The Contesting Theories For Ageing
This might be the elixir of life we’ve been chasing in alchemy labs since the days of the Ancient Greeks. Or at least, it’s the gateway to living long, and living well.
All this time we’ve been duped into thinking we’re the protagonists of this story, and it turns out we’ve been playing hosts for the star players this whole time. The mitochondria don’t exactly need introductions, they got plenty of press in school biology textbooks. These are the powerhouses of the cell, 10 million billion furnaces working to keep the lights on. These guys are everywhere, in every tissue of the body, dwarfing your own cells. But their significance has still been woefully understated.
There hasn’t been a shortage of theories being flung around for the burning question of existence. Why do we age?
Here are a few of the contenders.
The Endocrine Theory – Falling levels of circulating hormones like testosterone and estrogen. Probably invented by your local TRT clinic. But is the cause, or a consequence of ageing?
Wear and Tear Theory – Cells deteriorate over time, gradually pushing you closer to kicking the bucket. Once again, this is more effect than cause.
Telomere Theory – A popular niche these days. These are the caps at the end of chromosomes, that slowly wear down over our lives. This has birthed a few supplements like TA-65, that maintain telomere length. There’s nothing to suggest this isn’t just another episode of quackery designed to sell expensive interventions. For thousands of pounds, you get a little boost to immunity. That’s it. Never mind the fact that you could reproduce the same outcome, at less expense, with exercise.
And to trot out the same conclusion, it’s likely a consequence rather than a source.
But finally, we have the Mitochondrial Theory, the idea that reactive oxygen species (ROS), damages the mitochondria, causing them to mutate and deplete. It’s a slow, sure process that inevitably winds up with weak mitochondria that are unable to provide adequate energy supplies. Tissues die off, organs get scuttled to half-capacity, the body gets slower, weaker, more fragile.
It’s a solid theory, reinforced by the fact that it has a definitive cause. If you produce excessive amounts of ROS, stuff gets broken. Do it often enough, and it outstrips the body’s ability to fix itself. And the appearance of ROS itself? It’s a perfectly normal mechanism, vital actually, because it acts as a message to the control hubs to produce more energy. But there are a few things that turn the dial a little too far, and it all happens in the microcosm of the mitochondrial cell.
By getting to grips with the mechanisms at play, you can understand just how the process of ageing works. And more importantly, how we can minimise damage and reinforce the structure of the mitochondria.
The Origins Of Mitochondria
Chronic disease, lethargy, imbalances, wear and tear, all can be traced back to dysfunction at the mitochondrial level. This is, effectively, the metabolic epidemic. This article isn’t meant to share out the secret to immortality, but it’s certainly a route for living and thriving over an extended lifespan. Healthy mitochondria make for a body that’s running in peak condition and free of the usual signs of rapid ageing.
So we’ll swivel back to those mitochondria-based ageing factors, and set up strategies for combating each of them. You might want to get a strong brew going, or dunk under a cold shower first, because this is about to get a little deep in the biochemistry weeds. But if my articles on saturated fat and dopamine are anything to go by, I’m going to be guilty of dumbing down complicated mechanisms, so don’t worry too much.
To give a brief primer on the world of mitochondria, it essentially runs a symbiotic racket alongside your cells. Some 1.45 billion years ago, a rogue bacteria entered a eukaryote. One thing led to another, evolution steadily picked up on this happy accident, and planetary life upsized. All animal species contain mitochondria. As do plants, but they rely more on chloroplasts instead.
The partnership enabled life to take the many forms we have today. Both are reliant on each other to ensure their survival. The mitochondria feed off incoming carbohydrates and fats and produce ATP, the standard unit of energy in the body. The eukaryote can then make use of the energy for its various functions.
As energy feeds into the mitochondria, they have to head through the Electron Transport Chain in order to be converted to ATP. When plenty of energy is coming in, ROS is produced as a signal to use ramp up the process so the mitochondria don’t get overwhelmed. As you might guess, the issue arises when it gets hyperinflated.
When ROS goes out of control, the mitochondria get damaged. Naturally, they have systems in place to manage a crisis, such as when mutated cells commit suicide rather than risk getting replicated.
But when this crisis is occurring hundreds of times a day, every day, the stress outstrips the mitochondria’s ability to respond. The process repeats endlessly, and your tissues are left with fewer and fewer functioning mitochondria. That in turn means the tissues don’t get enough energy. In places like the heart, that can be fatal.
So the goal here is to ameliorate the destructive results of ROS, reducing it to a rate that the mitochondria can cope with. Any improvements on this microscopic front, will pay up with dividends that extend far beyond longevity. Healthy mitochondria can power your performance to new levels, enhance fat loss, and cut right down on systemic inflammation.
Too Much Energy Coming In
Chuck too much down the ETC, and ROS racks up. This is a state that’s unfortunately triggered all too often by the modern diet. Its high carb makeup funnels the mitochondria with inefficient energy. Whereas glucose molecules produce 38 ATP, a fatty acid gives up 139. Piling on the sugar just means you’re adding to the traffic clogging up the ETC.
The fact is, glucose was never a fuel we were meant to eat in significant doses. Physiological insulin resistance is a human phenomenon that allows the body to block the muscles from taking up glucose, sparing it for the few tissues that actually need it, such as the testes. Our evolutionary adaptation towards fat is reflected at the mitochondrial microcosm. If we can reduce the glucose spikes and increase quality fat intake, the ETC is going to run a lot smoother.
Another obvious route here, and the only technique proven to extend the human lifespan, is a calorie deficit. Fewer compounds coming in, less ROS being produced. A temporary curfew to restore order. I’ve preached the need to match seasons of feasting with seasons of fasting, and it certainly seems to pan out at this level.
Too Little Energy Going Out
This is known as the athlete paradox, where the active folk are using plenty more oxygen, one of the inputs to ETC, and therefore have elevated ROS. But these athletes are healthier than the sedentary versions with less ROS. This can be explained by the increase in energy expenditure. More is being used, even after exercise, and that prevents the ETC traffic jam. The newly minted ATP always has a place to go to.
Exercise, in particular HIIT-style cardio, also promotes mitochondrial biogenesis, where the cells divide and increase. Think of it as the cellular version of hypertrophy gains. More mitochondria is obviously going to be a huge asset in the fight against the attritional forces.
Fasted training is an excellent way to stimulate biogenesis, because it pairs up exercise with another big player in the mitochondria game. We’ll be getting to it soon enough.
Dysfunctions In The Electron Transport Chain
The ETC itself isn’t one smooth route, but made of four complexes, where incoming electrons jump from one to the next. Each of those complexes need certain compounds in order to function. And if the complex is bust, the electrons don’t get to the next one, and high ROS results.
One big player here is Coenzyme Q10, which you may have caught up with in my crispy lamb heart recipe. CoQ10 can actually be synthesised with the body, but that production declines with age, and people past 50 can be horribly deficient in this critical compound. It’s also lost during exercise, so it makes sense to include it in your diet in some shape or form, even if you’re brimming with youth.
Magnesium also plays a key role in creating ATP, and is deficient in a big chunk of the world’s population, including a whopping 50% of Americans. It’s worth noting that regular lifters may need to double up on their magnesium intakes, as this mineral is also integral to the stretching of muscles.
The B vitamins impact energy metabolism in a big way, including the synthesis of several complexes. Carnitine is used as a transporter to bring fatty acids into the mitochondrial membrane. Creatine increases energy efficiency by recycling used ATP. Heme iron moves oxygen into cells, and contributes to the construction of the complexes.
And you might be wondering why we can’t just fix this whole ROS dilemma by consuming antioxidants. The problem here is that you need it to target the mitochondria, which your standard blueberry does not do. But we do have a special something that has shown the ability to bring its healing effects down to the mitochondrial level.
This would be Alpha Lipoic Acid, best not confused with Alpha Linoleic Acid, as the latter is just a plant Omega 3. Alpha Lipoic Acid, found in red meat and organs, and is contained in the mitochondria. It boosts levels of glutathione, the body’s natural antioxidant, while also enabling the ETC to run smoothly. ALA has been shown in studies to improve mitochondrial function.
Many mitochondria fanatics have their eye on this issue, and arm themselves with supplements to stem the gaps. Personally, I think supplements tend to be ineffective, badly absorbed, and a waste of money. Whereas an ancestral diet, could easily supply those nutrients in bioavailable form for a fraction of the cost of stocking up on various bottles.
All you’d have to do here is get your fill of fat-rich red meat, throw on a few ounces of organs, and all those aforementioned mitochondrial nutrients will have been tackled in the swoop of one dinner plate.
The only exception possibly being magnesium, as it’s been depleted in the soil over recent decades, so the bottom-up supply to beef is going to be hamstrung.
When in doubt, eat the food that have mitochondria. And that doesn’t mean plants, because they don’t respirate all that much. Photosynthesis is more there wheelhouse. So if you want to become a breatharian and live off air and sunlight, then by all means, shoot for the plants instead.
Fragile Cell Membranes
The walls of the mitochondria are all that’s protecting the control hubs from falling prey to inflammatory compounds. Once the mitochondrial DNA (mtDNA) gets damaged, it can mutate and replicate, resulting in exponentially worse outcomes. So you want that wall to be solid, especially in the face of the oxidative damage produced by rampant ROS.
If you’re on a diet high in vegetable oils, you’ll have buffered up your cell structures with dangerously unstable Omega 6 fatty acids. If you were to look at the molecular chain of an Omega 6, such as linoleic acid in the picture above, you’ll see that it has multiple double bonds that give it a bent shape. Those molecules are loose and liable to break.
Amongst all the mischief created by processed vegetable oils, the sensitivity to oxidation is the pick of the bunch. They don’t even get past the packaging and shipping process without falling apart. By the time the spiced-up rapeseed oil enters the digestive tract, it’s already rancid. And you don’t save the situation by going for upmarket cold-pressed versions.
The only real way out of this mess, would be by purging vegetable oils and replacing them with shelf-stable fats that can withstand the pressure of oxidation. But what could that be?
Saturated fats, as seen in stearic acid in the picture, don’t contain double bonds, and hold their shape extremely well. This gives it a natural resistance to oxidation.
Increasing Brown Adipose Tissue
BAT can provide an outlet to siphon off excess calories, when activity alone isn’t enough. And ketosis is certainly one way to increase BAT stores. But there’s another player in town, illustrated by the difference in BAT between Africans living around the equator line, and roaming tribes of Inuits in the polar north.
The former have barely any brown fat, and they also happen to have exaggerated propensities for chronic diseases. Whereas the Inuits have plenty, and metabolic dysfunction is practically non-existent. There’s definitely some weight to this theory.
However, it’s going to be hard to replicate the Inuit experience and gain their metabolic powers without emigrating to Greenland. There is evidence showing cold exposure increasing BAT activation, but it’s probably going to take more than a few cold showers to get there.
My hot take? Get comfortable with the cold, and make the most of the mitochondrial benefits of winter. Turn down the thermostat, start the day with cold showers, and try not to shelter under three layers. Even if it doesn’t end up having a large effect on brown fat, it’s still a natural stress that keeps the body alert and resilient. So take the plunge.
Finally, it’s the evolutionary survival fuel with benefits that span the scope of human metabolism. They might have first entered the public consciousness as the sign of dangerous levels of diabetes, but these molecules are specifically designed to promote health and longevity. In the long age of the hunter, ketones enabled tribes to go weeks without food, without losing the energy they needed to bring down a prime mammoth.
As for these days, ketones provide the antidote to the ROS inflammation purges brought about by a high-carb, high-vegetable oil diet. When a large intake of fats is paired with the absence of carbs, the ketones get upgraded to masters of the fuel chain. They enable the body to clamp down on ROS, by increasing the energy efficiency of the mitochondria, and by acting as anti-inflammatory signals.
Stearic acid in particular, a saturated fat found in red meat and dairy, overloads the ETC and causes it to reverse the flow of electrons. This leads to reduced fat storage and increased mitochondrial uncoupling. In effect, it wastes extra energy as heat, further reducing the traffic in the ETC by adding an extra outlet. This is why you’d feel your body turning into a furnace after devouring a big pile of steak.
The neurotransmitter glutamate, when spiked, causes damage to the mitochondria. And as it so happens, glutamate gets triggered by carb intake. Whereas ketones neuter the inflammatory mechanisms by raising the GABA to glutamate ratio.
Ketones, as a form of hormetic stress, can also increase mitochondrial biogenesis, the friendly feature I set up earlier with fasted training. Because one way to increase your ketones is simply skipping breakfast.
Ketosis, the state where ketones are dominant, also increases the conversion of standard white fat to brown adipose tissue (BAT). This can have extraordinary implications on mitochondrial function, because like stearic acid, it possesses the ability to waste energy as heat.
It has to be said that a ketogenic diet could still contain oxidation-happy vegetable oils, and plant toxins that cause DNA damage. To give just a few examples, polyphenols and goitrogens both cause oxidative damage and deplete the body’s supplies of glutathione. So the ultimate cleaned-up version would be the carnivore template. And amongst all the perks carried by carnivore, spearheading mitochondrial function may well be the standout.
To put all that science in the briefest of actionable steps, mitochondrial health really comes down to living an active ancestral lifestyle, while minimising the classic ROS triggers in the lazy modern version.
- Eat fatty meat, with organs, in order to supply the necessary mitochondrial components.
- Lower carb intake, and eliminate vegetable oils altogether. These otherwise lead to excessive ROS and mitochondria that are liable to break.
- Incorporate ketosis, and cold exposure, as hormetic stressors that cause the mitochondria to adapt and become more resilient.
- Make use of regular hard exercise to stimulate mitochondrial biogenesis, and provide an outlet for incoming energy.
With these steps, the ETC runs smoothly, and ROS isn’t allowed to reach its destructive worst. At this point, you also now know much more about the mitochondria than most. Give yourself a pat on the back.
And I apologise for not coughing up any miracle supplements that can add a decade to one’s lifespan. As of now, natural strategies remain the most effective way to living long, and ending with a spring left in the step. That fact is liable to change with the rate that medicine has jumped over the last few decades, but nature has a habit of getting the last laugh.