal, you should have as a side project sequencing the
mitochondrial genomes from species who seem to have
evolved alternate paths to longevity to see if anything
interesting shows up. On my list: Elephants, parrots
(& other long-lived birds), bats, and any whales, esp.
bowhead whales that are reputed to live several hundred
years.
### I see your point but I'm sure I can't convince my boss that killer
whales have anything to do with Parkinson's disease.
Rafal
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