Hey, everyone, welcome to another edition of Wisdom Wednesdays, and welcome back to our ongoing journey which is almost complete about the hallmarks of aging. So today we're doing eleven out of twelve and we're going to talk about macro autophogy commonly just referred to as autophogy. That is a cellular process that is fundamental to staying biologically young, yet it often gets overlooked in aging discussions. And autophogy literally means self eating, but in the best possible way, and it's basically an internal clean up mechanism by which our sales break down and recycle damage proteins and dysfunctional organelles. They're like bits bits of the sale, such as mitochon and other accumulated metabolic junk. And when this system starts to break down, as it does when we age, the consequences show up virtually in every organ system in the body. So let's explore it in a little bit more depth. Basically, autoplogy is a cellular housekeeping process, and it's the mechanism by which cells degrade and recycle internal components, helping to maintain balance and resilience within cells and specifically in macroautoplogy.

Hey, everyone, welcome to another edition of Wisdom Wednesdays, and welcome back to our ongoing journey which is almost complete about the hallmarks of aging. So today we're doing eleven out of twelve and we're going to talk about macro autophogy commonly just referred to as autophogy. That is a cellular process that is fundamental to staying biologically young, yet it often gets overlooked in aging discussions. And autophogy literally means self eating, but in the best possible way, and it's basically an internal clean up mechanism by which our sales break down and recycle damage proteins and dysfunctional organelles. They're like bits bits of the sale, such as mitochon and other accumulated metabolic junk. And when this system starts to break down, as it does when we age, the consequences show up virtually in every organ system in the body. So let's explore it in a little bit more depth. Basically, autoplogy is a cellular housekeeping process, and it's the mechanism by which cells degrade and recycle internal components, helping to maintain balance and resilience within cells and specifically in macroautoplogy.

Parts of the cell.

Parts of the cell.

As I said earlier, like damage mitochondria, are aggregated proteins.

As I said earlier, like damage mitochondria, are aggregated proteins.

What happens is they get wrapped.

What happens is they get wrapped.

In a membrane to form this compound called an autophagisome, and that then infuses with something called a lysisome, and the contents then are either.

In a membrane to form this compound called an autophagisome, and that then infuses with something called a lysisome, and the contents then are either.

Broken down or reuse used and removed.

Broken down or reuse used and removed.

And it's basically our body's way of doing recycling. And it's very very clever because what it does is it actually keeps the energy going in the cell and the process is tightly regulated by nutrient sensing pathways like m tour which we've talked about before, and MPK or amp kiness and when energy is low or our cells are under stress, MPK is activated and that inhibits m tour, therefore inducing autopogy. So, if you can remember from previous podcasts, m tor stimulates growth, AMPK stops that growth and activates this autoplogy, and it's basically a way that we can survive at a cellular level in times of low energy or low stress. And it's a big deal because it really is essential for us responding to stress, detoxifying the cell and even defending against pathogens. And it is really key for protecting our brain, for muscle maintenance, for immune system regulation, and for metabolic balance.

And it's basically our body's way of doing recycling. And it's very very clever because what it does is it actually keeps the energy going in the cell and the process is tightly regulated by nutrient sensing pathways like m tour which we've talked about before, and MPK or amp kiness and when energy is low or our cells are under stress, MPK is activated and that inhibits m tour, therefore inducing autopogy. So, if you can remember from previous podcasts, m tor stimulates growth, AMPK stops that growth and activates this autoplogy, and it's basically a way that we can survive at a cellular level in times of low energy or low stress. And it's a big deal because it really is essential for us responding to stress, detoxifying the cell and even defending against pathogens. And it is really key for protecting our brain, for muscle maintenance, for immune system regulation, and for metabolic balance.

So it's widespread throughout the body.

So it's widespread throughout the body.

And when it declines with age, it is associated with a protein build up, and that in the brain contributes to Alzheimer's and Parkinson's. You'd have heard me talk about TAUL proteins in the brain. It also contributes to immune dysfunction when it goes wrong, Waker stress responses reduced the ability to remove defective mictochondria and then accelerated organ degeneration. So you can see there's a number of mechanisms by which it contributes to accelerated aging, and as well as affecting neurodegeneration and immune agen it also contributes to liver dysfunction because partasites rely heavily on a hoopogy to manage what's called lipid overload. And it also contributes to muscle loss because damage proteins and mitochondria build up in muscle cells, empowering muscle regeneration. And basically, just think of it like the janitor of your body, and when the janitor goes on strike, the whole building aka, your body starts to suffer.

And when it declines with age, it is associated with a protein build up, and that in the brain contributes to Alzheimer's and Parkinson's. You'd have heard me talk about TAUL proteins in the brain. It also contributes to immune dysfunction when it goes wrong, Waker stress responses reduced the ability to remove defective mictochondria and then accelerated organ degeneration. So you can see there's a number of mechanisms by which it contributes to accelerated aging, and as well as affecting neurodegeneration and immune agen it also contributes to liver dysfunction because partasites rely heavily on a hoopogy to manage what's called lipid overload. And it also contributes to muscle loss because damage proteins and mitochondria build up in muscle cells, empowering muscle regeneration. And basically, just think of it like the janitor of your body, and when the janitor goes on strike, the whole building aka, your body starts to suffer.

So let's talk.

So let's talk.

About ways that we can boost autopogy science backed ways. The first one no prices for guessing is exercise. It is a natural autopogy enhancer. When we exercise sells sense this energy stress because at PAI drops when we're exercising, and then amp rises and that activates amp kind is leading to mpt or inhibition and autopogy induction. And so basically the key mechanisms are as I said, the AMPK activiation and inhibiting m tour but then reactive oxygen species production that actually signals us to do a cellular cleanup. And then mild kinds, which I've talked about before. These magical molecules released from muscle. They have systemic anti inflammatory effects. So there's a really complicated process that actually goes on. And in studies of older mice, exercise actually restored autophagic fluss in sorry autophagic flux in muscles, improving strength and regeneration. And in the brains of the mice it boosted clearance of dysfunctional mitochondria and synaptic proteins, which is key for cognitive health. The next thing is fasting and calorie restriction, and that kind of acts as a master switch for autopogy.

About ways that we can boost autopogy science backed ways. The first one no prices for guessing is exercise. It is a natural autopogy enhancer. When we exercise sells sense this energy stress because at PAI drops when we're exercising, and then amp rises and that activates amp kind is leading to mpt or inhibition and autopogy induction. And so basically the key mechanisms are as I said, the AMPK activiation and inhibiting m tour but then reactive oxygen species production that actually signals us to do a cellular cleanup. And then mild kinds, which I've talked about before. These magical molecules released from muscle. They have systemic anti inflammatory effects. So there's a really complicated process that actually goes on. And in studies of older mice, exercise actually restored autophagic fluss in sorry autophagic flux in muscles, improving strength and regeneration. And in the brains of the mice it boosted clearance of dysfunctional mitochondria and synaptic proteins, which is key for cognitive health. The next thing is fasting and calorie restriction, and that kind of acts as a master switch for autopogy.

Fasting.

Fasting.

Prolonged fasting is one of the most potent natural ways to activate autopogy and the energy deficit active. It's AMPK, suppresses m tour and boost suritans and they all drive autophogy. And then the key benefits of that is increased lifespan in model organisms, protection against neurodegeneration, enhanced intestinal and hemopoetic stem cell function, which we talked about last time, and short term fasting of twenty four to forty eight hours has actually been shown to double stem cell activity in the gut and immune system via autoplogy pathways. And then if you do a more prolonged fast of three four days or more, that enhances mitophagi and that's the clearing of damage mitochondria. It also improves metabolic flexibility and has rejuvenating effects on the immune system. Quite a lot of studies have now shown that this happens in both animals and in humans. The third way actually just on the fasting thing. If you exercise in the fasted state, it also enhances autopogy within muscle cells. Only within muscle cells, and that's just like an overnight fast and then going and doing some morning exercise, so that can be really useful for our muscles. And then the third way, which is kind of linked to fasting a little bit, is ketones and they actually fuel clean up and resilience inside our cells. So when we are fasting or on a low carb diet, our body produces ketone bodies such as beta hydroxy puryate, and they act as a signaling molecule for longevity. And we know just if you take beta hydroxy purury it that inhibits what we call his stone deacylases. This is a bit of a mouthful podcast, isn't it, But when you inhibit those things, it actually increases our topogy, gene expression and beta hydroxy butty. It also suppresses inflammation and oxidative stress and enhances and over of our mitochondria, keeping them healthy. And studies show that ke tonges actually mimic calorie restriction and provide neuroprotective effects via enhancement of autopogy. And there's now research going on that maybe you don't have to fast, you can actually take supplemental key tones and get some of these benefits. So let's talk about stuff that's on the horizon or that's being tested or proven right now around autopogy. One you'll not be surprised to hear if you've listened to previous podcast is rapamiacin that inhibits m tour C one and that's one of the central pathways for suppressing autoplogy because it's.

Prolonged fasting is one of the most potent natural ways to activate autopogy and the energy deficit active. It's AMPK, suppresses m tour and boost suritans and they all drive autophogy. And then the key benefits of that is increased lifespan in model organisms, protection against neurodegeneration, enhanced intestinal and hemopoetic stem cell function, which we talked about last time, and short term fasting of twenty four to forty eight hours has actually been shown to double stem cell activity in the gut and immune system via autoplogy pathways. And then if you do a more prolonged fast of three four days or more, that enhances mitophagi and that's the clearing of damage mitochondria. It also improves metabolic flexibility and has rejuvenating effects on the immune system. Quite a lot of studies have now shown that this happens in both animals and in humans. The third way actually just on the fasting thing. If you exercise in the fasted state, it also enhances autopogy within muscle cells. Only within muscle cells, and that's just like an overnight fast and then going and doing some morning exercise, so that can be really useful for our muscles. And then the third way, which is kind of linked to fasting a little bit, is ketones and they actually fuel clean up and resilience inside our cells. So when we are fasting or on a low carb diet, our body produces ketone bodies such as beta hydroxy puryate, and they act as a signaling molecule for longevity. And we know just if you take beta hydroxy purury it that inhibits what we call his stone deacylases. This is a bit of a mouthful podcast, isn't it, But when you inhibit those things, it actually increases our topogy, gene expression and beta hydroxy butty. It also suppresses inflammation and oxidative stress and enhances and over of our mitochondria, keeping them healthy. And studies show that ke tonges actually mimic calorie restriction and provide neuroprotective effects via enhancement of autopogy. And there's now research going on that maybe you don't have to fast, you can actually take supplemental key tones and get some of these benefits. So let's talk about stuff that's on the horizon or that's being tested or proven right now around autopogy. One you'll not be surprised to hear if you've listened to previous podcast is rapamiacin that inhibits m tour C one and that's one of the central pathways for suppressing autoplogy because it's.

A growth pathway.

A growth pathway.

Rapimiasin extends lifespan in mice. It's now being studied in dogs. Matt Chamberlin is doing a big study on that seeing if it can enhance the lifespan of dogs, and I think that study is due to be released in the next year or so. And it's also being tested rapamasin in humans for immune system regeneration or rejuvenation and also Alzheimer's and forcycopedia that loss of bone and muscle. And we'll just see what happens when those studies are published. Then the next one is spermidine.

Rapimiasin extends lifespan in mice. It's now being studied in dogs. Matt Chamberlin is doing a big study on that seeing if it can enhance the lifespan of dogs, and I think that study is due to be released in the next year or so. And it's also being tested rapamasin in humans for immune system regeneration or rejuvenation and also Alzheimer's and forcycopedia that loss of bone and muscle. And we'll just see what happens when those studies are published. Then the next one is spermidine.

So this is a a polyamine if you really interested.

So this is a a polyamine if you really interested.

It's found in wheat, germ soy, and age cheese like blue cheese, and it's been shown to boost autophogy and actually has cardiovascar and cognitive benefits and animal studies.

It's found in wheat, germ soy, and age cheese like blue cheese, and it's been shown to boost autophogy and actually has cardiovascar and cognitive benefits and animal studies.

You can buy that as a supplement.

You can buy that as a supplement.

And then there's resveratrol that's found in red wine. There's debit about whether it activates surtins, but it does seem to mimic some fasting effects and possibly can enhance mitochondria, biogenesis and autophogy. But like I said in previous podcasts, it has been proven that it actually doesn't extend lifespan. Other things that are being studied at met Foreman, and that's a diabetes drug that some people think has longevity potential. It's been shown to activate amp kinds and improve metabolic health, and people think that it indirectly supports autoplogy. So watch this space on met Foreman. And then there's a couple of other molecules that are being tested. One is Trehallows that's a kind of a sugar molecule that induces autoplogy independent of the m to our pathway. And then something called another mouthful to finish the podcast, peptides like FOXO four d RII. Who the hell comes up with these names? This is an experimental agent that induces selective autoplogy in these sinescent or zombie sales.

And then there's resveratrol that's found in red wine. There's debit about whether it activates surtins, but it does seem to mimic some fasting effects and possibly can enhance mitochondria, biogenesis and autophogy. But like I said in previous podcasts, it has been proven that it actually doesn't extend lifespan. Other things that are being studied at met Foreman, and that's a diabetes drug that some people think has longevity potential. It's been shown to activate amp kinds and improve metabolic health, and people think that it indirectly supports autoplogy. So watch this space on met Foreman. And then there's a couple of other molecules that are being tested. One is Trehallows that's a kind of a sugar molecule that induces autoplogy independent of the m to our pathway. And then something called another mouthful to finish the podcast, peptides like FOXO four d RII. Who the hell comes up with these names? This is an experimental agent that induces selective autoplogy in these sinescent or zombie sales.

So in closing.

So in closing.

Firstly, I promise that next week's the last one mould have so many big words. But closing thoughts is that when this macrotophagy becomes disabled or doesn't work well, it's like a broken recycling plant inside yourselves and without it, damage starts to pile up, leading to dysfunction, disease, and faster aging. But the good news is that you can induce ortophogy naturally through exercise, prolonged fasting, and perhaps a kidogenic diet or ketone supplements, And there are some pharmological tools that are being tested that seem to have quite a bit of promise.

Firstly, I promise that next week's the last one mould have so many big words. But closing thoughts is that when this macrotophagy becomes disabled or doesn't work well, it's like a broken recycling plant inside yourselves and without it, damage starts to pile up, leading to dysfunction, disease, and faster aging. But the good news is that you can induce ortophogy naturally through exercise, prolonged fasting, and perhaps a kidogenic diet or ketone supplements, And there are some pharmological tools that are being tested that seem to have quite a bit of promise.

And with most of the aging.

And with most of the aging.

Intervention, the best strategy is combining lifestyle and science backed tools to actually protect against this decline. So that's it for this week. In the next week session, the last one, it's going to be my favorite, we're going to talk about mitochondrial dysfunction. But until then, you're going to amuse yourself by re listening to this podcast to see if you can work out what the hell I said.

Intervention, the best strategy is combining lifestyle and science backed tools to actually protect against this decline. So that's it for this week. In the next week session, the last one, it's going to be my favorite, we're going to talk about mitochondrial dysfunction. But until then, you're going to amuse yourself by re listening to this podcast to see if you can work out what the hell I said.

Catch you next time,

Catch you next time,