Yet More to Blame on Damaged Mitochondrial DNA

The more age-related disease and damage can be sourced to the ongoing accumulation in our cells of faulty mitochondria with damaged mitochondrial DNA, the better. We already know about the acceleration of free radical production central to the mitochondrial free radical theory of aging. In addition, we've seen suggestions that the advancing rate of nuclear DNA damage with age could have something to do with mitochondrial damage, as well as a potential link between telomere shortening and mitochondrial damage:

The discovery of more benefits from repairing mitochondria mean a greater likelihood of significant funding for medical technologies capable of achieving that end. The present state of science when it comes to wholesale replacement of damaged mitochondria or mitochondrial DNA is very promising, with the important exception of the money side of the research equation. It has been several years since protofection of new mitochondrial DNA was demonstrated to work in mice, and other groups have shown similar results since then via mechanisms discovered in tropical parasites, but the state of funding in no way matches the potential for this sort of research.

In short, we're all set with a brace of breakthroughs, but need a big flood of funding to support the development of these mitochondrial repair and replacement techniques in humans. From there, widespread application to reverse the damage of aging can hopefully follow. It seems likely, given the state of health of the average 30 year old, that a mitochondrial overhaul is something needed once every few decades at most - it takes a while for the damage to rise to the level that causes age-related disease.

If you head on over to ScienceNOW today, you'll find another good reason to fully develop mitochondrial repair and replacement technologies:

Cancer often strikes its final, fatal blow when a tumor spreads to other organs. A new study published online today in Science sheds light on this poorly understood process, called metastasis. The researchers report that mutations in mitochondrial DNA [mtDNA] can spur metastasis and that it can be reversed with drugs, at least in mice.

The precise mechanism isn't yet pinned down with certainty, although excess free radical production looks plausible, but the evidence pointing to damaged mitochondrial DNA as enablers of metstasis is pretty convincing. I hardly need to point out that the cancer research community is more or a less a flood of money in motion; if some of that weight of funding is directed to the repair of mitochondrial DNA, the resulting technologies will lead to far broader benefits.


Hmm, while we wait for the technology for mitochondrial repair to be developed, perhaps we can do something to help our mitochondria create less ROS? (sounds silly I know, but e.g. paper "The ketogenic diet increases mitochondrial uncoupling protein levels and activity", or paper "Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation", there are other papers that explain pathways in detail).
Calorie restriction seems to positively affect mitochondria, but what if we use calorie restriction based on ketone bodies as the main energy source (instead of calorie restriction based on carbohydrate as the main energy source)? If mitochondria are the "powerplants", maybe it is important what kind of "fuel" they use - perhaps, there exists a fuel that creates less "pollution" (ROS)?

No, I do not advocate for any popular or widely-known "ketogenic" diets (I do not follow any of those because they seem very unhealthy for the most part).

Posted by: Sense at April 9th, 2008 11:26 AM

That sounds very promising. Are there any companies doing research in this specific area? Alternatively, is there any way that I can donate money which specifically targets research in repairing/replacing mitochondrial DNA?

Posted by: Jim Thomason at April 11th, 2008 10:52 AM

The Methuselah Foundation, as I'm sure you're aware, works on the alternative approach to replacing or repairing the DNA: moving the vital portions to the nucleus. They accept donations of any size.

I don't know of any funded companies working on mitochondrial DNA replacement at this time, or ways to donate modest amounts to those research groups that are working on the science. You might consider contacting researcher Rafal Smigrodzki, who was a part of the protofection efforts, and may know more:

Posted by: Reason at April 11th, 2008 11:14 AM
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