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Speaker 1: Hey, everybody, welcome back to another edition of Wisdom Wednesdays

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Speaker 1: and our series on the major hallmarks of aging, And

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Speaker 1: today we are on number ten out of twelve and

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Speaker 1: we're talking about stem cell exhaustion, one of the key

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Speaker 1: drivers of aging that affects tissue regeneration, immune function, and

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Speaker 1: overall vitality. So stem cells you've probably heard of, and

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Speaker 1: they are cells that are essential for repairing and maintaining

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Speaker 1: our tissues. But as we age, their ability to self

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Speaker 1: renew and function declines. And they are two different things,

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Speaker 1: that self renewal and their function, and together these two

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Speaker 1: declines lead to weaker muscles, slower wound healing, immune dysfunction,

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Speaker 1: and increased risk of diseases like osteoporosis and neurodegeneration, and

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Speaker 1: lots of others. But here's the really interesting exciting part.

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Speaker 1: Emerging research is showing that things like exercise, calorie restriction,

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Speaker 1: targeted pharmaceuticals, and even stem cell based therapies can help

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Speaker 1: combat stem cell exhaustion and potentially rejuvenate aging tissues. So

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Speaker 1: let's explore that in a little bit more depth. So,

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Speaker 1: overall stem cell exhaustion occurs to a combination of both

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Speaker 1: intrinsic and extrinsic factors, which means stuff that's inside the

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Speaker 1: body and outside the body. And the first is DNA

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Speaker 1: damage accumulation. Now you're going to notice there are a

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Speaker 1: number of the other hallmarks of aging that play into this,

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Speaker 1: and that's just because the body is a complex ecosystem.

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Speaker 1: So DNA damage accumulation, which is one of the hallmarks

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Speaker 1: of aging in and of itself, but over time, exposure

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Speaker 1: to oxidive stress, radiation and toxins leads to DNA mutations

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Speaker 1: in stem cells right reducing their ability to divide and

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Speaker 1: to regenerate tissues. And then next is telomere shortening because

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Speaker 1: their cells right stem cells also have telemeres and limited

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Speaker 1: division potential, and as their telomeres, remember those protective caps

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Speaker 1: on the chromosomes, As those telomeres shorten, they lose their functionality.

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Speaker 1: Then we have epigenetic changes, which again is another major

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Speaker 1: hallmark of aging, but age related alterations in DNA methylation

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Speaker 1: and histone modifications that we talked about in that episode.

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Speaker 1: They empower stem cell identsity and renewal, and then chronic inflammation,

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Speaker 1: which we have also discussed. The aging immune system secrets.

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Speaker 1: Those pro inflammatory cider kinds that we talked about, and

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Speaker 1: they can disrupt stem cell function and the surrounding niche.

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Speaker 1: And then one that we haven't talked about yet. I'm

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Speaker 1: leaving it to Alaska. It's my favorite, is mitochondrial dysfunction

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Speaker 1: and aging stem cells generate more reactive oxygen species and

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Speaker 1: that then damages the cellular components and accelerates stem cell exhaustion.

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Speaker 1: So they are the major mechanisms by which it happens.

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Speaker 1: Now let's talk about stuff that we can do. So

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Speaker 1: exercise again, you'll be not surprised here. It's one of

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Speaker 1: the most potent tools to maintain and rejuvenate stem cells.

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Speaker 1: And if you think about it, exercise impacted all those

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Speaker 1: other things we talked about, the DNA damage, telomeres, epigenetic changes,

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Speaker 1: the inflammation, and the mitochondria you'll find out. So therefore

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Speaker 1: it's going to play a role both directly and indirectly.

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Speaker 1: So what exercise does, and particularly in muscle sales, it

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Speaker 1: activates what's called satellite sales. These are muscle stem cells,

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Speaker 1: and then enhances our muscle regeneration. Right, that makes sense

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Speaker 1: if you're activating your muscles and from exercise, they are

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Speaker 1: obviously going to look after themselves better. The next thing

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Speaker 1: that exercise does is it promotes hematopoetic try saying that

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Speaker 1: when you're pissed, hematopoetic stem cell function and that improves

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Speaker 1: our immune and our blood cell production. Exercise also enhances

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Speaker 1: neurogenesis the creative new brain cells. I've talked about that

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Speaker 1: ad nauseum on the podcast, and that improves cognition and

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Speaker 1: protects against neurodegenerative diseases. And then exercise also enhances our

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Speaker 1: mitochondrial efficiency again we're going to do a full episode

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Speaker 1: in this, and reduces oxidative stress, helping the stem cells

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Speaker 1: to maintain their function. So evidence for this, there was

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Speaker 1: a study the cell stem cell and find that endurance

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Speaker 1: exercise increases the regenerative capacity of skeletal muscle stem cells

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Speaker 1: by improving mitochondrial function and reducing inflammation. And research in

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Speaker 1: Nature communication and there's a heap of other research around

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Speaker 1: this shows that aerobic exercise and actually other research shows

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Speaker 1: that strength training boosts BDNF, which enhances neural stem cells survival.

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Speaker 1: So we know that bdn F actually peaks around lactate

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Speaker 1: threshold and where you're producing lactic acid that is when

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Speaker 1: we get a big spike and BDNF because lactate actually

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Speaker 1: crosses the blood brain barrier and directly stimulates the production

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Speaker 1: of BDNF, which enhances our neural stem cell survival. So

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Speaker 1: engaging in that mix of resistance training and cardiovascular training,

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Speaker 1: but making sure you're doing some of it high intensity

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Speaker 1: is really really key. Second is about calorie restriction and

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Speaker 1: the different types of fasting. So they have both been

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Speaker 1: shown to extend lifespan in mice and other animals, but

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Speaker 1: also improve stem cell function by reducing metabolic stress and inflammation.

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Speaker 1: And high calorie restriction does it. And also some of

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Speaker 1: the fasting protocols will will do this by enhancing autophogy

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Speaker 1: so that triggers the cellular cleanup process. Remember autophogy is

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Speaker 1: basically a spring clean for your cells and that removes

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Speaker 1: damage proteins and damage mitochondria, helping stem cells to say functional.

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Speaker 1: And the fasting protocols and calorie restriction also increase this

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Speaker 1: stem cell pull and that's been shown in animals and

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Speaker 1: that it prevents this stem cell depletion, particularly in the

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Speaker 1: gut and the hemo hematopoetic system, and it also improves

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Speaker 1: stem cell quiescence. So this quiescence is a kind of

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Speaker 1: a dormant but healthy state, so not sinescence. Member we

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Speaker 1: talked about those zone and it actually makes them more

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Speaker 1: resilient and extends their lifespan. So studying cell metabolism found

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Speaker 1: that short term fasting increased into style stem cell regeneration

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Speaker 1: in aged mice by twofold. And we do have to

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Speaker 1: be aware mice are not always well, they're not humans ever,

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Speaker 1: but we don't see it always being replicated. But these

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Speaker 1: sources of studies can only be done in nice but

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Speaker 1: research in nature demonstrated that lifelong calorie restriction also did

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Speaker 1: that in older animals. But intermittent fasting and the different

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Speaker 1: protocols that we've talked about, there is some evidence that

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Speaker 1: they may activate autoplogy, and particularly in muscle cells, and

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Speaker 1: especially if you go out for a run or do

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Speaker 1: some cardio in a fasted state, there's good evidence that

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Speaker 1: that activates muscle cell autoplogy. But the prolonged fasting, you know,

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Speaker 1: this is the seventy two hour plus that has been

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Speaker 1: shown to trigger stem cell renewal, especially in the immune system,

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Speaker 1: and there's quite a lot of evidence of that even

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Speaker 1: in humans. So let's not talk about M tour inhibitors. Now,

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Speaker 1: we have mentioned these in a previous podcast, but something

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Speaker 1: that is on my radar, which I've talked about, is

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Speaker 1: this M tour inhibitors because this M to our pathway,

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Speaker 1: So M tour stands for mechanistic or mammalian some people

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Speaker 1: say target of wrappamasin and it actually promotes selle growth.

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Speaker 1: But with that metabolism and aging. Now, M tour activation

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Speaker 1: is crucial for muscle growth and immune function, but it's

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Speaker 1: this chronic overactivation that accelerates aging and actually accelerates sem

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Speaker 1: stale depletion. Now, again I mentioned before, we have to

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Speaker 1: be very careful to distinguish between M tour inside the

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Speaker 1: muscle and M tour outside the muscle, because inside the

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Speaker 1: muscle is good thing, but outside the muscle, after we've

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Speaker 1: reached our food age can become problematic over the long run.

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Speaker 1: So ones that are being studied now M toor inhibitors

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Speaker 1: rapam iicin. I've talked about that. That's a very well

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Speaker 1: known M tour inhibitor. It is extended lifespan in animal

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Speaker 1: studies and rejuvenated aged heematopoetic stem cells and there are

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Speaker 1: current trials investigating its potential for improving immune function and

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Speaker 1: reducing age related diseases. And as I've said before, in

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Speaker 1: the Interventions Testing Program, which is a massive program looking

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Speaker 1: at all these particular agents that could extend lifespan done

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Speaker 1: in animals obviously, and the one the big star is

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Speaker 1: rapam iosin and it's been done in nice, it's currently

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Speaker 1: being done in dogs, and if it shows the same

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Speaker 1: protocol then there is good potential for rappamacin to act

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Speaker 1: in humans. There's a lot of people excited about that

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Speaker 1: in the scientific community. And the next one is met foreman.

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Speaker 1: That's a diabetes struggle game. We've talked about this before,

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Speaker 1: but it appears that it may be able to modulate

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Speaker 1: m tour signaling and reduce inflammation, possibly protecting SEM cells,

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Speaker 1: and studies show it improves muscle stem cell function in

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Speaker 1: aging animals, but studies in human show that met forman

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Speaker 1: can inhibit the benefits of exercise, so kind of watch

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Speaker 1: this space. Res Virtual is a polyphenol that's found in

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Speaker 1: red wine and it activates AMPK, which is a longevity

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Speaker 1: pathway and indirectly inhibits SEM tour. Theoretically, supporting stem cell health.

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Speaker 1: But I do want to say that Virtual was shown

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Speaker 1: in the Interventions testing program to have no effect on aging.

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Speaker 1: Whether it's having some effects on stem cells, maybe that's true,

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Speaker 1: but overall in terms of aging, whereas Virtual is not

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Speaker 1: an anti aging therapy, even though it's being promoted all

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Speaker 1: over the internet as one of those. Let's now talk

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Speaker 1: about some potential stuff for the future, which you know

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Speaker 1: is being done in some places. But this is stem

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Speaker 1: cell therapies. And if you live in Australia, good luck

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Speaker 1: trying to get stem cell therapies. But certainly in the

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Speaker 1: United States you can get some some of those commercially,

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Speaker 1: and in places like Mexico and Panama and stuff like that,

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Speaker 1: there's a lot of stem cell therapies going on, and

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Speaker 1: probably some other countries around the world. And so there's

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Speaker 1: different types of stem sale therapies, and I'm not going

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Speaker 1: to go into a massive detail on them, but just

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Speaker 1: as an overview, the first one would be messen chymo

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Speaker 1: or mensynco, depending whether your British or American in terms

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Speaker 1: of your pronunciation. That's missing chymeal sten cell therapy mses

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Speaker 1: from bone marrow fat or umbilical cord have actually been

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Speaker 1: shown to reduce inflammation, promote tissue repair, and improve immune function.

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Speaker 1: And there's current clinical trials in humans testing and missing

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Speaker 1: chymal stem cell therapies for osteoarthritis, neurodegenerative diseases, and immune regeneration.

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Speaker 1: Then the next one is induce plury potent stem cells.

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Speaker 1: So plury potent stem cells. These are cells that have

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Speaker 1: the ability to turn into any cells, but scientists can

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Speaker 1: now reprogram adult cells into stem cells, offering potential for

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Speaker 1: regenerative treatments. And studies show that induced pluri protent stem

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Speaker 1: cells could restore aged organ function, but there are risks

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Speaker 1: like tumor formation that do need to be addressed. Then

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Speaker 1: we have stem cell derived exosomes, so exosomes. Actually did

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Speaker 1: a podcast with Professor Jeerson or his surname I forget

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Speaker 1: at a minute, but he talked about he was doing

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Speaker 1: research on exosomes. These are tiny vesicles secreted by stem

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Speaker 1: cells that contain regenerative factors and they may offer stem

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Speaker 1: cell benefits without needing full transplantation. And they are being

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Speaker 1: studied for skinaging, neuro degeneration, and the heart disease. And

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Speaker 1: I'm particularly interested in whether harnessing the part of these

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Speaker 1: exosomes can be used without any of the complications, and

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Speaker 1: other things that you could have a look at some

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Speaker 1: peptides and other emerging therapies. So there's a peptide called epitalent.

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Speaker 1: This is a peptide that's been shown to activate telomerias,

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Speaker 1: extend lifespan, and enhance stem cell function in animals, and

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Speaker 1: certainly there are people who are taking that peptide. Again,

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Speaker 1: you will have access to peptides much easier in places

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Speaker 1: like the United States than you will in the UK

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Speaker 1: or Australia. But you can actually get these things in

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Speaker 1: inverted commas for research purposes. And another peptide that shows

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Speaker 1: promise is thymosin beta four that plays a role in

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Speaker 1: tissue rappair, in stem cell mobilization, and especially in the

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Speaker 1: cardiovascular system. And then there's something called g it's CaCu

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Speaker 1: r copper peptide has been known for enhancing wound healing,

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Speaker 1: skin regeneration, and stem cell activity again in animal studies.

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Speaker 1: So to close look, there's a pretty complicated topic this one,

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Speaker 1: but stem cells are a major driver of aging, both

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Speaker 1: the and indirectly through some of those other mechanisms that

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Speaker 1: we talked about earlier on. But research shows that lifestyle interventions,

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Speaker 1: particularly exercise and some of the different fasting types and

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Speaker 1: some of these also emerging therapies can definitely help protect

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Speaker 1: and even rejuvenate our stem cells. So just key takeaway summary,

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Speaker 1: exercise is very, very powerful. That should be your go

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Speaker 1: to calorie restriction or fasting. Any of those different fasting protocols,

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Speaker 1: particularly the more prolonged fasting protocols, definitely things that we

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Speaker 1: can do to enhance our stem cell renewal long longevity. Then,

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Speaker 1: for those who want to play more in the pharmaceuticals

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Speaker 1: space or the molecule space, wrap amcin definitely kneeled on

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Speaker 1: something that can have an effect, but we do need

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Speaker 1: to see studies in humans before everybody goes and tries

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Speaker 1: to get rap am and met forman again can impact

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Speaker 1: on stem cells, but whether or not it directly improves

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Speaker 1: aging is yet to be known. There is another study

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Speaker 1: looking at met form and now which I think will

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Speaker 1: give us a lot more detail. REDS virtul again shows

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Speaker 1: a bit of promise in stem cells, but has no

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Speaker 1: impact on aging in the interventions testing program, so it

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Speaker 1: may have some effects, but I certainly wouldn't be going

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Speaker 1: out and spending any money on res viatrol, but then

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Speaker 1: definite stuff that has potential or proven potential actually stem

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Speaker 1: cells therapies, the exosomes one I've really got my eye on,

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Speaker 1: and some of those various peptides. So that's it for

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Speaker 1: this week, folks. Hopefully that gives you a little bit

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Speaker 1: of insight around stem cells and how rejuvenating could be

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Speaker 1: one of the most effective ways to extend our health span.

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Speaker 1: Stay tuned for episode eleven. Well, I'll go into the

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Speaker 1: can last major hallmark of aging. Got you next time