How Age-Damaged Mitochondria Cause Your Cells To Age-Damage You
Free radicals, and reactive oxygen species (ROS) in particular, play an important part in aging. These are (usually small) molecules lacking an electron needed for stability; they will steal an electron from the first thing they bump into. Like pulling a cog out from clockwork, stealing an electron from a protein or enzyme is usually not good for the finely-tuned biochemical machinery of our cells. The free radical might be rendered safe in the process, but it has left some form of chaos and damage in its wake.
Free radicals are sufficiently dangerous to biochemical machinery that some of our body's defenders use bursts of free radicals as a kill mechanism.
Scientists generally concur that accumulated damage throughout the body due to free radicals is one important root cause of age-related degeneration - but the devil is in the details. The vast, overwhelming majority of those free radicals are generated by your own metabolism as an unavoidable byproduct. The rate of free radical generation increases greatly with age as the basic mechanisms of your of metabolism are themselves damaged by the free radicals they created. This is not a one-step process, however. I'll try to walk through it at a high level, cribbing from the mitochondrial free radical theory of aging that was proposed by Aubrey de Grey and working its way into general acceptance.
- Within each of your cells are many mitochondria, tiny biochemical power plants that convert chemicals from food to ATP, the basic fuel molecule used by your cells to provide energy for life.
- Mitochondria were once a separate organism that came to live in symbiosis with ancestral cells. As such, they brought their own DNA to the party; some of it still remains within our mitochondria, separate from the DNA we carry in chromosomes in the cell nucleus.
- Mitochondria have a couple of ways of generating ATP. The more efficient of these methods - oxidative phosphorylation (OXPHOS) - generates some amount of free radicals as a natural byproduct, and requires the proteins coded in the mitochondrial DNA to function. It is the predominant way by which healthy cells generate their power.
- Free radicals created through OXPHOS within a mitochondrion are most likely to damage that mitochondrion; they're very reactive, so they won't get far before sabotaging something. The components that really matter are (a) a membrane that helps organize the movement of various chemicals in the process of generating ATP, and (b) the mitochondrial DNA.
- Sufficient free radical damage to mitochondrial DNA shuts down OXPHOS within that mitochondrion, as the necessary proteins can no longer be produced. The mitochondrion switches over to using a less efficient method of producing power, one that doesn't produce free radicals, but has to run at a much higher rate to produce the same level of ATP.
- Mitochondria, like most cellular components, are recycled on a regular basis. Components called lysosomes are directed around the cell in response to various signals, engulfing and breaking down damaged or worn components. After the herd has been culled, surviving mitochondria within a cell divide and replicate, much like bacteria, to make up the numbers.
- The signal to break down a mitochondrion is triggered by sufficient damage to its membrane: a sign that it's old, leaky, inefficient and needs to be replaced with a shiny new power plant.
- BUT: if a mitochondrion has had its DNA damaged to the point of stopping OXPHOS, it will no longer be producing free radicals that can damage its membrane. So it will never get broken down by a lysosome. When the time comes to divide and replicate, it will replicate its damaged DNA into new mitochondria. None of those new mitochondria will be producing free radicals via OXPHOS, and so will not be recycled either.
- One DNA-damaged, non-OXPHOS mitochondrion will eventually take over the entire mitochondrial population of a cell in this way. At that point, the trouble really gets started.
- By the time you hit late life, perhaps 1% of your cells are in this state of being taken over by non-OXPHOS mitochondria. As for any neighborhood or city, it only takes a small proportion of dangerous criminals to make life really unpleasant for the rest of us.
- Non-OXPHOS mitochondria have the unfortunate effect of depleting a needed molecule used in many cellular processes, NAD+. This is a carrier molecule in the OXPHOS process, given an electron (and turned into NADH in the process) to port between point A and point B within the mitochondria. Once the electron is delivered, the NADH becomes NAD+ again. But without a working OXPHOS process to return NAD+ into circulation, the cell would quickly build up a deadly excess of NADH, run out of NAD+ and die.
- Fortunately for the cell, and unfortunately for us, there is another way to recycle NADH into NAD+. Since NADH is just NAD+ with [amongst other things] an electron stuck to it, all the cell has to do is export those unwanted electrons.
Editing for clarity on 11/22/2009: In the bullet points above, I omitted details of the reaction that transforms NAD+ to NADH in order to focus on the electron that is ported around. Wikipedia gives an introduction to the full picture, which also involves an extra hydrogen atom - NADH is NAD+ with the addition of a hydrogen atom (one proton, one electron), and an additional electron. Nonetheless, it is the shuttling and exchange of electrons that is important here.
- In a form of chemical waste dumping, this is just what the cell does. Structures on the cell membrane known as the plasma membrane redox system (PMRS) export electrons from NADH, recycling it into NAD+. This process is only very active in cells which have been taken over by DNA-damaged, non-OXPHOS mitochondria, but their outer surfaces are little hotspots of electron dumping.
What do these electrons do? Well, for one, they combine with oxygen molecules - which are abundant in any of our living tissue - to create reactive oxygen species (ROS): more free radicals. So you have the Rube Goldberg system outlined above whereby a few free radicals have caused a cell to become an ongoing, major exporter of free radicals into the surrounding environment. These will make life unpleasant for surrounding cells, but that is most likely not the real problem. ROS just can't travel far enough to explain how a corrupt 1% of our cells can cause a large fraction of the difference between being young and being old.
A more likely target for all the newly created ROS is cholesterol. Cholesterols, such as low-density lipoproteins (LDL) are used everywhere in the body and travel widely. If ROS reacts with nearby LDL - and there will always be nearby LDL - to form damaged, oxidized cholesterol, that damaged cholesterol can then be incorporated into and further damage biochemical processes throughout the body. For example, its effects on our arteries is well known:
In conditions with elevated concentrations of oxidized LDL particles, especially small LDL particles, cholesterol promotes atheroma formation in the walls of arteries, a condition known as atherosclerosis, which is the principal cause of coronary heart disease and other forms of cardiovascular disease.
There are many other ways in which accumulations of oxized cholesterol can send biochemical processes awry. This, then, seems to be a good candidate for the plausible, systematic method by which a small number of cells can work such varied damage upon your entire body.
Aubrey de Grey has proposed an engineering solution to this problem, based upon this way of looking at it. That is to go straight to the root, and get the OXPHOS process working again by (a) moving mitochondrial DNA into the nucleus, and (b) ensuring that the necessary proteins can make it from the nucleus back into the mitochondria where they are needed.
As usual, we're lucky - evolution has done the hardest part of this for us already. Mitochondria are very complex -- there are about 1000 different proteins in them, each encoded by a different gene. But nearly all of those genes are not in the mitochondrion's DNA at all! -- they are in the nucleus. The proteins are constructed in the cell, outside the mitochondrion, just like all non-mitochondrial proteins. Then, a complicated apparatus called the TIM/TOM complex (no kidding...) hauls the proteins into the mitochondrion, through the membranes that make its surface. Only 13 of the mitochondrion's component proteins are encoded by its own DNA.This gives us a wonderful opportunity: rather than fixing mitochondrial mutations, we can obviate them. We can make copies of those 13 genes, modified in fairly obvious ways so that the TIM/TOM machinery will work on them, and put these copies into the chromosomes in the nucleus. Then, if and when the mitochondrial DNA gets mutated so that one or more of the 13 proteins are no longer being synthesised inside the mitochondria, it won't matter -- the mitochondria will be getting the same proteins from outside. Since genes in our chromosomes are very, very much better protected from mutations than the mitochondrial DNA is, we can rely on the chromosomal copies carrying on working in very nearly all our cells for much longer than a currently normal lifetime.
A great deal of work is needed to make this happen, even with today's biotechnology. But if you don't get started, you'll certainly never finish! Generous donations to the Methuselah Foundation help to fund the first steps in this direction.
Technorati tags: aging, biotechnology, medical research, SENS
Why don't you hire a PR/marketing agency that will do the publicity for normal people who are in the "pro-aging trance". If done right, it would get 1000x more funds in no time.
Not to discount Aubrey de Grey's contribution, it was Denham Harman who first proposed the mitochoncrial theory of aging in 1972. Harman was the father of the free radical theory. The mouse work has already been done by Bruce Ames at the Univ of California Berkeley and mitochondrial antioxidants carnitine and lipoic acid were shown to "youthify" old rodents. The bragging right for the first anti-aging pill (carnitine+lipoic) go to Dr. Ames, who patented the combo and later made the front cover of Reader's Digest.
In regard to the mitochondria, this is where most of the oxidation is generated in living tissue and most of that oxidation is generated by iron-induced free radicals. Lipofuscin (aging pigment) accumulates which results in defective mitochondria. Iron chelators such as inositol hexaphosphate (obtained from bran) serve to detoxify the mitochondria from iron-induced damage.
DeGrey's text only furthers the focus on mitochondria and aging, and is worthy reading for the astute follower of anti-aging theories.
Bill Sardi
Yes; I wasn't intending to imply that the earliest mitochondrial free radical theory originated with de Grey. His contribution was a synthesis of experimental observations and results at the time into a modified theory that could explain them all. The prevailing alternate view was that progressive damage to the mitochondria made them produce ever more free radicals in a feedback loop or death spiral; observations in the field clearly contradict that theory.
This article is very informative, but it still raises an amount of questions.
1% of non-oxphos in mitochondria simply doesn't seem sizable. As you say, the damage is split between the electrons sent out damaging parts in the cell, or cholesterol... but how much would that be, really? 1% of mitochondria? Wouldn't you need a lot more?
Perhaps I'm underestimating the rate at which they are produced by the 1%, but I still picture most of the cholesterol-damaging free radicals to come from the external environment, bacteria, etc. That so much could somehow escape the mitochondria and seek out cholesterol isn't very easy to picture.
If 1% makes such dramatic changes to humans over time, then would 2%, 3%, 5%, shorten our lifespans to a mere year or two? Perhaps we could do testing for the amount of non-OXPHOS byproducts found in people of various ages to figure this out.
Tyciol: it's not a case of free radicals escaping the mitochondria in that 1% of cells. It's that those cells have shifted into a state whereby they are generating a vastly greater amount of free radicals at their outer surface than the mitochondria ever did internally.
The root cause of that shift in state is the damage of mitochondria by free radicals, but the end result is a different engine for generating of free radicals - with a larger output and more capable of spreading the damage throughout the body.
Such is the theory, in any case.
So the main bad thing about this is that the membrane is supposed to be damaged before the DNA is damaged enough to shut down OXPHOS. I'm betting mitochondrial DNA has some backups to prevent this from happening, and that free radicals would be oriented towards the membrane rather than DNA, otherwise the DNA should be damaged very early in its lifespan.
Even so, somehow it happens anyway, but why? What are the odds?
One possible reason for this delay I just now theorized is... perhaps there is a limit to the onset of these mitochondrial DNA. I'm not certain they would be able to take over an entire cell.
Inside a cell, if the free-radical-expelling non-OXPHOS mitochondria continue to replicate, this means that that cell will have more and more free radicals. What is in close proximity to a mitochondrion? Other mitochondria! By damaging the cellular membranes of other mitochondria, they are going to be pushed towards death.
At first I thought "this would just be indiscriminate, and kill an equal amount of OXPHOS and non-OXPHOS mitochondria, so it wouldn't upset the ratio, but then I realized: it would!
The DNA of a normal mitochondrion won't be as damaged as a non-OXPHOS. They are constantly dying off and being replaced, which perhaps means the ones with the most damage die faster and the least damaged mitochondrion is naturally selected to fulfill the role of duplication.
This doesn't stop the takeover of a non-OXPHOS, but it points out the idea that they will have accumulated DNA damage prior to OXPHOS shutting down. In addition to shutting down OXPHOS, the OXPHOS-produced internal free radicals must have also indiscriminately damaged many other parts of the mitochondrial DNA, and probably the mitochondrial membrane as well, as compared to normal mitochondria which are constantly dividing and refreshing their membranes.
This weaker membrane in the non-OXPHOS means that less free radicals would be needed to rupture it. This would slightly skew favour in the OXPHOS geneline surviving, and the non-OXPHOS geneline being selected against.
This wouldn't likely totally eliminate them, but simply slow them down a bit. Even if it didn't, as non-OXPHOS approached the majority level of mitochondria in a cell, they would have to die off a lot. Also, during mitochondrial division there would have to be replication errors which eventually messed them up too much to properly replicate.
Of course, this wouldn't really negate the theory: only a small amount of non-OXPHOS are needed to cause problems, and this defence mechanism I thought up wouldn't kick in until there were way too many, as in, you're already dead by that time :p Still, who knows, might come in handy later.
I'm not sure I entirely understand your proposal, but the main point in my original proposal back in 1997 is that damage to the mitochondrial DNA correlates inversely with damage to the mitochondrial membranes. A mitochondrion whose DNA is damaged will normally fail to assemble a respiratory chain, so it won't make as much free radicals, so it will damage its membrane more slowly than a non-mutant mitochondrion does. I proposed that the damage to the membrane is what drives mitochondrial destruction (autophagy); thus, mutant mitochondria stay out of trouble and proliferate by default.
Yeah... I think I got confused somewhere writing that. What I meant was, the relationship of non-OXPHOS with DNA damage. Once they switch over they'll have less free radicals so damage to both DNA and the membrane would be slower. But since for some reason damage has been more focused towards DNA than the membrane, maybe that means other parts of the DNA have been damaged more compared to the OXPHOS which are continually dying off and renewing themselves, naturally selecting those who have not accumulated damaged DNA.
So what I was wondering is, the nonOXPHOS, perhaps since they have accumulated more total DNA damage, maybe the ones required for mitochondrial mitosis are also damaged, and then they'll still be around but maybe still replicate more slowly on average than the average OXPHOS mitochondrion.
Anyway, I barely know what I'm talking about, so I'm going to change the subject. I was reading Ray Kurzweil's news and game across this: http://www.the-scientist.com/article/home/36660/
Apparently these are these bacteria that infect a mitochondrion and eat it from the inside, killing it offslowly. They said it might just happen to damaged or old mitochondria. Do you think there'd be some way to target nonOXPHOS ones with these? Like a way of waste disposal.
I mention the mitophages here:
https://www.fightaging.org/archives/001082.php
In terms of affecting mitochondrial function, here's another interesting parasite and mechanism:
http://www.longevitymeme.org/news/view_news_item.cfm?news_id=2736
There are a few fundamental problems with this hypothesis of mitochondrial degradation. Generation of superoxide by mitochondria is part of a neccessary regulatory pathway, particularly in neurons.
Let us consider a motor neuron and how mitochondria number is regulated. Motor neurons can be large, a meter from the cell body in the spine to the tippy end of the axon at the muscle. All the mitochondria in that motor neuron are made in the cell body and transported out to the tippy end. When the get "tired", they are transported back for disposal at the cell body by autophagy and recycling of metals and perhaps other stuff. How does the cell regulate the number of mitochondria? When the motor neuron is small, so is the number of mitochondria. As the motor neuron extends, the number has to increase by 3 orders of magnitude. The only way mitochondria number can be regulated is via feedback control (open loop control simply isn't precise enough).
For that control to occur, there must be a signal that is proportional to the metabolic load that each individual mitochondria experiences over its lifetime (about 30 days in the CNS in rats). I have suggested that the signal is nitrotyrosine produced in response to superoxide generated in response to elevated mitochondria potential. Integrated over the mitochondria lifetime, that signal is proportional to the metabolic load experienced.
When the mitochondria is recycled during autophagy, the nitrotyrosine is converted to a nitrosatively active species, either an RSNO, nitrite, or NO, and that NO then initiates and regulates mitochondria biogenesis.
In mitochondria, superoxide is vectorally produced into the inner matrix, it is not exported. In the inner matrix, there is MnSOD, which destroys superoxide at near diffusion limited kinetics. Much faster than superoxide damages DNA.
In neurons, new mitochondria are made in the cell body, migrate out to the tippy end by being moved along by ATP powered motors along the outside of the axon. When the mitochondria potential falls, the mitochondria is moved to the center of the axon and moved back to the cell body for recycling. The mitochondria can persist for significant periods of time with damaged DNA. They cannot replace damaged mitochoondrial proteins, but for the most part, they are pretty resistant to oxidative damage (particularly cytochrome c oxidase which is very oxidative damage resistant, much more so than is DNA).
I have started blogging about nitric oxide. It is nitric oxide that sets the ATP setpoint and which regulates cell repair by invoking the "rest and relaxation" response. For the most part, most damage occurs during the "fight or flight" state when cells divert ATP from repair to current consumption such as "running from a bear". Inappropriate activation of the "fight or flight" ATP conservation pathways is what causes essentially all degenerative diseases (in my opinion). A start on that is in this blog on the placebo effect.
http://daedalus2u.blogspot.com/2007/04/placebo-and-nocebo-effects.html
Dear Reason:
Could you please point out the original article about
"The mitochondrion switches over to using a less efficient method of producing power, one that doesn't produce free radicals, but has to run at a much higher rate to produce the same level of ATP". you Posted by Reason at October 8, 2006 1:30 PM.
Thanks
Hey... I love your idea...
I’d like to see more research on this... Have you tested the cells of old mouse with caloric-restriction diets to verify that it is mitochondrial degeneration only that is killing them?
I think that it might be possible, that in cells with efficient autophagy, mitochondrial recycle mechanism is working correctly and aging is based on other factors
Swiss scientist at ETH have developed a GTE that will up-regulate mSOD by 650% and is up to 1200 times more powerful than the GTE used in research. This would be the most powerful anti-aging (free radical scavenger) available today. Dr. Hans Holsgang, et al spent the past 10 years and over 10 million dollars to achieve this.
In light of what you say about the damage done by free radicals produced by the mitochondria and the idea you propose of alleviating this by targeting antioxidants into the mitochondria, would say say that the antioxidants that we get from our food are worthless? After all, there are a number of studies suggesting that fruit and vegetables have an important role in opposing several serious illnesses such as cancer. I'm thinking especially about the kind of antioxidants that occur in the much touted blueberries and broccoli, and other various kinds of fruit, berries and vegetables. Even if these antioxidants don't reach the mitochondria, they must do some good within the cells or in the environment around the cells.
It is thought that antioxidants from the dit do get into the cell itself but probably not in the mitochondria. It maybe that the free radicals in the cell are reacted with these and protect certain proteins and RNA etc.
The account of OXPHOS presented at the start of this skein is mistaken about key electrochemical features about NAD and H+ (not NAD+). When + is shown, it means an atom or molecule has given up an electron, not the other way around. What is involved in the innermembrane space is not oxidation, but the splitting of NADH into NAD and H+. The electron freed goes into the matrix to form hydrogen peroxide which is either then captured as ATP, or degenerates, giving off heat. Spontaneous ATP turnover or hydrolysis also results in heat. Hydrogen peroxide is the aqueous from of reduced oxygen, always found at the anode of a battery discharging into an electrolytic solution. Oxidation does not take place at the anode. Oxidation is the splitting of NADH, and occurs in the innermembrane space. That means it has an extra electron, and does not need to scavenge one.
It has been noted that the F1 rotor of the ATP synthase complex rotates counterclockwise with ATP hydrolysis, and clockwise with ATP synthesis. Direction of rotation of the rotor is harmonious with the lelf-hand-palm law that describes electrostatic pressure induced by an electron that is moving.
In essence the mitochondrial free radical theory of aging is based upon a mistake, if it is anything like what is described here. This in itself does not refute the theory. It merely denies it has any foundation in a sound model of electrochemistry that envisions redox coupling. Refutation is not called for when the theory's inconsequence for understanding aging and metabolism is the measure of theoretical soundness. So far the theory has resulted in nothing except sales pitches for food supplements. It has not allowed aging or metabolism to be better understood so that either could be influenced by these very food products, unless we were to allow anecdote in the court of science.
Aubrey de Grey, in the Millard Foundation video entitled "Regenerative Medicine: Why and When?" says straightaway that there is still a great deal of ignorance about the nature of metabolism. de Grey's hypothesis does nothing to dispel this ignorance, and, in fact, compounds it by roiling the waters with uninformed accounts of redox activity, and compliance with century old life science traditions that hold thermogenesis is a part of metabolism. It is to be expected that he waves off those who want to do anything about aging by studying metabolism, and directs them to engineering strategies designed to fight an expensive rear guard action that few could afford even if they worked.
@O'Kelly: the error in this post is mine. This wikipedia page is a better resource:
https://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide
If you want to critique de Grey, you should critique his primary material - i.e. the book he wrote that outlines the mitochondrial free radical theory of aging.
Mitochondrial not free-radical theory of aging
http://aiexandr2010.narod.ru/
i do not realy understand theory behind oxidative stress in aging.how does the oxidative stress lead to aging i mean what is the mechanism
the theory of Aubrey de Grey, is not explained how in mammals including us when they reach old age or because of diseases such as Parkinson's, Alzheimer's or diabetes.the mitochondria produce a greater amount of superoxide and hydrogen peroxide if the theory electron transport chain is impaired, so should not cause this increase.
@oscar miño: the damaged mitochondria produced via clonal replication in the process outlined in the post only take over a fraction of the number of cells in the body. Say a few percent of the total. That's enough to cause the resultant harm, however.
Mitochondrial theory of development, aging and carcinogenesis was first proposed in 1978 (1), and further discussed by the author in 1985 (2).
There isn’t a word in this theory about free radicals. And until that time there wasn’t other mitochondrial theory of aging.
It is now clear that the free radical theory of aging is not true - in many cases there isn’t even a correlation. On the other hand, increasing evidences suggest that the slowdown in reproduction of mitochondria in highly differentiated cells is the cause of creating of deleted mtDNA and serves as a selective pressure for the selection of deleted mtDNA, which, in the exacerbation of competition with wild-type mtDNA for the missing components for reproduction, have a selective advantage because of shorter length of the molecule, as it was predicted (2).
1. Chemical abstracts. 1979 v. 91 N 25 91:208561v. Role of mitochondrial processes in the development and aging of organism. Aging and cancer. Lobachev A. N. (Inst. Biol. Fiz. Pushchino, USSR). Deposited Doc. 1978, VINITI 2172-78, 48 pp. (Russ). Avail. VINITI. A review with 109 refs
2. "Biogenesis of mitochondria in the differentiation and aging of cells." A.N. Lobachev, Moscow 1985. VINITI 19.09.85, №6756-В85 Dep.(28p.)
http://aiexandr2010.narod.ru/
You state too many things as fact in this article, eg. the endo-symbiotic theory is a theory, admittedly a good one, but it is not fact and should not be stated as fact.
I'm not suggesting I know better, but when reading I found that if everything you say is factual I can hardly beleive all of it.
How close are we to a stem cell cure for Mitochondrial disease? And if there is not a substantial cure, perhaps one could try stem cell therapy say in Arizona at one of the clinics? Or perhaps there might be someone who knows more in another country and would attempt the therapy. The toxicity from a statin drug caused the problem causing much myalgia.
Simon, mitochondrial endosymbiosis has a veritable mountain of evidence behind it. Sure its still a theory, but since its not one you're able seriously challenge, your criticism is the very definition of pointless. It serves only as a reminder of how narrow the concept of 'fact' is in modern science.
As I understand the process the energy cycle is initiated by coenzyme a which also detoxifies and repairs mitochondrial DNA & RNA. Also coenzyme a provides anti-oxidant power to clean up free radicals that are formed by metabolism.
Great information on explaining the science. Where are the action items ?
What does one do or take to deal with these issues. I have a list of fav. anti oxidants.
But i am no pro; would love to see an expert give a TO DO List on applying the science.
Thanks.
ray
@ j r ristorcelli: the action item is to support research into one of the ways to repair or replace mitochondrial DNA:
https://www.fightaging.org/archives/2011/06/many-possibilities-for-mitochondrial-repair.php
The easiest way to do that is to donate to the SENS Research Foundation:
http://sens.org/donate
since !% mtdna mutants v 99% wild type might one therapy consist of a factor that would target all mitochondria for destruction to a low level with resultant replication displacing mutants?
Reason, does this achievement help? http://www.ibecbarcelona.eu/genetic-editing-a-new-tool-to-fight-inherited-disease/
Google David Sinclair / NAD + and also Leonard Guarante - Nicotinamide Riboside supplementation restores NAD+ levels to youthful levels in rodents AND humans - 2015 breaking news
Wow, I am blown away by one thing here, it is the dates and timeline. All of this funding and rhetoric for such a ssssllllllooooooowwwwwww (slow) moving process. There is a lot of talk about the great pace of these technologies - obvious that is not happening or at least not translating into anything that is helping people NOW. Enough talk, take what you know now and bloody well create a treatment with it. NO ONE will ever know if you are right (and brilliant) or just another quack unless you actually accomplish USEFUL and get it to people. I will pay (likely way more than I should) for a treatment that show promise long before I will piss away money on another academic waste of valuable time paper.
@Robin: Gensight is presently funded with tens of millions of dollars and the staff there are developing the first working means to prevent the consequences of mitochondrial damage. Their technology is based on research funded by the SENS Research Foundation, using donations from the community given a couple of years after this 2006 post was written. Here is the write-up:
https://www.fightaging.org/archives/2015/07/gensight-developing-a-mitochondrial-repair-therapy.php
Progress happens. Yes it is slower than you'd like. If you want to speed it up, write some large checks.
Spark Therapeutics announced yesterday that they will be taking a gene therapy treatment for LHON (Leber Hereditary Optic Neuropathy) into clinical trials. I presume that they will be using the same Mitochondrial Targeting Technology that Gensight are using (which was developed in Marisol Corral-Debrinski's lab and partially funded by the SENS Foundation).
http://www.fiercebiotech.com/press-releases/spark-unveils-vision-having-10-clinical-stage-gene-therapy-programs-2018-in
http://www.gensight-biologics.com/index.php?page=mts
How close are we to a stem cell cure for Mitochondrial disease? And if there is not a substantial cure, perhaps one could try stem cell therapy say in Arizona at one of the clinics? Or perhaps there might be someone who knows more in another country and would attempt the therapy. The toxicity from a statin drug caused the problem causing much myalgia.
How outdated is this article? Apparently after reading it, I'm ill informed...
http://www.longecity.org/forum/topic/99678-question-can-scientists-distinguished-damaged-dna-from-healthy/
@Nathan: Can you be more specific?
Anyway, you can find some relevant papers here: http://www.sens.org/research/publications?keys=&research_themes_tid=253&field_publication_type_value%5B%5D=1&field_publication_type_value%5B%5D=2&field_publication_type_value%5B%5D=2a&field_publication_type_value%5B%5D=3&field_publication_type_value%5B%5D=4&field_publication_type_value%5B%5D=5&field_publication_type_value%5B%5D=6&items_per_page=50
Cells that have so many mitochondria misbehaving as to affect other cells around them are simply senescent cells, just as they would be senescent cells if any other mechanism within them were massively misbehaving. The senescent cells profoundly affect other cells around them, which in turn, disrupts the extra-cellular matrix and that, in turn, affects yet more cells, creating a domino effect that leads to aging.
It seems to me that the answer does not lie in dangerously tampering with nuclear DNA by adding mitochondrial genes as proposed here. It is simply to kill off the senescent cells. Once dead, the malfunctioning mitochondria will die too. Then, some time later, the dead cells will be cleared by the body and replaced, via healthy stem cell division, by new differentiated cells, and the process of aging (at least that part of it which is caused by this process) will wind down.