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Wisdom Wednesdays - Anti-aging strategies part 11: Restoring our cellular clean-up processes (macroautophagy) · Hardiness with Dr Paul Taylor

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  Speaker 1: Hey, everyone, welcome to another edition of Wisdom Wednesdays, and
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  Speaker 1: welcome back to our ongoing journey which is almost complete
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  Speaker 1: about the hallmarks of aging. So today we're doing eleven
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  Speaker 1: out of twelve and we're going to talk about macro
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  Speaker 1: autophogy commonly just referred to as autophogy. That is a
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  Speaker 1: cellular process that is fundamental to staying biologically young, yet
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  Speaker 1: it often gets overlooked in aging discussions. And autophogy literally
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  Speaker 1: means self eating, but in the best possible way, and
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  Speaker 1: it's basically an internal clean up mechanism by which our
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  Speaker 1: sales break down and recycle damage proteins and dysfunctional organelles.
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  Speaker 1: They're like bits bits of the sale, such as mitochon
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  Speaker 1: and other accumulated metabolic junk. And when this system starts
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  Speaker 1: to break down, as it does when we age, the
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  Speaker 1: consequences show up virtually in every organ system in the body.
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  Speaker 1: So let's explore it in a little bit more depth. Basically,
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  Speaker 1: autoplogy is a cellular housekeeping process, and it's the mechanism
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  Speaker 1: by which cells degrade and recycle internal components, helping to
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  Speaker 1: maintain balance and resilience within cells and specifically in macroautoplogy.
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  Speaker 2: Parts of the cell.
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  Speaker 1: As I said earlier, like damage mitochondria, are aggregated proteins.
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  Speaker 2: What happens is they get wrapped.
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  Speaker 1: In a membrane to form this compound called an autophagisome,
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  Speaker 1: and that then infuses with something called a lysisome, and
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  Speaker 1: the contents then are either.
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  Speaker 2: Broken down or reuse used and removed.
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  Speaker 1: And it's basically our body's way of doing recycling. And
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  Speaker 1: it's very very clever because what it does is it
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  Speaker 1: actually keeps the energy going in the cell and the
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  Speaker 1: process is tightly regulated by nutrient sensing pathways like m
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  Speaker 1: tour which we've talked about before, and MPK or amp
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  Speaker 1: kiness and when energy is low or our cells are
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  Speaker 1: under stress, MPK is activated and that inhibits m tour,
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  Speaker 1: therefore inducing autopogy. So, if you can remember from previous podcasts,
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  Speaker 1: m tor stimulates growth, AMPK stops that growth and activates
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  Speaker 1: this autoplogy, and it's basically a way that we can
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  Speaker 1: survive at a cellular level in times of low energy
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  Speaker 1: or low stress. And it's a big deal because it
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  Speaker 1: really is essential for us responding to stress, detoxifying the
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  Speaker 1: cell and even defending against pathogens. And it is really
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  Speaker 1: key for protecting our brain, for muscle maintenance, for immune
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  Speaker 1: system regulation, and for metabolic balance.
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  Speaker 2: So it's widespread throughout the body.
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  Speaker 1: And when it declines with age, it is associated with
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  Speaker 1: a protein build up, and that in the brain contributes
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  Speaker 1: to Alzheimer's and Parkinson's. You'd have heard me talk about
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  Speaker 1: TAUL proteins in the brain. It also contributes to immune
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  Speaker 1: dysfunction when it goes wrong, Waker stress responses reduced the
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  Speaker 1: ability to remove defective mictochondria and then accelerated organ degeneration.
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  Speaker 1: So you can see there's a number of mechanisms by
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  Speaker 1: which it contributes to accelerated aging, and as well as
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  Speaker 1: affecting neurodegeneration and immune agen it also contributes to liver
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  Speaker 1: dysfunction because partasites rely heavily on a hoopogy to manage
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  Speaker 1: what's called lipid overload. And it also contributes to muscle
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  Speaker 1: loss because damage proteins and mitochondria build up in muscle cells,
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  Speaker 1: empowering muscle regeneration. And basically, just think of it like
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  Speaker 1: the janitor of your body, and when the janitor goes
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  Speaker 1: on strike, the whole building aka, your body starts to suffer.
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  Speaker 2: So let's talk.
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  Speaker 1: About ways that we can boost autopogy science backed ways.
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  Speaker 1: The first one no prices for guessing is exercise. It
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  Speaker 1: is a natural autopogy enhancer. When we exercise sells sense
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  Speaker 1: this energy stress because at PAI drops when we're exercising,
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  Speaker 1: and then amp rises and that activates amp kind is
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  Speaker 1: leading to mpt or inhibition and autopogy induction. And so
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  Speaker 1: basically the key mechanisms are as I said, the AMPK
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  Speaker 1: activiation and inhibiting m tour but then reactive oxygen species production
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  Speaker 1: that actually signals us to do a cellular cleanup. And
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  Speaker 1: then mild kinds, which I've talked about before. These magical
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  Speaker 1: molecules released from muscle. They have systemic anti inflammatory effects.
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  Speaker 1: So there's a really complicated process that actually goes on.
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  Speaker 1: And in studies of older mice, exercise actually restored autophagic
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  Speaker 1: fluss in sorry autophagic flux in muscles, improving strength and regeneration.
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  Speaker 1: And in the brains of the mice it boosted clearance
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  Speaker 1: of dysfunctional mitochondria and synaptic proteins, which is key for
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  Speaker 1: cognitive health. The next thing is fasting and calorie restriction,
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  Speaker 1: and that kind of acts as a master switch for autopogy.
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  Speaker 2: Fasting.
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  Speaker 1: Prolonged fasting is one of the most potent natural ways
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  Speaker 1: to activate autopogy and the energy deficit active. It's AMPK,
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  Speaker 1: suppresses m tour and boost suritans and they all drive autophogy.
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  Speaker 1: And then the key benefits of that is increased lifespan
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  Speaker 1: in model organisms, protection against neurodegeneration, enhanced intestinal and hemopoetic
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  Speaker 1: stem cell function, which we talked about last time, and
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  Speaker 1: short term fasting of twenty four to forty eight hours
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  Speaker 1: has actually been shown to double stem cell activity in
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  Speaker 1: the gut and immune system via autoplogy pathways. And then
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  Speaker 1: if you do a more prolonged fast of three four
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  Speaker 1: days or more, that enhances mitophagi and that's the clearing
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  Speaker 1: of damage mitochondria. It also improves metabolic flexibility and has
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  Speaker 1: rejuvenating effects on the immune system. Quite a lot of
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  Speaker 1: studies have now shown that this happens in both animals
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  Speaker 1: and in humans. The third way actually just on the
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  Speaker 1: fasting thing. If you exercise in the fasted state, it
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  Speaker 1: also enhances autopogy within muscle cells. Only within muscle cells,
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  Speaker 1: and that's just like an overnight fast and then going
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  Speaker 1: and doing some morning exercise, so that can be really
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  Speaker 1: useful for our muscles. And then the third way, which
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  Speaker 1: is kind of linked to fasting a little bit, is
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  Speaker 1: ketones and they actually fuel clean up and resilience inside
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  Speaker 1: our cells. So when we are fasting or on a
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  Speaker 1: low carb diet, our body produces ketone bodies such as
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  Speaker 1: beta hydroxy puryate, and they act as a signaling molecule
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  Speaker 1: for longevity. And we know just if you take beta
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  Speaker 1: hydroxy purury it that inhibits what we call his stone deacylases.
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  Speaker 1: This is a bit of a mouthful podcast, isn't it,
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  Speaker 1: But when you inhibit those things, it actually increases our topogy,
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  Speaker 1: gene expression and beta hydroxy butty. It also suppresses inflammation
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  Speaker 1: and oxidative stress and enhances and over of our mitochondria,
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  Speaker 1: keeping them healthy. And studies show that ke tonges actually
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  Speaker 1: mimic calorie restriction and provide neuroprotective effects via enhancement of autopogy.
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  Speaker 1: And there's now research going on that maybe you don't
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  Speaker 1: have to fast, you can actually take supplemental key tones
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  Speaker 1: and get some of these benefits. So let's talk about
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  Speaker 1: stuff that's on the horizon or that's being tested or
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  Speaker 1: proven right now around autopogy. One you'll not be surprised
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  Speaker 1: to hear if you've listened to previous podcast is rapamiacin
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  Speaker 1: that inhibits m tour C one and that's one of
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  Speaker 1: the central pathways for suppressing autoplogy because it's.
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  Speaker 2: A growth pathway.
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  Speaker 1: Rapimiasin extends lifespan in mice. It's now being studied in dogs.
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  Speaker 1: Matt Chamberlin is doing a big study on that seeing
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  Speaker 1: if it can enhance the lifespan of dogs, and I
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  Speaker 1: think that study is due to be released in the
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  Speaker 1: next year or so. And it's also being tested rapamasin
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  Speaker 1: in humans for immune system regeneration or rejuvenation and also
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  Speaker 1: Alzheimer's and forcycopedia that loss of bone and muscle. And
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  Speaker 1: we'll just see what happens when those studies are published.
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  Speaker 1: Then the next one is spermidine.
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  Speaker 2: So this is a a polyamine if you really interested.
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  Speaker 1: It's found in wheat, germ soy, and age cheese like
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  Speaker 1: blue cheese, and it's been shown to boost autophogy and
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  Speaker 1: actually has cardiovascar and cognitive benefits and animal studies.
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  Speaker 2: You can buy that as a supplement.
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  Speaker 1: And then there's resveratrol that's found in red wine. There's
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  Speaker 1: debit about whether it activates surtins, but it does seem
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  Speaker 1: to mimic some fasting effects and possibly can enhance mitochondria,
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  Speaker 1: biogenesis and autophogy. But like I said in previous podcasts,
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  Speaker 1: it has been proven that it actually doesn't extend lifespan.
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  Speaker 1: Other things that are being studied at met Foreman, and
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  Speaker 1: that's a diabetes drug that some people think has longevity potential.
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  Speaker 1: It's been shown to activate amp kinds and improve metabolic health,
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  Speaker 1: and people think that it indirectly supports autoplogy. So watch
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  Speaker 1: this space on met Foreman. And then there's a couple
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  Speaker 1: of other molecules that are being tested. One is Trehallows
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  Speaker 1: that's a kind of a sugar molecule that induces autoplogy
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  Speaker 1: independent of the m to our pathway. And then something
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  Speaker 1: called another mouthful to finish the podcast, peptides like FOXO
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  Speaker 1: four d RII. Who the hell comes up with these names?
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  Speaker 1: This is an experimental agent that induces selective autoplogy in
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  Speaker 1: these sinescent or zombie sales.
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  Speaker 2: So in closing.
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  Speaker 1: Firstly, I promise that next week's the last one mould
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  Speaker 1: have so many big words. But closing thoughts is that
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  Speaker 1: when this macrotophagy becomes disabled or doesn't work well, it's
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  Speaker 1: like a broken recycling plant inside yourselves and without it,
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  Speaker 1: damage starts to pile up, leading to dysfunction, disease, and
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  Speaker 1: faster aging. But the good news is that you can
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  Speaker 1: induce ortophogy naturally through exercise, prolonged fasting, and perhaps a
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  Speaker 1: kidogenic diet or ketone supplements, And there are some pharmological
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  Speaker 1: tools that are being tested that seem to have quite
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  Speaker 1: a bit of promise.
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  Speaker 2: And with most of the aging.
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  Speaker 1: Intervention, the best strategy is combining lifestyle and science backed
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  Speaker 1: tools to actually protect against this decline. So that's it
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  Speaker 1: for this week. In the next week session, the last one,
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  Speaker 1: it's going to be my favorite, we're going to talk
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  Speaker 1: about mitochondrial dysfunction. But until then, you're going to amuse
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  Speaker 1: yourself by re listening to this podcast to see if
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  Speaker 1: you can work out what the hell I said.
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  Speaker 2: Catch you next time,