h a l f b a k e r y
Clearly this is a metaphor for something.
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Aging is complex and poorly understood,
but at least one component of it is
probably the degeneration of
mitochondria - the little diesel engines of
your cells. Mitochondria have their own
DNA, and over the years this becomes
damaged (more rapidly than the DNA in
the cell's nucleus, because
of all the
oxidative reactions that happen in
mitochondria) and the mitochondria
become moribund. Your cells lose their
Now, mitochondria are basically
bacteria. And bacteria can be infected by
their own type of virus, called 'phage.
'Phage work by injecting their DNA into
the bacterium. Ergo, it should be
to design a modified 'phage that would
put new DNA into your old mitochondria
a sort of mitochondrial genome upgrade.
So, regain the energy of your youth!
(Parallel research programme: beat
Alzheimer's, so you can remember what
do with all that youthful energy).
Mitochondria and aging
Overview of potential role of mt's in aging. [Basepair, Mar 11 2005]
||Mitochondrial gnome refurbishment......
||<annoyingsnigger> Sne sne sne</annoyingsnigger>
||I like the idea that bacteriophages might recognize mitochondria, and that they could thus be genetically engineered. + for that alone. The idea that cells age because of mitochondrial wear is also interesting, and plausible. Do you have a link?
||This is a bad idea, because....
||1) There's no way of getting a phage into the mitochondria. You'd have to get it into the (Eukaryotic) host cell first and phages don't do that. Even if they did work on Eukaryotic cells, the viral DNA would have to penetrate the walls of the Mitochondria after penetrating the host's, and since it loses the protein coat as it enters the cell....
||2) Mitochondria can't be all that important to the aging process because they don't get "younger" when we reproduce. Unlike cells, which undergo mitosis and recombination as part of the reproductive act, mitochondria just get handed down from the mother to the child. (If you're a guy, your mtDNA is screwed, evolutionarily speaking.) Fetal DNA is as "old" as the mother's DNA as far as its genes go. Hell, that means ALL mtDNA is REALLY, REALLY old.
||There's no such thing as a bad idea.
||Madcat - I'd thought of the problem of
getting a virus that'll get into both
eukaryotic and prokaryotic-like cells.
What we need is a Trojan Horse virus.
basically, you make a phage genome
but you package it in vitro with
eukaryotic viral coat proteins. This
infects the eukaryotic cell. The phage
genome encodes the packaging
proteins necessary to re-package it as
an active phage to enter the
mitochondria. With a nifty bit of
coding, you could (hopefully) ensure
that the phage-coat-encoding genes
were inactive in the mitochondrion (by
suitable choice of promotors perhaps).
The phage would also encode, of
course, a fully active mitochondrion.
||As for the relevance of Mt's to aging,
there is a lot of evidence to suggest that
they are at least one of the factors. I
honestly don't know why maternally-
inherited mt's don't degrade over the
generations, but presumably they are
reproductively priviledged in the same
way as the oocyte and sperm genomes
are (since, by the same token, the
genomes of reproductive cells are as
old as the species)? . In any case, it is
well documented that old mitochondria
(I mean, those from an old person) have
a higer level of DNA damage than those
from a younger person.
||I'll find a link on the mitochondrial
business for you and Bungston...
||An example link re Mt aging has been
added, but run a Google search and
you'll find others. If you have access to
the journals I can dig out some
references (probably from Cell). There's
also some work whereby they made
transgenic mice with a defective
mtDNA-repair enzyme; these mice
accumulated mtDNA damage faster
than normal mice and also aged faster.
Of course, this is not equal to saying
that better mitochondrial maintenance
extends lifespan, but it is suggestive.
||/Hell, that means ALL mtDNA is REALLY, REALLY old/. Think about that. Your entire current bodily supply of mitochondria was not packed into the egg that became you. Yes, you got mitos from your ma. But you make new ones as you grow.
||[Bungston] - there are two questions
getting confused here, I think.
Certainly your mitochondria reproduce
along with your cells, so their DNA is
not "old" in that sense. But Madcat's
point (I think) was that there is a direct
descent of mitochondrial DNA through
the generations, and therefore it (I
mean, its sequence) cannot be
degrading (mutating) significantly over
||HOWever - my response to Madcat's
point was that there is clearly a
mechanism which protects (or screens
out bad) mitochondrial DNA in the germ
cells. So, the fertilized egg contains
well-nigh perfect mitochondria. But the
mitochondrial DNA in somatic cells
mutations and base modifications
during the lifetime of an individual, and
it's *this* damage which you might try
to correct by mt genome replacement.
||As with all aspects of aging, no-one
really knows what the underlying
mechanism is (and there are probably
many), but accumulated mtDNA
damage is one of a few very strong
||Just hope it doesn't mutate and kill all your mitrocondria. That would become the new definition of 'bad'.
||What an interesting thread. I wonder why there are not cancers of the mitochondria? Every other cell in the body can become malignant. Mitochondria must have some mechansims by which they determine that there is a need for them to reproduce. Why doesn't this go haywire sometimes such that the cell winds up packed with mitos?
||I guess because such a cell would then die, and that is that.
||I think mitos must have a mechanism for correcting DNA damage. Many such mechanisms exist in cells. I think mitos have their own DNA polymerase. Hmmm - in over my head here.
||I think the argument that the phage would need to penetrate the cell is a pretty good one. The cell doesn't like stuff like that. Probably part of why the mitos moved in in the first place.
||[Jesus H Christ] When my uncle was a
kid he tried to immitate a cartoon-
character superhereo who would throw
around burning stones. He poured
lighter fluid on a rock, held it in his
hand, and then lit it. That was
definitely a Bad Idea.
||"Just hope it doesn't mutate and kill all
your mitrocondria. That would become
the new definition of 'bad'" [my-nep]. It
certainly would. And it would sort of
counteract the longevity benefits.
||" I wonder why there are not cancers of
the mitochondria?" [Bungston] That is a
bloody good question! I guess (as you
did) that it would be a self-limiting
disease, confined to a single "host" -
i.e. one cell. But maybe there are some
diseases where mitochondrial numbers
are not regulated....will have to look.
||Would it be possible to use increased
mitochondria to ramp up the human
metabolism? If it were possible, would
that then cause a concomitant rise in
the onset of aging, due to the increased
number of toxins, free radicals and
metabolic byproducts resulting
from increased food intake?
||Mitochondria have been linked to
intelligence; could they make us a smart
race of super-strong, really twitchy
insomniacs (due to high metabolism)?
||This kind of tinkering would need an
extraordinary amount of testing before
being used on humans.
||Still, I would love this technology to
exist. Faster, please!
||I don't think tinkering with the normal
levels or activities of Mts would be a
good idea - they'll've evolved to
something close to an optimum in a
young body. But aging is non-evolved
- evolution doesn't really give a toss
once you've stopped reproducing. So,
there's probably plenty of room to
improve on what happens to us once we
pass forty or so.
||I didn't know that Mts had been linked
to intelligence, except that their
degeneration in brain cells may be one
of the factors that adds to its general
degeneration with age. But increasing
their basal level of activity sounds like a
||"This kind of tinkering would need an
extraordinary amount of testing before
being used on humans." [justibone]
Yep, it certainly would. On the other
hand, I think that it's generally more
persuasive to test novel disease
therapies on people who have the
disease in its terminal form. In the case
of aging, that's pretty much everyone