Dancing Between Purity and Pollution

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Readers Summary

  1. What defines human aging?
  2. Are free radical always bad?
  3. How does mitochondria effect life and death?
  4. How do mitochondria interact with apoptosis, autophagy, and telomeres?
  5. Why do Okinawans really live long?

Mitochondria can allow life or kill us.  Mitochondrial DNA has only 37 genes.  From those 37 genes comes just 13 proteins.  Those 13 proteins code for the electron chain transport complexes.  The remainder of the genes code for tRNA.  Mitochondria also cant grow outside the cell.  They require the 30,000 genes in the nucleus to make up another 1500 proteins for them to function.  Mitochondrial DNA and nuclear DNA have to have precise lock and key fit to generate energy production.  If not, the cell eliminates itself by apoptosis (levee 19) fast.  If It works well,  this combination is naturally selected for future cell division to generate energy.  Aging is quantified by how “leaky” our mitochondria are to free radicals at complex ones in electron chain transport.  Their own DNA is adjacent to the first complex in electron chain transport.  So the more leakage,  the more damage is done to its DNA and energy production will fall.  Moreover,  that is the signal to make more mitochondria or undergo cell suicide!  This first complex (NADH) is by far the most leaky to free radicals of all the complexes.  This paradox of fate caused evolution to select for 10-20 copies of mitochondrial DNA in each cell to sustain energy production of an organ in question.  So mitochondria can breathe life into us and end it based upon how many good mitochondria we have in a tissue.

So as we age, our mitochondria generate many mutations due to the free radical damage at complex one.  This especially occurs in active tissues like the heart or brain.  These ironically undermine the metabolic function of the organ in question by depleting energy sources.  The only way to overcome this is to recreate new mitochondria by biogenesis.  In essence, we need to create new power plants constantly.  We face a problem when we run out of perfectly functioning mitochondria and have to begin to clone genetically damaged ones because the well is dry.  When this happens, the cells in question have to commit suicide called apoptosis.  So as a tissue ages, the cumulative mitochondrial damage is removed by apoptosis and we never see evidence of this genetic damage in older organs like the brain or heart when we look for it.  The remaining good cells in the heart are saved by autophagy.  Autophagy is self repair of the remaining good cells as we age.  The cells removed by apoptosis are turned to scar.  This is precisely how the human heart ages.  We see it get larger with scar and have smaller numbers of cardiomyocytes that get recycled because there are no other stem cells left to replace the old heart muscle cells.  With those losses we also lose function as well.  These losses are very tolerable in younger tissues because there are so many copies of mitochondrial DNA to choose from.  But as one ages, the cells get closer to their ends of replication.  We call that end their apoptotic threshold or Hayflick limit.  This occurs when the cells telomeres are too short for cell division.  The Hayflick limit is the amount of times a cell can divide before it has to die by apoptosis.  This number is determined by the length of our telomeres.  Telomeres can be thought of like the ends of a shoelace.  They are an extra piece of DNA that is sacrificed in every cell division.  As a cell divides the telomeres get shorter and we age in corresponding fashion.  Once the telomere is short,  the cell no longer can divide and enters a phase called senescence.  Senescence correlates with aging.  This mechanism exists to prevent genomic instability and the development of cancer.  If a cell divides with a short telomere the chance of developing cancer rises exponentially.  Therefore, “mitochondrial leakiness” is the key determining factor in aging.  The more leakiness that occurs at the first complex causes the generation of more free radicals which damages subsequent copies of our mitochondria DNA to generate cellular energy.

When I was in medical school, we were taught to believe that free radicals were bad for cells.  This was a tenet of the mitochondrial theory of aging.  It appears that is more dogma that is now updated by biology’s truths.  It now appears that biology uses this free radical generation to eliminate bad mitochondria and stimulate the genesis of new good mitochondria to make energy for cells.  This is a great thing for a cell’s longevity.  So antioxidants won’t prolong your life, in fact, they could shorten it because it interferes with the sensitivity of mitochondrial signaling.

Animals that leak free radicals faster tend to have shorter lifespans.  Rodents are a good example.  Birds and humans, however, do not leak as fast as rodents and therefore they have longer lifespans.  The key point here is that to age well and live longer. the strategy should be to restrict free radical leakiness of our respiratory chains.  In 1998, Tanaka reported in The Lancet on the super-centenarians of Okinawa.  He found that a lot of them had a single base change in subunit one of the respiratory chain where most leakiness occurs in humans.  That one base change was responsible for their longevity.  This was irrespective of their diets and life style.  Many other authors have tried to link the Okinawans longevity to their lifestyle but it now appears that this blue zone occurs because that one base change makes their mitochondria less leaky at complex one.  This allows for less mitochondrial damage and less need for new mitochondria to be made over time to support the organ in question.  In effect, aging slows down for that tissue.  The key it appears to a longer healthier life is having more mitochondria to generate energy and not use up the mitochondria they were born with.

We have already said that leakiness of free radicals causes us to amplify more mitochondria,  so it also stands that to live longer requires us to have a more sensitive detection system to pick up that leakiness signal.  Many diet gurus tout us taking antioxidants in large doses for health.  We now can see this advice runs completely counter to how mitochondria really work.  The intracellular environment requires less antioxidants to make sure the signal is heard and mitochondria can be made when the tissue requires it.  So taking a ton of antioxidants every day may not be the correct thing to do.  This may explain why the studies on exogenous antioxidant use has been so disappointing to so many.

So to live optimally, we see that it is tied to our mitochondria. When they ultimately fail, we die. The strategies we have to optimize ourselves are to decrease the leakiness to free radical at complex one to protect our mitochondrial DNA from damage.  Or we can uncouple our electron chains, to decrease leakiness by using uncoupling proteins as we saw in the leptin blogs.  There is another method that birds and bats use.  They over produce their capacity of mitochondria.  If you have more, you can afford to lose more.  Birds and bats have more mitochondria because they require more energy for flight.  That naturally selected trait has given them their longevity compared to their metabolic rate.

Cites are common to last post.

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  1. Resurgent says:

    Is there any truth to the use of acetyl L-carnitine and alpha lipoic acid specifically for mitochondrial health.

    • The Acetyl L carnitine is transported outside the mitochondria where it converts back to the two constituents. The L-carnitine is cycled back into the mitochondria with acyl groups to facilitate fatty acid utilization, but excess acetyl-CoA may block it. Excess acetyl-CoA causes more carbohydrates to be used for energy at the expense of fatty acids. ALA effects on the mitochondria are controversial. Its has a much bigger effect on the hepatocytes and acts like curcumin and resveratrol.

      This is why carbs turn off fat burning at the mitochondrial level. Insulin is always blamed, but in my view this is the most important reason people cant keto adapt on a metabolic level unless they go low on their epi-paleo template.

  2. Diane S says:

    Jack I have read the Leptin Book, and now we are more than half way threw the Paleo solution. Very confused! They are completely contradictary! Are we supposed to follow the Leptin way first? Byron says to eat foods that are totally not Paleo? I have been feeding all of us bacon & 4 omega3 eggs every morning for 3 wks,Leptin says dairy is good Paleo says no bacon or dairy at all, which is it? HELP!!!

  3. More reading material that supports my belief about this levee in the quilt…….read on http://www.huffingtonpost.com/joel-fuhrman-md/metabolism...

  4. @Diane…..The paleo solution is the the fuel you eat. How you eat that food is what is in the leptin book. Its simple. breakfast should be largest meal of day loaded with protein and fat. 50-70 gms of protein for most obese folks. Limit carbs to 25 grams a day. Dont go above 50 if you can help it. No snacks ever. That is it. Simple.

  5. Diane S says:

    Ok, so I will keep doing what I have been. In week 4 Jack & I have lost 22lbs!! 🙂

    Thank you!!

  6. Zack leman says:

    So if too much antioxidants can be harmful does supplementing with the liposomal glutathione that Dave Asprey recommends dangerous or is Glutathinone a different story? Thanks. I know that liposomal glutathione is absorbed well by the body.

    • @Zack it might be if your a great methylator…..but so few humans are. Get your 23andme.com test to see if you are the owner of a good detox system in your liver or not. Very few are.

  7. Zene Kamili says:

    Hello Dr. Kruse,
    This is my first comment/post to your site ever. I have been reading lots of your sites and your book lately. Presently, I am finishing the Cold Thermogenisis 3 Blog’s comments. And one particularly comment that intrigued me was the one about the Okinawan’s longevity. Your response was:

    Okinawans longevity is tied to a SNP that reduces their leakiness at cytochrome one and nothing to do with their diet as is often reported. NOT TRUE. I covered that long ago here. http://jackkruse.com/why-we-die-and-why-we-live/ .

    This led me here to this page. My question is: Is this just a genetic trait that they have or is there something that can be done by any other person to reduce their own leakiness at cytochrome one. What causes this be for this group of people? I admit, I don’t have much understand of what cytochrome 1 actually is and how it functions.

    Enjoy reading your ideas. Keep it up!

    • It is a founders effect of being genetically isolated on their island for thousands of generation. I believe Tanaka wrote the paper in a British journal in 1998 or 99 if my memory is correct.

      • Zene Kamili says:

        Thank you for your answer to my question, I appreciate it! I attempted to hunt down Tanaka’s papers without success. However, in the meantime since I last posted this question, I have been reading more of your thoughts and theories. You emphasize that epigenetics supersede genetics. I think that I understand the priority that founders genetic effect has on biology based on your idealism. So, in this case, genetics trumps epigenetics? I am also assuming, based on my reading since my last post that the light situation plays a dominant role in their longevity. I am also beginning to notice the trend in blue zones that they have superior environments in respect to light exposure and lifestyles lived that correspond to taking advantages of this.


  1. […] the day while energy is being made to explore the environment the cell is more oxidized because of increased leakiness of the mitochondria at cytochrome one. Remember the more we leak electrons from our mitochondria the faster we age and the more neolithic […]

  2. […] be measured in their telomere lengths.  Why does this happen?  Carb training increases ROS at the first cytochrome of mitochondria when we make ATP from […]

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