From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Thu Jul 25 2002 - 04:25:11 MDT
On Wed, 24 Jul 2002, Rafal Smigrodzki wrote:
> ### Remember your mitos!!!
>
> 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 thing is this. If I'm correct about the accumulation of
misrepaired DSB with age, then you are going to get an increased
production of proteins that will not fold properly. The cell's
stress response will go up and activate the pathways to break
down the misfolded proteins. That will lead to a vicious cycle
of producing proteins that will not fold properly and breaking
them back down. That requires a *lot* of energy, increasing the
demand for mitochondrial activity. That will produce more free
radicals that damage the mtDNA as well as the nuclear DNA.
Too much damage to the nuclear DNA (> ~2-3 DSB in humans)
and the cell is likely to commit apoptosis.
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.
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.
You may not find much, but having the mtDNA sequences
at least lets us say "The longevity of these species is
not in the mtDNA, we have to sequence the entire genome."
A longer term project would be to study in depth whether
the other long lived species have evolved better DNA repair
for the mtDNA.
I suspect the Vancouver Aquarium should have fresh samples
of blood from the killer whale recently transported from
Washington to Canada. Perhaps worth a phone call or two
if the mtDNA for killer whales isn't currently known.
Robert
This archive was generated by hypermail 2.1.5 : Sat Nov 02 2002 - 09:15:39 MST