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Wisdom Wednesdays - Anti-aging strategies part 6: Countering deregulated nutrient sensing · Hardiness with Dr Paul Taylor

• 0:09
  Speaker 1: Hey, everybody, Welcome to another edition of Wisdom Wednesdays, and
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  Speaker 1: we are continuing our series on anti aging. Are combating
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  Speaker 1: the major hallwarks of aging, and today is episode six,
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  Speaker 1: so we are halfway through and we're going to talk
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  Speaker 1: today about disregulated nutrient sensing. So, hi, metabolism and aging
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  Speaker 1: are connected, and disregulated nutrient sensing or deregulated what if
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  Speaker 1: you want to call it, that's one of the key
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  Speaker 1: drivers of aging. So in simple terms, to explain it,
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  Speaker 1: nutrient sensing refers to how our cells detect and respond
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  Speaker 1: to nutrients such as glucose, amino acids, and fats, and
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  Speaker 1: this process controls our energy balance, whether or not we're
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  Speaker 1: gaining or losing weight, but also cellular growth and our
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  Speaker 1: longevity as well. But as we age, we know that
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  Speaker 1: our ability to properly regulate nutrients sensing declines, as to
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  Speaker 1: do many metabolic processes, and that leads to increased metabolic
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  Speaker 1: issues such as insulin resistance, obesity, type two diabetes, Alzheimer's disease,
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  Speaker 1: and accelerated aging. Now, the good news is that, like
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  Speaker 1: the rest of these hallmarks, exercise, diet and targeted interventions
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  Speaker 1: can have an impact, and we know that they can
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  Speaker 1: restore nutrients sensing and help to slow aging at a
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  Speaker 1: cellular level. So let's dive in a little bit so ourselves,
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  Speaker 1: they rely on these key pathways to monitor and respond
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  Speaker 1: to nutrient levels. So think of them like biological fuel gauges.
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  Speaker 1: I think that's probably the best analogy. And they adjust
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  Speaker 1: metabolism based on our food availability. And there's four major
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  Speaker 1: pathways involved in nutrients sensing. So the first one is
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  Speaker 1: in sin and IGF one and that's a growth pathway,
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  Speaker 1: so inin and inchin like growth factor one, they regulate
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  Speaker 1: regulate sorry our glucose uptake and our cell growth. And
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  Speaker 1: when they're overactivated, these pathways contribute to aging and increased
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  Speaker 1: disease risks, particularly of diabetes and obesity. And then the
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  Speaker 1: second pathway is m tour mammalian target of rapamycin, and
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  Speaker 1: that's a growth and anabolism pathway, so it's a building pathway.
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  Speaker 1: So are now this m tour promotes protein synthesis and
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  Speaker 1: sell growth. Now, chronic overactivation of it due to excessive calories. Overall,
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  Speaker 1: being in a constant fed state is linked to obesity, cancer,
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  Speaker 1: and reduce longevity. But as I'll explain, later there's a
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  Speaker 1: lot of controversy in this topic. Then the third word
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  Speaker 1: pathway is AMPK and that's I think of this as
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  Speaker 1: a real energy sensor. So when our energy is low,
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  Speaker 1: if we've been fasting or exercising, AMPK activates fat burning
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  Speaker 1: and mitochondrial function, and also autophogy the cellular cleanup where
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  Speaker 1: it recycles lots of damage parts of the cell to
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  Speaker 1: actually recreate energy, which is very very clever. And we
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  Speaker 1: know that higher activity of AMPK is linked to longer
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  Speaker 1: lifespan and better metabolic health. And then the fourth pathway
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  Speaker 1: are cerituons, and these are often referred to as longevity regulators.
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  Speaker 1: And these certuons regulate our cell repair, our DNA stability,
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  Speaker 1: and mitochondrial function, and they're activated by and things such
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  Speaker 1: as fasting and calorie restriction. And then there's a lot
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  Speaker 1: of controversy about this. Certain plant compounds reds veratrol was
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  Speaker 1: touted as a real act the Vieta of turturns largely
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  Speaker 1: the work of David Sinclair, which has now been firmly debunked.
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  Speaker 1: So I'm going to come back to res virtual in
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  Speaker 1: a little bit, but we can see that there's still
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  Speaker 1: a lot that we don't know about these different pathways,
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  Speaker 1: and we know more about some than others. Now, when
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  Speaker 1: we're young, all of these systems working harmony. But when
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  Speaker 1: we eage, this nutrient sensing becomes dysregulated, leading to metabolic dysfunction.
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  Speaker 1: And so what happens is insulin resistant develops. We become
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  Speaker 1: less responsive to insulin, and that leads to chronically high
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  Speaker 1: blood sugar, increased diabetes risk, and dementia. You've heard me
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  Speaker 1: talk about dementia and particularly Alzheimer's diseases, type three diabetes
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  Speaker 1: and the other thing. M tour can become overactivated, and
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  Speaker 1: that can contribute to chronic inflammation, excessive cell growth, reduced
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  Speaker 1: a toophogy, and accelerated aging, and then this AMPK that declines,
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  Speaker 1: and when that is lower, your body tends to store
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  Speaker 1: more fat, it burns less energy, struggles with cellular repair,
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  Speaker 1: and you put on weigh and start to fall apart,
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  Speaker 1: and Thenswertwin's become suppressed. Particularly this is accentiated by poor
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  Speaker 1: that lacks of lack of exercise and excessive calorie intake,
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  Speaker 1: and that then impoers mitochondrial function and longevity. And the
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  Speaker 1: result of all of this, it's a higher risk of
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  Speaker 1: metabolic diseases, you get increased inflammation and faster biological aging.
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  Speaker 1: So let's now talk about the interventions. So again, first off,
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  Speaker 1: cab off the rank you'll not be surprised to hear
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  Speaker 1: is exercise. We know that exercise increases insulin sensitivity. There's
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  Speaker 1: oodles and oodles of research around that both aerobic slash,
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  Speaker 1: high intensity interval training and strength training, and all of
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  Speaker 1: them enhance glucose uptake and lower our blood sugar, make
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  Speaker 1: it more stable and reduce our diabetes risk and our
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  Speaker 1: risk of Altimer's disease. Exercise also activates a MPK pathway
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  Speaker 1: and that promotes fat metabolism, reducing inflammation and enhances our
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  Speaker 1: cellular cleanup. Exercise also balances M tour and this is
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  Speaker 1: the key thing. This M tour needs to be in balanced,
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  Speaker 1: this growth versus repair. And we know that that moderate
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  Speaker 1: to vigorous physical activity stimulate its M tour just enough
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  Speaker 1: to build muscle while allowing proper cellular repair. We know
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  Speaker 1: that overeating without exercise leads to constant M tour activation,
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  Speaker 1: increasing disease risk, and some researchers think there's a significant
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  Speaker 1: difference between M tour being activated within the muscle cells
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  Speaker 1: and M tour being activated outside of the muscle cells.
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  Speaker 1: So the M tour pathway certainly is not crystal clear.
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  Speaker 1: You know, some longevity components are proponents talk about that
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  Speaker 1: we should be doing fasting and long term calorie restriction,
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  Speaker 1: and that is probably not looking like it's the answer,
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  Speaker 1: particularly for primates and especially humans. And then the fourth
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  Speaker 1: way that exercise restores are the nutrients sensing. Is it
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  Speaker 1: boosts or tuns and these DNA repairer and longevity pathways
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  Speaker 1: and improves mitochondrial function and reduces eating markers. So other
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  Speaker 1: things that we can do is following a balanced diet
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  Speaker 1: and making sure we're not constantly in a FAED state.
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  Speaker 1: And so this is where I think we should be
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  Speaker 1: eating a diet, And it doesn't matter whether you're vegetarian, vegan, paleo,
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  Speaker 1: high fat, low carb, low fat, high carb, just reducing
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  Speaker 1: our amount of ultra processed foods, making sure that we're
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  Speaker 1: eating lots of real foods what I call low hi stuff,
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  Speaker 1: and making sure we're having lots of of fresh fruit
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  Speaker 1: and vegetables with have polyphenols and flavonoids that really help
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  Speaker 1: to support these cellular pathways. I think that's really key.
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  Speaker 1: And then making sure that we're not in a constantly
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  Speaker 1: fed state. I think this whole idea that we should
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  Speaker 1: have three meals a day plus snacks is really not
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  Speaker 1: helpful because it particularly impacts on M tour and switches
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  Speaker 1: M tour on all of the time. I think we're
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  Speaker 1: much better to have two, if you like, but certainly
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  Speaker 1: three good solid meals that have enough protein and fat,
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  Speaker 1: and then you won't need the snacks in between, and
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  Speaker 1: you won't constantly turn on that M tour pathway. So
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  Speaker 1: another promising mechanism to help with this is intermittent fasting
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  Speaker 1: or time restricted eating. So fasting naturally activates ampk and sertoons,
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  Speaker 1: and the thinking is certainly in mace and other animals
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  Speaker 1: that can reduce age will of the damage. There's still
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  Speaker 1: a little bit of debate about this with humans, but
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  Speaker 1: it would appear that periods of fasting, such as like
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  Speaker 1: a three or a five day water fast can really
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  Speaker 1: help with cellular cleanup. And then fifth sixteen to eight
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  Speaker 1: fasting or or you know, pressing your your eating into
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  Speaker 1: a ten hour window or a worst case, a twelve
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  Speaker 1: r window, or certainly an eight our window. That is
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  Speaker 1: a simple way to reset nutrient sensing. But I would
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  Speaker 1: say it really depends here whether or not you're doing
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  Speaker 1: you should be doing intermittent fasting really depends on your
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  Speaker 1: life stage and your metabolic health. So I would say
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  Speaker 1: that if your metabolic health is not great, then give
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  Speaker 1: intermittent fasting or time restricted feeding a crack. But if
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  Speaker 1: you're a bit older, certainly fifty plus, and you're in
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  Speaker 1: good metabolic health, right, you're pretty late. You've got no
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  Speaker 1: issue with your blood sugar or those sorts of things,
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  Speaker 1: and maybe doing constant time restricted feeding might not be
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  Speaker 1: useful because of its impact on muscle mass. So that
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  Speaker 1: still needs to be cleared up. So I'm one that
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  Speaker 1: kind of sits on the fence a little bit. I
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  Speaker 1: used to do sixteen eight. I stopped doing it because
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  Speaker 1: I was losing muscle quickly, But I've since realized that
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  Speaker 1: that was probably to do with my congenital heart issue,
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  Speaker 1: and that the bicos but aotic valve that I had
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  Speaker 1: causes you to lose weight and particularly muscle, So I
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  Speaker 1: might revisit this. But it is certainly not a close
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  Speaker 1: case about fasting whether or not it is beneficial for everybody.
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  Speaker 1: If you want to lose weight, time restricted eating can
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  Speaker 1: be very very effective, mostly because it reduces your calories.
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  Speaker 1: If you've got issues with your blood sugar, it can
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  Speaker 1: be really effective and it can help you with metabolic flexibility.
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  Speaker 1: And that's why I say you've got to look at
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  Speaker 1: what are your major health goals. Right. If you've got
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  Speaker 1: a reasonable amount of muscle, but you're not metabolically healthy,
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  Speaker 1: then maybe give it a crack. Then the next thing
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  Speaker 1: around nutrition is to make sure you're optimizing your protein intake.
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  Speaker 1: So again this is controversial around M tour. Some people
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  Speaker 1: say we don't want to overstimulate M tour, so we
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  Speaker 1: should have a low protein diet. I think that the
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  Speaker 1: evidence for that in humans and primates is really really weak.
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  Speaker 1: We know that one of the biggest issues for long
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  Speaker 1: term health is scarcopenia, that loss of muscle mass, and
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  Speaker 1: like I said earlier, M tour inside the muscle cells
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  Speaker 1: seems to be different than M tour outside of the
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  Speaker 1: muscle cells. So, especially as you get older, we want
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  Speaker 1: to be having one point six to two grams of
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  Speaker 1: protein per kilogram of body weight. Now, if you're significantly overweight,
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  Speaker 1: you would look at your target weight, and you would
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  Speaker 1: do that that calculation the old recommended daily intakes. In
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  Speaker 1: fact they're still there is zero point eight grams per kilogram.
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  Speaker 1: There are many many researchers, myself included, who think that
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  Speaker 1: that is way too low. It was based on old
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  Speaker 1: nitrogen balanced studies and it was never meant to be optimal.
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  Speaker 1: It was meant to be the amount to prevent disease.
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  Speaker 1: And we think now that that is definitely too low.
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  Speaker 1: So one point six to two grams spread over those
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  Speaker 1: three meals will make sure that you're getting enough protein,
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  Speaker 1: stimulating your muscle, and making sure you're not having lots
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  Speaker 1: of snacks so that you're not switching on m tour
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  Speaker 1: all of the time. Then when we get into the
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  Speaker 1: idea of supplements again a bit of controversy here. Now,
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  Speaker 1: Berberine is one that I would give a big tick.
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  Speaker 1: It has been shown to activate AMPK and improves insulin sensitivity.
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  Speaker 1: It can help people who have diabetes, and that's a
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  Speaker 1: natural supparant called berbermine. Berberine. Sorry, res veratrol, there was
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  Speaker 1: a lot a lot of stuff around res viatrol. It
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  Speaker 1: has been well and truly debunked that it's been shown
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  Speaker 1: that it does not activate surtoons, it does not increase lifespan.
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  Speaker 1: It's been tested in the Interventions Testing program, it's been debunked,
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  Speaker 1: and Professor David Sinclair has been called a charlatan by
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  Speaker 1: his Harvard colleagues. So if you're spending your money on
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  Speaker 1: res viatrol, I would suggest that you spend it elsewhere.
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  Speaker 1: And met Foreman is another one that showed a lot
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  Speaker 1: of promise because there was an early study showing that
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  Speaker 1: people who had diabetes who were taking met foreman actually
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  Speaker 1: outlived people who did not have diabetes and were not
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  Speaker 1: taken met forman. But since then and that created this
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  Speaker 1: whole stuff in the longevity space, and there was all
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  Speaker 1: these people taking met forman. We know that met forman
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  Speaker 1: interferes with exercise, and another study then came out and
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  Speaker 1: showed that actually people on diabetes who had met forman
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  Speaker 1: didn't live any longer. And when they went and reanalyzed
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  Speaker 1: the data from the first paper, it showed that there
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  Speaker 1: were a lot of methodo logical issues. So met forman
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  Speaker 1: is one that's kind of a yeah nah, But it
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  Speaker 1: is being tested in longevity research, so we may see
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  Speaker 1: that there are some benefits and one thing that has
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  Speaker 1: been consistently shown to extend lifespan, and this is just
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  Speaker 1: in MAE, but this is through the Interventions Testing program,
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  Speaker 1: which is the most rigorous assessments of molecules that could
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  Speaker 1: potentially extend lifespan is rapamycin and that has been shown
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  Speaker 1: over and over again to consistently extend lifespan in mice,
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  Speaker 1: and it appears to do so through its impact on
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  Speaker 1: m tour amongst other things. It is now being tested
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  Speaker 1: on dogs and if that shows promise on dogs, then
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  Speaker 1: I think people will really start to get excited. And
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  Speaker 1: I know there's a lot of people who take rap
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  Speaker 1: of mice in off label as a longevity drug. If
• 15:25
  Speaker 1: you live in Australia, you get no chance of getting it.
• 15:27
  Speaker 1: If you live in the States, you can probably get
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  Speaker 1: it from a doctor off label. So in closing this,
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  Speaker 1: disregulated or deregulated nutrient sensing is a major driver of
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  Speaker 1: aging and disease, but it is also highly controllable and
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  Speaker 1: through exercise, intermittent fasting, eating a whole food, low heat
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  Speaker 1: side diet, and potentially some targeted supplements, and by doing
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  Speaker 1: that we can restore our metabolic balance, we can improve
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  Speaker 1: our longevity and reduce our disease risk. So that's it
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  Speaker 1: for this week, folks. I'll catch you next time for
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  Speaker 1: episode seven.