Hey, everybody, welcome back to another edition of Wisdom Wednesdays and our series on the major hallmarks of aging, And today we are on number ten out of twelve and we're talking about stem cell exhaustion, one of the key drivers of aging that affects tissue regeneration, immune function, and overall vitality. So stem cells you've probably heard of, and they are cells that are essential for repairing and maintaining our tissues. But as we age, their ability to self renew and function declines. And they are two different things, that self renewal and their function, and together these two declines lead to weaker muscles, slower wound healing, immune dysfunction, and increased risk of diseases like osteoporosis and neurodegeneration, and lots of others. But here's the really interesting exciting part. Emerging research is showing that things like exercise, calorie restriction, targeted pharmaceuticals, and even stem cell based therapies can help combat stem cell exhaustion and potentially rejuvenate aging tissues. So let's explore that in a little bit more depth. So, overall stem cell exhaustion occurs to a combination of both intrinsic and extrinsic factors, which means stuff that's inside the body and outside the body. And the first is DNA damage accumulation. Now you're going to notice there are a number of the other hallmarks of aging that play into this, and that's just because the body is a complex ecosystem. So DNA damage accumulation, which is one of the hallmarks of aging in and of itself, but over time, exposure to oxidive stress, radiation and toxins leads to DNA mutations in stem cells right reducing their ability to divide and to regenerate tissues. And then next is telomere shortening because their cells right stem cells also have telemeres and limited division potential, and as their telomeres, remember those protective caps on the chromosomes, As those telomeres shorten, they lose their functionality. Then we have epigenetic changes, which again is another major hallmark of aging, but age related alterations in DNA methylation and histone modifications that we talked about in that episode. They empower stem cell identsity and renewal, and then chronic inflammation, which we have also discussed. The aging immune system secrets. Those pro inflammatory cider kinds that we talked about, and they can disrupt stem cell function and the surrounding niche. And then one that we haven't talked about yet. I'm leaving it to Alaska. It's my favorite, is mitochondrial dysfunction and aging stem cells generate more reactive oxygen species and that then damages the cellular components and accelerates stem cell exhaustion. So they are the major mechanisms by which it happens. Now let's talk about stuff that we can do. So exercise again, you'll be not surprised here. It's one of the most potent tools to maintain and rejuvenate stem cells. And if you think about it, exercise impacted all those other things we talked about, the DNA damage, telomeres, epigenetic changes, the inflammation, and the mitochondria you'll find out. So therefore it's going to play a role both directly and indirectly. So what exercise does, and particularly in muscle sales, it activates what's called satellite sales. These are muscle stem cells, and then enhances our muscle regeneration. Right, that makes sense if you're activating your muscles and from exercise, they are obviously going to look after themselves better. The next thing that exercise does is it promotes hematopoetic try saying that when you're pissed, hematopoetic stem cell function and that improves our immune and our blood cell production. Exercise also enhances neurogenesis the creative new brain cells. I've talked about that ad nauseum on the podcast, and that improves cognition and protects against neurodegenerative diseases. And then exercise also enhances our mitochondrial efficiency again we're going to do a full episode in this, and reduces oxidative stress, helping the stem cells to maintain their function. So evidence for this, there was a study the cell stem cell and find that endurance exercise increases the regenerative capacity of skeletal muscle stem cells by improving mitochondrial function and reducing inflammation. And research in Nature communication and there's a heap of other research around this shows that aerobic exercise and actually other research shows that strength training boosts BDNF, which enhances neural stem cells survival. So we know that bdn F actually peaks around lactate threshold and where you're producing lactic acid that is when we get a big spike and BDNF because lactate actually crosses the blood brain barrier and directly stimulates the production of BDNF, which enhances our neural stem cell survival. So engaging in that mix of resistance training and cardiovascular training, but making sure you're doing some of it high intensity is really really key. Second is about calorie restriction and the different types of fasting. So they have both been shown to extend lifespan in mice and other animals, but also improve stem cell function by reducing metabolic stress and inflammation. And high calorie restriction does it. And also some of the fasting protocols will will do this by enhancing autophogy so that triggers the cellular cleanup process. Remember autophogy is basically a spring clean for your cells and that removes damage proteins and damage mitochondria, helping stem cells to say functional. And the fasting protocols and calorie restriction also increase this stem cell pull and that's been shown in animals and that it prevents this stem cell depletion, particularly in the gut and the hemo hematopoetic system, and it also improves stem cell quiescence. So this quiescence is a kind of a dormant but healthy state, so not sinescence. Member we talked about those zone and it actually makes them more resilient and extends their lifespan. So studying cell metabolism found that short term fasting increased into style stem cell regeneration in aged mice by twofold. And we do have to be aware mice are not always well, they're not humans ever, but we don't see it always being replicated. But these sources of studies can only be done in nice but research in nature demonstrated that lifelong calorie restriction also did that in older animals. But intermittent fasting and the different protocols that we've talked about, there is some evidence that they may activate autoplogy, and particularly in muscle cells, and especially if you go out for a run or do some cardio in a fasted state, there's good evidence that that activates muscle cell autoplogy. But the prolonged fasting, you know, this is the seventy two hour plus that has been shown to trigger stem cell renewal, especially in the immune system, and there's quite a lot of evidence of that even in humans. So let's not talk about M tour inhibitors. Now, we have mentioned these in a previous podcast, but something that is on my radar, which I've talked about, is this M tour inhibitors because this M to our pathway, So M tour stands for mechanistic or mammalian some people say target of wrappamasin and it actually promotes selle growth. But with that metabolism and aging. Now, M tour activation is crucial for muscle growth and immune function, but it's this chronic overactivation that accelerates aging and actually accelerates sem stale depletion. Now, again I mentioned before, we have to be very careful to distinguish between M tour inside the muscle and M tour outside the muscle, because inside the muscle is good thing, but outside the muscle, after we've reached our food age can become problematic over the long run. So ones that are being studied now M toor inhibitors rapam iicin. I've talked about that. That's a very well known M tour inhibitor. It is extended lifespan in animal studies and rejuvenated aged heematopoetic stem cells and there are current trials investigating its potential for improving immune function and reducing age related diseases. And as I've said before, in the Interventions Testing Program, which is a massive program looking at all these particular agents that could extend lifespan done in animals obviously, and the one the big star is rapam iosin and it's been done in nice, it's currently being done in dogs, and if it shows the same protocol then there is good potential for rappamacin to act in humans. There's a lot of people excited about that in the scientific community. And the next one is met foreman. That's a diabetes struggle game. We've talked about this before, but it appears that it may be able to modulate m tour signaling and reduce inflammation, possibly protecting SEM cells, and studies show it improves muscle stem cell function in aging animals, but studies in human show that met forman can inhibit the benefits of exercise, so kind of watch this space. Res Virtual is a polyphenol that's found in red wine and it activates AMPK, which is a longevity pathway and indirectly inhibits SEM tour. Theoretically, supporting stem cell health. But I do want to say that Virtual was shown in the Interventions testing program to have no effect on aging. Whether it's having some effects on stem cells, maybe that's true, but overall in terms of aging, whereas Virtual is not an anti aging therapy, even though it's being promoted all over the internet as one of those. Let's now talk about some potential stuff for the future, which you know is being done in some places. But this is stem cell therapies. And if you live in Australia, good luck trying to get stem cell therapies. But certainly in the United States you can get some some of those commercially, and in places like Mexico and Panama and stuff like that, there's a lot of stem cell therapies going on, and probably some other countries around the world. And so there's different types of stem sale therapies, and I'm not going to go into a massive detail on them, but just as an overview, the first one would be messen chymo or mensynco, depending whether your British or American in terms of your pronunciation. That's missing chymeal sten cell therapy mses from bone marrow fat or umbilical cord have actually been shown to reduce inflammation, promote tissue repair, and improve immune function. And there's current clinical trials in humans testing and missing chymal stem cell therapies for osteoarthritis, neurodegenerative diseases, and immune regeneration. Then the next one is induce plury potent stem cells. So plury potent stem cells. These are cells that have the ability to turn into any cells, but scientists can now reprogram adult cells into stem cells, offering potential for regenerative treatments. And studies show that induced pluri protent stem cells could restore aged organ function, but there are risks like tumor formation that do need to be addressed. Then we have stem cell derived exosomes, so exosomes. Actually did a podcast with Professor Jeerson or his surname I forget at a minute, but he talked about he was doing research on exosomes. These are tiny vesicles secreted by stem cells that contain regenerative factors and they may offer stem cell benefits without needing full transplantation. And they are being studied for skinaging, neuro degeneration, and the heart disease. And I'm particularly interested in whether harnessing the part of these exosomes can be used without any of the complications, and other things that you could have a look at some peptides and other emerging therapies. So there's a peptide called epitalent. This is a peptide that's been shown to activate telomerias, extend lifespan, and enhance stem cell function in animals, and certainly there are people who are taking that peptide. Again, you will have access to peptides much easier in places like the United States than you will in the UK or Australia. But you can actually get these things in inverted commas for research purposes. And another peptide that shows promise is thymosin beta four that plays a role in tissue rappair, in stem cell mobilization, and especially in the cardiovascular system. And then there's something called g it's CaCu r copper peptide has been known for enhancing wound healing, skin regeneration, and stem cell activity again in animal studies. So to close look, there's a pretty complicated topic this one, but stem cells are a major driver of aging, both the and indirectly through some of those other mechanisms that we talked about earlier on. But research shows that lifestyle interventions, particularly exercise and some of the different fasting types and some of these also emerging therapies can definitely help protect and even rejuvenate our stem cells. So just key takeaway summary, exercise is very, very powerful. That should be your go to calorie restriction or fasting. Any of those different fasting protocols, particularly the more prolonged fasting protocols, definitely things that we can do to enhance our stem cell renewal long longevity. Then, for those who want to play more in the pharmaceuticals space or the molecule space, wrap amcin definitely kneeled on something that can have an effect, but we do need to see studies in humans before everybody goes and tries to get rap am and met forman again can impact on stem cells, but whether or not it directly improves aging is yet to be known. There is another study looking at met form and now which I think will give us a lot more detail. REDS virtul again shows a bit of promise in stem cells, but has no impact on aging in the interventions testing program, so it may have some effects, but I certainly wouldn't be going out and spending any money on res viatrol, but then definite stuff that has potential or proven potential actually stem cells therapies, the exosomes one I've really got my eye on, and some of those various peptides. So that's it for this week, folks. Hopefully that gives you a little bit of insight around stem cells and how rejuvenating could be one of the most effective ways to extend our health span. Stay tuned for episode eleven. Well, I'll go into the can last major hallmark of aging. Got you next time

Hey, everybody, welcome back to another edition of Wisdom Wednesdays and our series on the major hallmarks of aging, And today we are on number ten out of twelve and we're talking about stem cell exhaustion, one of the key drivers of aging that affects tissue regeneration, immune function, and overall vitality. So stem cells you've probably heard of, and they are cells that are essential for repairing and maintaining our tissues. But as we age, their ability to self renew and function declines. And they are two different things, that self renewal and their function, and together these two declines lead to weaker muscles, slower wound healing, immune dysfunction, and increased risk of diseases like osteoporosis and neurodegeneration, and lots of others. But here's the really interesting exciting part. Emerging research is showing that things like exercise, calorie restriction, targeted pharmaceuticals, and even stem cell based therapies can help combat stem cell exhaustion and potentially rejuvenate aging tissues. So let's explore that in a little bit more depth. So, overall stem cell exhaustion occurs to a combination of both intrinsic and extrinsic factors, which means stuff that's inside the body and outside the body. And the first is DNA damage accumulation. Now you're going to notice there are a number of the other hallmarks of aging that play into this, and that's just because the body is a complex ecosystem. So DNA damage accumulation, which is one of the hallmarks of aging in and of itself, but over time, exposure to oxidive stress, radiation and toxins leads to DNA mutations in stem cells right reducing their ability to divide and to regenerate tissues. And then next is telomere shortening because their cells right stem cells also have telemeres and limited division potential, and as their telomeres, remember those protective caps on the chromosomes, As those telomeres shorten, they lose their functionality. Then we have epigenetic changes, which again is another major hallmark of aging, but age related alterations in DNA methylation and histone modifications that we talked about in that episode. They empower stem cell identsity and renewal, and then chronic inflammation, which we have also discussed. The aging immune system secrets. Those pro inflammatory cider kinds that we talked about, and they can disrupt stem cell function and the surrounding niche. And then one that we haven't talked about yet. I'm leaving it to Alaska. It's my favorite, is mitochondrial dysfunction and aging stem cells generate more reactive oxygen species and that then damages the cellular components and accelerates stem cell exhaustion. So they are the major mechanisms by which it happens. Now let's talk about stuff that we can do. So exercise again, you'll be not surprised here. It's one of the most potent tools to maintain and rejuvenate stem cells. And if you think about it, exercise impacted all those other things we talked about, the DNA damage, telomeres, epigenetic changes, the inflammation, and the mitochondria you'll find out. So therefore it's going to play a role both directly and indirectly. So what exercise does, and particularly in muscle sales, it activates what's called satellite sales. These are muscle stem cells, and then enhances our muscle regeneration. Right, that makes sense if you're activating your muscles and from exercise, they are obviously going to look after themselves better. The next thing that exercise does is it promotes hematopoetic try saying that when you're pissed, hematopoetic stem cell function and that improves our immune and our blood cell production. Exercise also enhances neurogenesis the creative new brain cells. I've talked about that ad nauseum on the podcast, and that improves cognition and protects against neurodegenerative diseases. And then exercise also enhances our mitochondrial efficiency again we're going to do a full episode in this, and reduces oxidative stress, helping the stem cells to maintain their function. So evidence for this, there was a study the cell stem cell and find that endurance exercise increases the regenerative capacity of skeletal muscle stem cells by improving mitochondrial function and reducing inflammation. And research in Nature communication and there's a heap of other research around this shows that aerobic exercise and actually other research shows that strength training boosts BDNF, which enhances neural stem cells survival. So we know that bdn F actually peaks around lactate threshold and where you're producing lactic acid that is when we get a big spike and BDNF because lactate actually crosses the blood brain barrier and directly stimulates the production of BDNF, which enhances our neural stem cell survival. So engaging in that mix of resistance training and cardiovascular training, but making sure you're doing some of it high intensity is really really key. Second is about calorie restriction and the different types of fasting. So they have both been shown to extend lifespan in mice and other animals, but also improve stem cell function by reducing metabolic stress and inflammation. And high calorie restriction does it. And also some of the fasting protocols will will do this by enhancing autophogy so that triggers the cellular cleanup process. Remember autophogy is basically a spring clean for your cells and that removes damage proteins and damage mitochondria, helping stem cells to say functional. And the fasting protocols and calorie restriction also increase this stem cell pull and that's been shown in animals and that it prevents this stem cell depletion, particularly in the gut and the hemo hematopoetic system, and it also improves stem cell quiescence. So this quiescence is a kind of a dormant but healthy state, so not sinescence. Member we talked about those zone and it actually makes them more resilient and extends their lifespan. So studying cell metabolism found that short term fasting increased into style stem cell regeneration in aged mice by twofold. And we do have to be aware mice are not always well, they're not humans ever, but we don't see it always being replicated. But these sources of studies can only be done in nice but research in nature demonstrated that lifelong calorie restriction also did that in older animals. But intermittent fasting and the different protocols that we've talked about, there is some evidence that they may activate autoplogy, and particularly in muscle cells, and especially if you go out for a run or do some cardio in a fasted state, there's good evidence that that activates muscle cell autoplogy. But the prolonged fasting, you know, this is the seventy two hour plus that has been shown to trigger stem cell renewal, especially in the immune system, and there's quite a lot of evidence of that even in humans. So let's not talk about M tour inhibitors. Now, we have mentioned these in a previous podcast, but something that is on my radar, which I've talked about, is this M tour inhibitors because this M to our pathway, So M tour stands for mechanistic or mammalian some people say target of wrappamasin and it actually promotes selle growth. But with that metabolism and aging. Now, M tour activation is crucial for muscle growth and immune function, but it's this chronic overactivation that accelerates aging and actually accelerates sem stale depletion. Now, again I mentioned before, we have to be very careful to distinguish between M tour inside the muscle and M tour outside the muscle, because inside the muscle is good thing, but outside the muscle, after we've reached our food age can become problematic over the long run. So ones that are being studied now M toor inhibitors rapam iicin. I've talked about that. That's a very well known M tour inhibitor. It is extended lifespan in animal studies and rejuvenated aged heematopoetic stem cells and there are current trials investigating its potential for improving immune function and reducing age related diseases. And as I've said before, in the Interventions Testing Program, which is a massive program looking at all these particular agents that could extend lifespan done in animals obviously, and the one the big star is rapam iosin and it's been done in nice, it's currently being done in dogs, and if it shows the same protocol then there is good potential for rappamacin to act in humans. There's a lot of people excited about that in the scientific community. And the next one is met foreman. That's a diabetes struggle game. We've talked about this before, but it appears that it may be able to modulate m tour signaling and reduce inflammation, possibly protecting SEM cells, and studies show it improves muscle stem cell function in aging animals, but studies in human show that met forman can inhibit the benefits of exercise, so kind of watch this space. Res Virtual is a polyphenol that's found in red wine and it activates AMPK, which is a longevity pathway and indirectly inhibits SEM tour. Theoretically, supporting stem cell health. But I do want to say that Virtual was shown in the Interventions testing program to have no effect on aging. Whether it's having some effects on stem cells, maybe that's true, but overall in terms of aging, whereas Virtual is not an anti aging therapy, even though it's being promoted all over the internet as one of those. Let's now talk about some potential stuff for the future, which you know is being done in some places. But this is stem cell therapies. And if you live in Australia, good luck trying to get stem cell therapies. But certainly in the United States you can get some some of those commercially, and in places like Mexico and Panama and stuff like that, there's a lot of stem cell therapies going on, and probably some other countries around the world. And so there's different types of stem sale therapies, and I'm not going to go into a massive detail on them, but just as an overview, the first one would be messen chymo or mensynco, depending whether your British or American in terms of your pronunciation. That's missing chymeal sten cell therapy mses from bone marrow fat or umbilical cord have actually been shown to reduce inflammation, promote tissue repair, and improve immune function. And there's current clinical trials in humans testing and missing chymal stem cell therapies for osteoarthritis, neurodegenerative diseases, and immune regeneration. Then the next one is induce plury potent stem cells. So plury potent stem cells. These are cells that have the ability to turn into any cells, but scientists can now reprogram adult cells into stem cells, offering potential for regenerative treatments. And studies show that induced pluri protent stem cells could restore aged organ function, but there are risks like tumor formation that do need to be addressed. Then we have stem cell derived exosomes, so exosomes. Actually did a podcast with Professor Jeerson or his surname I forget at a minute, but he talked about he was doing research on exosomes. These are tiny vesicles secreted by stem cells that contain regenerative factors and they may offer stem cell benefits without needing full transplantation. And they are being studied for skinaging, neuro degeneration, and the heart disease. And I'm particularly interested in whether harnessing the part of these exosomes can be used without any of the complications, and other things that you could have a look at some peptides and other emerging therapies. So there's a peptide called epitalent. This is a peptide that's been shown to activate telomerias, extend lifespan, and enhance stem cell function in animals, and certainly there are people who are taking that peptide. Again, you will have access to peptides much easier in places like the United States than you will in the UK or Australia. But you can actually get these things in inverted commas for research purposes. And another peptide that shows promise is thymosin beta four that plays a role in tissue rappair, in stem cell mobilization, and especially in the cardiovascular system. And then there's something called g it's CaCu r copper peptide has been known for enhancing wound healing, skin regeneration, and stem cell activity again in animal studies. So to close look, there's a pretty complicated topic this one, but stem cells are a major driver of aging, both the and indirectly through some of those other mechanisms that we talked about earlier on. But research shows that lifestyle interventions, particularly exercise and some of the different fasting types and some of these also emerging therapies can definitely help protect and even rejuvenate our stem cells. So just key takeaway summary, exercise is very, very powerful. That should be your go to calorie restriction or fasting. Any of those different fasting protocols, particularly the more prolonged fasting protocols, definitely things that we can do to enhance our stem cell renewal long longevity. Then, for those who want to play more in the pharmaceuticals space or the molecule space, wrap amcin definitely kneeled on something that can have an effect, but we do need to see studies in humans before everybody goes and tries to get rap am and met forman again can impact on stem cells, but whether or not it directly improves aging is yet to be known. There is another study looking at met form and now which I think will give us a lot more detail. REDS virtul again shows a bit of promise in stem cells, but has no impact on aging in the interventions testing program, so it may have some effects, but I certainly wouldn't be going out and spending any money on res viatrol, but then definite stuff that has potential or proven potential actually stem cells therapies, the exosomes one I've really got my eye on, and some of those various peptides. So that's it for this week, folks. Hopefully that gives you a little bit of insight around stem cells and how rejuvenating could be one of the most effective ways to extend our health span. Stay tuned for episode eleven. Well, I'll go into the can last major hallmark of aging. Got you next time