Speaker 1: Hey, everyone, welcome to another edition of Wisdom Wednesdays and
Speaker 1: to the last of twelve of our series of anti
Speaker 1: aging strategies. And today we are goining to talk about
Speaker 1: mitochondrial dysfunction, and it's basically.
Speaker 2: The power failure behind aging.
Speaker 1: That's power for people who can't understand my accent, and
Speaker 1: so mitochondrial dysfunction for me is probably the most important one,
Speaker 1: just in my opinion, of those twelve hallmarks of aging,
Speaker 1: because we know that the mitochondria are implicated in almost
Speaker 1: every one of the major causes of death, and they
Speaker 1: are also implicated in pretty much every mental health condition
Speaker 1: that there is. Doctor Chris Palmer, who's a psychiatrist at
Speaker 1: Harvard University, has written a brilliant book called Being Brain Energy,
Speaker 1: and basically he shows quotes all of the studies that
Speaker 1: show that damaged mitochondria or suboptimal mitochondria are present in
Speaker 1: every mental health condition that there is. Now, let's get
Speaker 1: back to the mitochondria. They are often known as the
Speaker 1: powerhouses of the cell because they create the energy within
Speaker 1: the cell, but their rules extend far beyond energy production
Speaker 1: and understanding how that influences aging and really provides insights
Speaker 1: into how we can maintain our vitality, increase our health span,
Speaker 1: and prevent chronic diseases. So what are they? They are
Speaker 1: specialized organelles. Organell is just a fancy name for a
Speaker 1: substructure of the cell that has one or more and
Speaker 1: are one and more clear functions. And so these are
Speaker 1: specialized organelles within our cells, and they're responsible for producing ATP.
Speaker 1: ATP is the primary energy currency of our cells and
Speaker 1: therefore of us, and they achieve this ATP through something
Speaker 1: called oxidative phosphorolization.
Speaker 2: So there's going to be a few big words. That's
Speaker 2: just a little bit of a warning.
Speaker 1: But that's basically how we convert nutrients from food into energy,
Speaker 1: and it's through something called or part of it's through
Speaker 1: something called the CREB cycle. So cells with high energy
Speaker 1: demands think about neurons in the brain and muscle cells,
Speaker 1: they have numerous mitochondria to meet their energy needs. So
Speaker 1: the more energy hungry a cell is, the more mitochondria
Speaker 1: they tend to have. But they don't just the energy production.
Speaker 1: They're also involved in critical processes like calcium signaling, which
Speaker 1: is really important for keeping us alive, apoptosis, which is
Speaker 1: that programmed sale death that we talked about in previous episodes,
Speaker 1: and also the generation of reactive oxygen species. And their
Speaker 1: unique feature is that they actually possess their own DNA
Speaker 1: called mitochondrial DNA, and it's inherited maternally, so it comes
Speaker 1: from the mum and that encodes essential components.
Speaker 2: For their function.
Speaker 1: And this really sets your mitochondria out from everything else,
Speaker 1: the fact that they have their own DNA which you
Speaker 1: actually get from the mother. And let's talk about mitochondrial
Speaker 1: dysfunction and why it's important in aging. So as we
Speaker 1: age this, the efficiency of our mitochondria actually declines, and
Speaker 1: that leads to reduce the AT production atp sorry production
Speaker 1: and increased reactive oxygen species generation. If you remember reaction
Speaker 1: of oxygen species, they can create inflammation and all sorts
Speaker 1: of nasty things. They basically cause oxidative damage to cellular
Speaker 1: components including lipids, proteins in DNA within the cell and
Speaker 1: that contributes to cellular senescence and tissue dysfunction. So if
Speaker 1: you remember back cellular sinescence, that's like the zombie cells.
Speaker 1: So basically, when your mitochondria loser efficiency, we get more
Speaker 1: damage inside the cell and the cell turns into zombie cells,
Speaker 1: and this decline in mitochondrial function is associated with a
Speaker 1: whole host of age related diseases such as metabolic syndrome,
Speaker 1: and metabolic syndrome basically increases your risk for a huge
Speaker 1: amount of diseases, including cardiovascular disease, the biggest killer, and
Speaker 1: we know that in powered mitochondrial function, it disrupts energy metabolism,
Speaker 1: contributes to insulin resistance and obesity, which are hallmarks of
Speaker 1: metabolic syndrome, but also kind of mitochondrial function and contributes
Speaker 1: to neurodegenerative diseases because are neurons, because they're so energy hungry,
Speaker 1: they are particularly vulnerable to mitochondrial dysfunction. And we know
Speaker 1: now that defective mitochondria can lead to synaptic failure and
Speaker 1: the death of neurons, as we see in Alzheimer's disease
Speaker 1: and Parkinson's disease. And the other big thing that it
Speaker 1: contributes to is cardiovascular diseases. So mitochondal dysfunction in cardiac
Speaker 1: cells impers your heart function and contributes to hypertension, atherosclerosis,
Speaker 1: and overall cardiovascular disease. And if you take those collectively,
Speaker 1: cardiovascular disease neurodegenerate disease and metabolic syndrome, and in the
Speaker 1: knock on effects of metabolic syndrome, that actually.
Speaker 2: Accounts for a huge portion of death.
Speaker 1: And that's why I think mitochondrial dysfunction is the most
Speaker 1: important hallmark of aging. And we have this theory called
Speaker 1: the mitochondrial free radical theory of aging, and that suggests
Speaker 1: that a cumulative oxidative damage from these reactive oxygen species
Speaker 1: over time leads to the functional decline of our mitochondria
Speaker 1: and that drives the aging process. So let's talk about
Speaker 1: the stuff that we can actually do. And first up,
Speaker 1: of course, is regular physical activity. There is probably nothing
Speaker 1: that you can do better for your mitochondria than regular
Speaker 1: physical activity.
Speaker 2: Engaging in in.
Speaker 1: Regular exercise is a cornerstone for bolstering mitochondrial health. Physical
Speaker 1: activity has been shown over and over again to improve
Speaker 1: mitochondrial function and induce mitochondrial biogenesis, which is the creation
Speaker 1: of new mitochondria.
Speaker 2: And so it has two things.
Speaker 1: It enhances the efficiency of your existence mitochondria and it
Speaker 1: creates new mitochondria. And this adaptation is crucial for meeting
Speaker 1: increased energy demands and improving our metabolic health.
Speaker 2: And we know that.
Speaker 1: Both aerobic training, particularly zone two, which is that's that
Speaker 1: heart rate of sixty to seventy percent of your max.
Speaker 1: But from a non technical perspective, you're exercising, you can talk,
Speaker 1: but you can't sing, So you can talk in sentences,
Speaker 1: but you're kind of breathing heavily and you can't sing.
Speaker 1: If you can sing, you're in zone one. If you
Speaker 1: can't talk in sentences, you're in zone three.
Speaker 2: A higher heart rate zone.
Speaker 1: And we know that this zone two, you it's basically
Speaker 1: where aerobic metabolism is dominant, and that has been shown
Speaker 1: to improve our mitochondrial health, can contribute a little bit
Speaker 1: to mitochondria biogenesis. And interestingly, I read a study recently
Speaker 1: where they took a bunch of people who weren't fit,
Speaker 1: and they put half of them straight into resistance training,
Speaker 1: and half of them they did eight weeks of aerobic
Speaker 1: training in zone two before they went into resistance training.
Speaker 2: And then they looked at their.
Speaker 1: Strength training gains and muscle sized gains, and it turns
Speaker 1: out that the people who'd done the aerobic training first
Speaker 1: actually increased their strength and muscle maths quicker than the
Speaker 1: people who went straight into the resistance training. And the
Speaker 1: thinking is the aerobic training gave them a better functioning
Speaker 1: mitochondria and some more mitochondria, and then that translated to
Speaker 1: quicker benefits from the strength training. So let's talk about
Speaker 1: high physical activity. Actually, oh sorry before we do that.
Speaker 1: And high intensity interval training has shown to be very
Speaker 1: very potent in stimulating mitochondrial biogenesis of the creation of
Speaker 1: new mitochondria. So let's talk about the mechanism. One is AMPK,
Speaker 1: and so basically AMPK stimulates mitochondrial biogenesis and enhances oxidative metabolism.
Speaker 1: And the other thing, again we're getting a bit giky.
Speaker 1: Here is PGC one alpha upregulation and PGC one alpha
Speaker 1: If you really want to know what it is, it's
Speaker 1: perioxysome proliferator activated receptor gamma coactivator one alpha, and this
Speaker 1: is a master regulator of mitochondrial genesis. And this PGC
Speaker 1: one alpha pathway is hugely important in our health and
Speaker 1: studies have shown as I said, that both aerobic training
Speaker 1: and high intensity interval training and resistance training improves our
Speaker 1: mitochondrial content and function in our muscle, leading to improved
Speaker 1: intinal insensitivity and reduce.
Speaker 2: Risk of metabolic disorder.
Speaker 1: And we also know that fasting and exercise both stimulate
Speaker 1: mitochondria biogenesis and stress resistance in muscle cells and through
Speaker 1: calcium signaling an AMPK activation.
Speaker 2: Right, that's geeky enough for the minute.
Speaker 1: Let's talk about calorie restriction and intermittent fasting, So reducing
Speaker 1: your caloric intake without going into malnutrition or doing implement
Speaker 1: intermittent fasting or time restricted feeding as some people call it.
Speaker 2: They have been associated with.
Speaker 1: Enhanced mitochondrial function and increase lifespan in various species, not
Speaker 1: in humans, I hasten to add. But the mechanisms by
Speaker 1: which this happens is that when we fast, we switch
Speaker 1: from burning glucose to burning fat. This what we call
Speaker 1: metabolic flexibility. And when you switch over to burning fat,
Speaker 1: it actually stimulates the production of ketone bodies like beta
Speaker 1: hydrox computury it and that actually serves as an energy
Speaker 1: substrate and signaling molecule for the mitochondria. And what fasting
Speaker 1: also does is it induces autopogy. I talked about that
Speaker 1: in earlier ones. That's the cellular clean up process by
Speaker 1: which the things inside the sale actually take damage mitochondria.
Speaker 1: This is called mitophagy. And they take that damage mitochondria
Speaker 1: and actually recycle them and create new mitochondria. So this
Speaker 1: is that's the cellular recycling plant that's actually going on.
Speaker 1: And this this is called cyclic metabolic switching theory. It
Speaker 1: suggests that health benefits of intermittent fasting may actually be
Speaker 1: better than those of continuous calorie restriction. And I actually
Speaker 1: think that's a slam dunk because of that interplay between
Speaker 1: ketone metabolism, mitochondrial adaptations, and autophogy.
Speaker 2: And I know I'm getting very.
Speaker 1: Geeky here, but I think it's important to understand these processes.
Speaker 1: Now I link to this, you'll not be surprised to
Speaker 1: hear that if intermittent fasting does this and through ketones,
Speaker 1: going on a ktogenic diet where it's it's high fat,
Speaker 1: low carbohydrate and moderate protein that stimulates beta hydroxy buttyate
Speaker 1: and other ketones which then positively influenced mitochondrial function. And
Speaker 1: we see this a katogenic diet really beneficial for Alzheimer's
Speaker 1: disease in Parkinson's disease, probably because of the impact that
Speaker 1: they have in the mitochondria in brain cells, and the
Speaker 1: mechanisms are very similar. Add to intermittent fasting enhance mitochondrial
Speaker 1: efficiency because the ktone bodies are really an excellent energy source.
Speaker 1: An increase our at B production reduced oxidative stress. But
Speaker 1: beta hydroxy butty in itself has actually been shown to
Speaker 1: stimulate antioxidant defenses, which is really really important. And a
Speaker 1: study combining a ketogenic diet with exercise actually showed that
Speaker 1: there were alterations in mitochondrial function, including increased respiratory what's
Speaker 1: called respiratory control ratio and ATP production in skeletal muscle,
Speaker 1: as well as improvements.
Speaker 2: In metabolic health markers.
Speaker 1: So together with exercise and a ketogenic diet or intermittent
Speaker 1: fasting can be very powerful double wami for your mitochondria.
Speaker 1: Let's talk about pharmacological or supplement interventions. So NAD precursors
Speaker 1: theoretically are good for the mitrochondry because we know NAD
Speaker 1: plus is really important. So compounds that you'll see like
Speaker 1: NMN plastered all over the internet and NR they are
Speaker 1: thought to boost NAD levels. The fact they've been shown
Speaker 1: to actually do that, and that's essential for our mag
Speaker 1: to chondrial function. But if you don't want to spend
Speaker 1: a shitload of.
Speaker 2: Money on NMN and NR.
Speaker 1: You can actually just take some B vitamins because NMN
Speaker 1: and NAR are actually converted in the gut to vitamin
Speaker 1: B three, which is nicotinic acid. And so you can
Speaker 1: either go out and spend a shitload of money on
Speaker 1: NMN and NR, or you can just take vitamin B three.
Speaker 2: I know what I would do.
Speaker 1: Another supplement that's pretty promising, And actually I have started
Speaker 1: playing with this methylne blue because it has been shown
Speaker 1: to actually stimulate the mitochondria through its actions on the
Speaker 1: crab cycle. It actually by cut passes for those who
Speaker 1: are geeky, complexes one in three in the electron transport
Speaker 1: chain and actually stimulates the crab cycle, leading to increased
Speaker 1: ATP production and improves cellular energy metabolism through the mitochondria. Okay,
Speaker 1: now if that's not kiky enough, let's now talk about
Speaker 1: low level light therapy or infrared and near infrared light therapy,
Speaker 1: so near infrared light and that's also known as a photobiomodulation.
Speaker 1: That is basically applying low level red light to near
Speaker 1: infrared light and to stimulate cellular function. And what it
Speaker 1: does is it works on something called cytochrome C oxides
Speaker 1: and that is a key enzyme in the mitochondrial electron
Speaker 1: transport chain. And there is a heap of research now
Speaker 1: I that shows that near infrared light actually boosts the
Speaker 1: function of your mitochondria, and that is something I was
Speaker 1: so convinced by the research. And I have a panel
Speaker 1: that does both red light and near in for red light,
Speaker 1: because the research for me is very very compelling about
Speaker 1: improvements in mitochondrial function. And we are now even seeing
Speaker 1: near infrared light helmets of certain way of lengths significantly
Speaker 1: improving symptoms in both Parkin's disease and Alzheimer's disease. And
Speaker 1: basically what happens is that at light passes goes through
Speaker 1: your skeleton and actually stimulates goes it deep inside of
Speaker 1: your body and stimulates your mitochondria and certain parts of
Speaker 1: the electron transport chain, and that leads to increased energy
Speaker 1: production and improves cellular energy metabolism. And the other thing
Speaker 1: that near infrared light does is it releases nitric oxide,
Speaker 1: and that actually helps to improve blood flow and reduces
Speaker 1: oxidative stress.
Speaker 2: And studies have.
Speaker 1: Shown that infrared light penetrates human tissues and benefits mitochondrial
Speaker 1: function as I say it, and it can improve things
Speaker 1: like mitochondrial dynamics and quality control following ischemia, stroke, cardiac
Speaker 1: arras so I actually was using it post my heart
Speaker 1: surgery and also for overall brain function, cognitive function. It's
Speaker 1: actually been shown to help people recover from straight stroke
Speaker 1: and neuro degenerative diseases. So hink conclusion, lots of big mouthfuls,
Speaker 1: but basically what we know is our mitochondria are absolutely
Speaker 1: key to cellular health and longevity, and doing things like
Speaker 1: regular exercising, intermittent fasting, low carbon particularly keathogenic diets, some
Speaker 1: potential pharmacology, and near infrared light therapy can all really benefit.
Speaker 1: And while studies haven't been established it because they're really
Speaker 1: hard to do, I actually think that these things are
Speaker 1: additive because they work on slightly different pathways in our mitochondria.
Speaker 2: So I think if.
Speaker 1: You're doing all of them, you're going to get better
Speaker 1: benefits than if you're just doing one or two. So
Speaker 1: that's it for this week, folks, Catch you next time.