Hallmark of Aging 7 - Mitochondrial Dysfumction

June 23, 2024

Hallmark of Aging 7, Mitochondrial Dysfunction

You are 10% mitochondria by weight. They are your powerhouses inside each cell where they turn the energy of carbohydrates and fats into carbon dioxide and water. Like a carefully tuned engine they work well when the energized electrons have some place to go...like exercise using up the energy molecule ATP (Tri-phosphate) into ADP (Di-phosphate) that then returns to the mitochondria to be remade into ATP, 10,000 times a day. On a good day, 1-2% of electrons escape and there are layers of protection to capture those errant, loose electrons and neutralize them.

 The first line of defense are the enzymes superoxide dismutase and catalase, that basically capture the electron and plug in into a water molecule to make hydrogen peroxide, or the Hydroxyl ion. But most importantly, they get the loose electrons out of the cell, saving the cell from death. In the extracellular space, the second line of defense is glutathione. That's what glutathione does, it captures peroxide and neutralizes it. Virtually every chronic brain disease has low glutathione because of the ongoing oxidative stress.

In the situation of overwhelming oxidative stress (COVID-19 infection, anesthesia, 4 scoops of ice cream, ) some excessive peroxide makes it as far as the cell wall of the cells where it runs into plasmalogens. Plasmalogens are on the outside surface of every cell and function as the antioxidant of first resort. They also allow embedded proteins to function with blinding speed because of their ability to shapeshift and their liquidity. They snuff out peroxide, but they sacrifice themselves. The membrane loses one molecule at a time. The chemical malondialdehyde is the result of that chemical reaction, peroxide meeting plasmalogen. Virtually every brain disease has elevated malondialdehyde.

Depletion of plasmalogens is the best predictor of how long you live. Period. And it's not just extracellular plasmalogens that are being damaged by oxidative stress. Inside every cell, the mitochondria itself has some 50% of its own internal lipid membranes are made of plasmalogens. They get damaged too.

Here's the rub. Every article I read about mitochondria degrading and having some form of dysfunction dances around the question, "Why?". We can see it happening. We can see the effects of damaged mitochondria. We can try to reconstitute mitochondria, but what are we really doing? We are documenting and observing mitochondria becoming inefficient and losing increasing amounts of electrons, creating a gyre of increasing oxidative stress, depleting their own plasmalogen supply, but also every cell in the body's supply. But no one has gone the next step to study the repair of mitochondria with plasmalogens.

We know mitochondria have a huge proportion of their membranes made up of plasmalogens. On the order of 50% by best recent research. We know every detail of the electron transport chain in the mitochondria that passes on those highly charged electrons from complex to complex, but no one has ever turned and looked at the membranes that are supporting those electron transport chain proteins. If they are losing their plasmalogens, their supporting membranes are becoming stiffer and more rigid. The embedded proteins can't function quite as well. It's just been the last year or two that review articles about membrane function and mitochondrial decline being linked. That's the key to follow.

My hypothesis is exactly that. We die when our plasmalogens run out. Our mitochondria can't keep making energy and the gyre of increasing release of oxygen radicals destroys cells all over the body. Curtains.

www.What will Work for me? There has to be some link between the eerie predictability of longer life with higher plasmalogens. That means shorter life with lower plasmalogens. When our mitochondria stop working, everything collapses. With the advent of plasmalogen supplementation, we have a new dawn of possibilities. I'm eager to see more data. For now, all I see is description of the trouble we are in when our mitochondria go south. We need to learn how to test their resilience and function better. 

Urolithin, labeled Mitopure, is the first product on the market directed at mitochondrial repair. Urolithin was found in pomegranates. I love pomegranates, for the 3-week season, they are available. This is where methylene blue, (yes, the party blue dye you put in the drinks and everyone swimming in the pool gives a clue if they pee in the pool) kicks in. It also bypasses the block that the spike protein of COVID creates in mitochondria. Eventually, we are going to have a better formula on how to get around that aging thing. Right now, our best bet is Prodrome Neuro and Glia. Those two supplements help rebuild your plasmalogen pool, wherever it may be.

References: Cell, MDPI Antioxidants, Frontiers Cell Development Bio.Curr Opin Cell Biol, ,

Pop Quiz

1. What role do plasmalogens play in regard to calming oxidative stress manifesting as elevated hydrogen peroxide?                          Answer: They are the antioxidant of first resort.

2. What proportion of mitochondrial membranes are made up of plasmalogen lipids?                          Answer; On the order of 50%

3. What makes them so valuable in mitochondria?                                Answer: They are the most fluid of membrane lipids and also have the capacity to shape shift. That facilitates the actions of embedded proteins that frequently have to change shape, 100s of times per second.

4. What does urolithin do?                      Answer. It is the first supplement on the market to address biogenesis of revived mitochondria.

5. Where was urolithin first found?                            Answer: Pomegranates.