1 00:00:09,400 --> 00:00:13,320 Speaker 1: Hey, everybody, welcome to another edition of Wisdom Wednesdays. Today, 2 00:00:13,360 --> 00:00:16,079 Speaker 1: we're going to talk about something that I find pretty 3 00:00:16,120 --> 00:00:19,520 Speaker 1: bloody fascinating and I reckon you've never heard of it, 4 00:00:19,600 --> 00:00:22,280 Speaker 1: are the vast majority of you. It is a type 5 00:00:22,320 --> 00:00:26,560 Speaker 1: of protein called clotho. Now you may not have heard 6 00:00:26,720 --> 00:00:30,520 Speaker 1: much about this protein and the associated gene, but it 7 00:00:30,640 --> 00:00:33,320 Speaker 1: turns out that recent research has shown that it plays 8 00:00:33,320 --> 00:00:37,080 Speaker 1: a major role in how we age and how well 9 00:00:37,159 --> 00:00:41,240 Speaker 1: are brain functions, and much more. Some people have got 10 00:00:41,360 --> 00:00:46,800 Speaker 1: genetic variants that give them more CLOTHO naturally, which research 11 00:00:46,880 --> 00:00:50,960 Speaker 1: is showing may well enhance their longevity and certainly seems 12 00:00:51,000 --> 00:00:55,800 Speaker 1: to protect against neurodegenerative diseases, which is why CLOTHO is 13 00:00:55,840 --> 00:00:59,920 Speaker 1: now being called the longevity gene. But it turns out, 14 00:01:00,280 --> 00:01:02,280 Speaker 1: and you got to wait till the end for this one, 15 00:01:02,640 --> 00:01:07,200 Speaker 1: that everybody can boost their cloth O levels naturally. Now, 16 00:01:07,240 --> 00:01:10,000 Speaker 1: before we get into all of that, let's talk about 17 00:01:10,000 --> 00:01:13,600 Speaker 1: what it is. So. Clotho was first discovered in nineteen 18 00:01:13,720 --> 00:01:17,679 Speaker 1: ninety seven. Unlike many great scientific discoveries, it was kind 19 00:01:17,720 --> 00:01:23,640 Speaker 1: of an accident. So a researcher called Makoto kore Kuroo. 20 00:01:24,200 --> 00:01:27,240 Speaker 1: Hopefully I got that right. He's a professor at the 21 00:01:27,280 --> 00:01:33,120 Speaker 1: Center of Molecular Medicine in gch Medical University in Japan. 22 00:01:33,560 --> 00:01:36,320 Speaker 1: Him and his team were studying hypertension or high blood 23 00:01:36,319 --> 00:01:39,760 Speaker 1: pressure in mice, and they were tweaking their genes to 24 00:01:39,880 --> 00:01:46,039 Speaker 1: try to understand how altering specific amino acids affected sodium 25 00:01:46,040 --> 00:01:49,640 Speaker 1: transport that could then impact on their blood pressure. But 26 00:01:49,840 --> 00:01:53,760 Speaker 1: one group of mice, after just a few small genetic changes, 27 00:01:54,200 --> 00:01:58,440 Speaker 1: started to age at a really alarming rate. And these mice, 28 00:01:58,520 --> 00:02:01,120 Speaker 1: which should have lived for about two and a half years, 29 00:02:01,520 --> 00:02:06,040 Speaker 1: were barely surviving for three months. So the researchers then 30 00:02:06,160 --> 00:02:10,520 Speaker 1: trace this rapid aging back to a single gene, which 31 00:02:10,560 --> 00:02:15,400 Speaker 1: he named Clotho, after the Greek goddess who spins the 32 00:02:15,520 --> 00:02:18,600 Speaker 1: threat of life. That's pretty cool, isn't it. Now. From there, 33 00:02:19,000 --> 00:02:21,920 Speaker 1: the scientists wanted to see what would happen if the 34 00:02:22,080 --> 00:02:24,440 Speaker 1: opposite occurred, As you obviously word if you were him, 35 00:02:24,840 --> 00:02:29,800 Speaker 1: what happens if you overexpress the CLOTHO gene? And sure enough, 36 00:02:29,800 --> 00:02:33,280 Speaker 1: when they did this in mice, their lifespans increased by 37 00:02:33,320 --> 00:02:38,560 Speaker 1: a whopping thirty percent. That's clearly a massive jump, and 38 00:02:38,600 --> 00:02:42,800 Speaker 1: it showed that CLOTHO is essential for longevity. Now, CLOTHO 39 00:02:43,040 --> 00:02:46,880 Speaker 1: is a protein that's produced mostly by our kidneys, and 40 00:02:46,919 --> 00:02:49,520 Speaker 1: there's a bit of it produced in the brain, and 41 00:02:49,560 --> 00:02:53,760 Speaker 1: it's pretty large protein compared to other proteins, and its 42 00:02:53,960 --> 00:02:58,760 Speaker 1: active form gets clipped off and circular. It's throughout the body, 43 00:02:59,360 --> 00:03:01,959 Speaker 1: just like a whole. And think of it the way 44 00:03:02,000 --> 00:03:05,800 Speaker 1: that insulin acts. So insulin starts as a larger molecule 45 00:03:06,200 --> 00:03:09,240 Speaker 1: that then gets cut off and goes about doing its job. 46 00:03:09,720 --> 00:03:12,600 Speaker 1: And in this case, the job of CLOTHO is to 47 00:03:12,639 --> 00:03:16,560 Speaker 1: protect sales from damage, especially in the brain and the 48 00:03:16,600 --> 00:03:22,160 Speaker 1: cardiovascular system. However, scientists have discovered that CLOTHO doesn't actually 49 00:03:22,320 --> 00:03:26,240 Speaker 1: cross the blood brain barrier, which raises the obvious question, 50 00:03:26,919 --> 00:03:29,480 Speaker 1: how can it have all of these beneficial effects in 51 00:03:29,520 --> 00:03:32,760 Speaker 1: the brain if it never actually reaches there. Well, this 52 00:03:32,880 --> 00:03:35,720 Speaker 1: is why the science starts to get really interesting. And 53 00:03:35,800 --> 00:03:40,520 Speaker 1: it turns out from subsequent research that CLOTHO actually increases 54 00:03:40,560 --> 00:03:46,280 Speaker 1: a molecule called platelet factor four or PF four in 55 00:03:46,360 --> 00:03:50,320 Speaker 1: the body, and PF four does actually cross the blood 56 00:03:50,320 --> 00:03:53,840 Speaker 1: brain barrier, and once it's in the brain, PF four 57 00:03:54,040 --> 00:03:58,480 Speaker 1: interacts with certain receptors that help to improve brain plasticity. 58 00:03:58,720 --> 00:04:01,240 Speaker 1: So you may have heard me talk about and plasticity before. 59 00:04:01,400 --> 00:04:05,080 Speaker 1: In simple terms, it helps to keep your brain flexible, 60 00:04:05,400 --> 00:04:09,840 Speaker 1: which is essential for learning, memory and protecting against cognitive decline. 61 00:04:10,280 --> 00:04:12,760 Speaker 1: So let's talk a bit more about clotho's impact on 62 00:04:12,920 --> 00:04:16,360 Speaker 1: brain health because this is where stuff really does start 63 00:04:16,400 --> 00:04:19,960 Speaker 1: to get interesting. So researchers have since been experimenting with 64 00:04:20,080 --> 00:04:24,839 Speaker 1: CLOTHO in animal models to better understand its potential benefits, 65 00:04:24,960 --> 00:04:28,719 Speaker 1: especially for cognition and memory. And in one of the 66 00:04:28,760 --> 00:04:33,640 Speaker 1: most interesting studies for me, researchers looking at macaques, which 67 00:04:33,640 --> 00:04:36,679 Speaker 1: are a type of monkey, and give them a single 68 00:04:36,720 --> 00:04:39,840 Speaker 1: injection of CLOTHO. Now, they weren't sick monkeys, although it 69 00:04:39,880 --> 00:04:43,000 Speaker 1: didn't even have a cognitive decline. They were healthy, middle 70 00:04:42,960 --> 00:04:47,000 Speaker 1: aged monkeys, and this makes the results more interesting. Within 71 00:04:47,279 --> 00:04:51,040 Speaker 1: just four hours of receiving the CLOTHO injection, these monkeys 72 00:04:51,040 --> 00:04:56,000 Speaker 1: showed significant improvement in a range of cognitive tasks and 73 00:04:56,080 --> 00:04:59,920 Speaker 1: particularly in spatial memory. Basically that's the ability to ren 74 00:05:00,080 --> 00:05:03,360 Speaker 1: member and navigate spaces, which are really important for lots 75 00:05:03,360 --> 00:05:06,840 Speaker 1: of species. And get this, the cognitive boost that they 76 00:05:06,880 --> 00:05:11,400 Speaker 1: got lasted for three to four weeks after a single injection, 77 00:05:11,839 --> 00:05:14,680 Speaker 1: and it was if their brain had been dialed back 78 00:05:14,720 --> 00:05:19,039 Speaker 1: to a younger, more flexible state. Now, this experiment is 79 00:05:19,120 --> 00:05:23,359 Speaker 1: a pretty big deal in particular because lots of mice 80 00:05:23,440 --> 00:05:27,760 Speaker 1: experiments showed similar things. But as you've often heard me say, 81 00:05:28,360 --> 00:05:32,320 Speaker 1: mice are pretty distant to humans, and lots of things 82 00:05:32,320 --> 00:05:35,919 Speaker 1: that work in mice actually don't work in primates. But 83 00:05:36,080 --> 00:05:38,760 Speaker 1: here the results are pretty clear. Now, if this could 84 00:05:38,760 --> 00:05:42,440 Speaker 1: work in humans, and studies are ongoing, it could be 85 00:05:42,480 --> 00:05:46,640 Speaker 1: a game changer for those facing cognitive decline, people with 86 00:05:46,680 --> 00:05:50,520 Speaker 1: Alzheimer's disease or mild cognitive imperment or other forms of dementia. 87 00:05:50,600 --> 00:05:54,000 Speaker 1: And actually animal studies is currently ongoing in those areas 88 00:05:54,360 --> 00:05:57,599 Speaker 1: as well as als in animal studies, and it's showing 89 00:05:57,600 --> 00:05:59,960 Speaker 1: a fur bit of promise. So if we go back 90 00:06:00,080 --> 00:06:04,360 Speaker 1: to Alzheimer's disease, there's more evidence pointing to clotho's protective 91 00:06:04,400 --> 00:06:09,880 Speaker 1: effects in mice that are genetically predisposed to develop Alzheimer's disease. 92 00:06:09,920 --> 00:06:13,200 Speaker 1: So what they do is they edit their genes over 93 00:06:13,320 --> 00:06:17,080 Speaker 1: express the APOEE four genes and maybe some other ones. 94 00:06:18,160 --> 00:06:22,440 Speaker 1: What they did, scientists increased the CLOTHO expression to levels 95 00:06:22,440 --> 00:06:26,120 Speaker 1: that mirrored what these mice would have when they were 96 00:06:26,160 --> 00:06:28,440 Speaker 1: born or when they were young. Because our CLOTHO tends 97 00:06:28,480 --> 00:06:31,320 Speaker 1: to decline over the years, and what they found was 98 00:06:31,400 --> 00:06:35,920 Speaker 1: pretty remarkable. Despite the fact that these mice still developed 99 00:06:36,360 --> 00:06:40,560 Speaker 1: the classic amyloid plaques that are associated with Alzheimer's disease, 100 00:06:40,920 --> 00:06:44,760 Speaker 1: they did not experience the same level of cognitive decline, 101 00:06:45,240 --> 00:06:52,280 Speaker 1: and actually, over expressing CLOTHO completely nullified the increased risk 102 00:06:52,360 --> 00:06:55,480 Speaker 1: of Alzheimer's disease for having the bad genes, if you like, 103 00:06:55,560 --> 00:06:58,880 Speaker 1: for Alzheimer's. So essentially what happened was CLOTHO made their 104 00:06:58,880 --> 00:07:03,480 Speaker 1: brains more rezs to the damage caused by amyloid built up, 105 00:07:03,560 --> 00:07:08,400 Speaker 1: and this is maybe why millions upon millions upon millions 106 00:07:08,520 --> 00:07:11,560 Speaker 1: of research strugs to try and clear amyloid from the 107 00:07:11,640 --> 00:07:16,720 Speaker 1: brain have actually not impacted on Alzheimer's disease and certainly 108 00:07:17,120 --> 00:07:19,880 Speaker 1: on the symptoms of it. So it may be and 109 00:07:20,320 --> 00:07:23,520 Speaker 1: a lot of researchers think this that amoloid isn't the cause. 110 00:07:23,960 --> 00:07:27,160 Speaker 1: It's the brain brand to protect, whether it's against inflammation 111 00:07:27,280 --> 00:07:32,440 Speaker 1: or something else. But this research suggests that clotho may 112 00:07:32,640 --> 00:07:35,840 Speaker 1: not be able to undo the damage that's already occurred, 113 00:07:36,400 --> 00:07:40,000 Speaker 1: but it may be protective and make the brain less 114 00:07:40,040 --> 00:07:45,200 Speaker 1: susceptible to harm. And the implications for treatment of humans 115 00:07:45,240 --> 00:07:49,280 Speaker 1: are enormous, especially as we look for ways to not 116 00:07:49,360 --> 00:07:52,840 Speaker 1: treat Alzheimer's but prevent it all together. And a lot 117 00:07:52,920 --> 00:07:56,440 Speaker 1: of the researchers focused on prevention because once you got it, 118 00:07:56,440 --> 00:08:01,000 Speaker 1: it's so hard to do anything about Now. Inhuman CLOTHO 119 00:08:01,120 --> 00:08:05,280 Speaker 1: levels vary and some people are born, some lucky people 120 00:08:05,400 --> 00:08:11,240 Speaker 1: with a genetic variant called KLVS. And actually, if you've 121 00:08:11,240 --> 00:08:14,600 Speaker 1: had a genetic test such as twenty three and meters, 122 00:08:15,040 --> 00:08:19,120 Speaker 1: you can actually look up this snip. You can pop 123 00:08:19,160 --> 00:08:22,200 Speaker 1: it into the testing of the snips and it will 124 00:08:22,200 --> 00:08:26,400 Speaker 1: actually pop up about what variant you have. Unfortunately I 125 00:08:26,440 --> 00:08:29,480 Speaker 1: don't have the one that overexpresses it. But if you 126 00:08:29,600 --> 00:08:34,080 Speaker 1: have one copy of the KLVS variant, you naturally produce 127 00:08:34,120 --> 00:08:37,920 Speaker 1: about fifteen percent more CLOTHO than those without it. And 128 00:08:37,960 --> 00:08:42,040 Speaker 1: this extra CLOTHO is linked to longer lifespans, better brain function, 129 00:08:42,520 --> 00:08:45,959 Speaker 1: and even reduced risk of Alzheimer's disease, especially in people 130 00:08:46,000 --> 00:08:49,960 Speaker 1: with that apoe four gene that I say is normally 131 00:08:50,000 --> 00:08:53,160 Speaker 1: associated with the higher risk. But here's the flip side. 132 00:08:53,559 --> 00:08:58,000 Speaker 1: If you had two copies of the VS variant, you 133 00:08:58,080 --> 00:09:02,880 Speaker 1: actually end up with less clothough, about thirty percent less, 134 00:09:03,360 --> 00:09:07,160 Speaker 1: and that's associated with much worse cognitive outcomes and a 135 00:09:07,360 --> 00:09:11,400 Speaker 1: shorter lifespan. So it's clear that not everybody starts at 136 00:09:11,400 --> 00:09:14,360 Speaker 1: the same baseline when it comes to CLOTHO. Some people 137 00:09:14,440 --> 00:09:17,960 Speaker 1: win the genetic lottery, some people are middling, and some 138 00:09:18,000 --> 00:09:21,520 Speaker 1: people lose the genetic lottery. Now this is why some 139 00:09:21,720 --> 00:09:25,640 Speaker 1: very wealthy people are now actually getting their genes edited. 140 00:09:25,760 --> 00:09:28,640 Speaker 1: So there's a process called Crisper where you can go 141 00:09:28,679 --> 00:09:32,040 Speaker 1: and edit your genes and they can end up with 142 00:09:32,080 --> 00:09:35,480 Speaker 1: a variant that over expresses CLOTHO. So there's one such 143 00:09:35,960 --> 00:09:40,560 Speaker 1: example was reported in the Australian newspaper The Financial Review 144 00:09:40,600 --> 00:09:44,079 Speaker 1: in May this year, and he's a rich lister called 145 00:09:44,240 --> 00:09:47,720 Speaker 1: Nick Bell. He's a health and fitness evangelist who just 146 00:09:47,760 --> 00:09:52,160 Speaker 1: spent seven hundred grand on Crisper injections to alter his 147 00:09:52,280 --> 00:09:56,000 Speaker 1: genes so that they can improve his brain function and 148 00:09:56,160 --> 00:09:58,160 Speaker 1: also improve his muscle mass and strength. So there are 149 00:09:58,160 --> 00:10:03,360 Speaker 1: two treatments that he got were tweaks to the CLOTHO 150 00:10:03,480 --> 00:10:07,960 Speaker 1: gene and fall of statin. Now, fall of statin actually 151 00:10:08,000 --> 00:10:11,240 Speaker 1: inhibits mile statin. We're going off track a little bit here, 152 00:10:11,280 --> 00:10:14,960 Speaker 1: but myostatin is the one mile kind that stops you 153 00:10:15,120 --> 00:10:21,520 Speaker 1: producing too much muscle and when they actually block that 154 00:10:22,520 --> 00:10:28,320 Speaker 1: milestatin and you just look up just Google and mice 155 00:10:29,120 --> 00:10:33,600 Speaker 1: without are with myostatin knockout and they look like arnold 156 00:10:33,600 --> 00:10:37,319 Speaker 1: Sportznigger versions of mice. So if you can't lazy seven 157 00:10:37,440 --> 00:10:40,679 Speaker 1: hundred grand sitting around, you could probably go and do that. 158 00:10:40,720 --> 00:10:42,560 Speaker 1: Maybe the cloth the ones half the price, I'm not 159 00:10:42,600 --> 00:10:46,599 Speaker 1: really sure, But if you don't have that amount of 160 00:10:46,640 --> 00:10:49,600 Speaker 1: money to spend editing your genes, there is some really 161 00:10:49,600 --> 00:10:52,720 Speaker 1: good news you can all of us can increase our 162 00:10:52,760 --> 00:10:57,080 Speaker 1: CLOTHO levels regardless of your genetic starting point. And this 163 00:10:57,200 --> 00:10:59,280 Speaker 1: is the really important part that I want you to remember. 164 00:10:59,600 --> 00:11:04,199 Speaker 1: No matter of what your genetic makeup is, exercise increases 165 00:11:04,360 --> 00:11:08,960 Speaker 1: your CLOTHO levels pretty dramatically, and not a lot of 166 00:11:09,000 --> 00:11:11,600 Speaker 1: you will be surprised that it's exercised, is the one 167 00:11:11,600 --> 00:11:16,199 Speaker 1: that I'm focusing in on. We know that regular physical 168 00:11:16,200 --> 00:11:20,280 Speaker 1: activity can actually give you a greater boosting CLOTHO than 169 00:11:20,320 --> 00:11:25,040 Speaker 1: the lucky people who over express it get from their genetics. 170 00:11:24,640 --> 00:11:29,000 Speaker 1: And there's one study that showed that twelve weeks of consistent, 171 00:11:29,440 --> 00:11:35,080 Speaker 1: pretty intense exercise participants saw an average thirty percent increase 172 00:11:35,120 --> 00:11:37,880 Speaker 1: in their CLOTHO levels. So put out in the perspective. 173 00:11:37,960 --> 00:11:41,319 Speaker 1: That's double the cloth O boost that people with one 174 00:11:41,440 --> 00:11:45,480 Speaker 1: variant of the KLVS variant actually get. And we're talking 175 00:11:45,480 --> 00:11:49,920 Speaker 1: about real measurable health benefits here, and this is another 176 00:11:50,120 --> 00:11:55,880 Speaker 1: reason why exercise is the best longevity medicine that there is. 177 00:11:55,920 --> 00:11:59,400 Speaker 1: As well as enhancing CLOTHO, there's all of those maya 178 00:11:59,520 --> 00:12:01,840 Speaker 1: kinds that have been produced that you'll have heard me 179 00:12:02,040 --> 00:12:06,400 Speaker 1: banging on about, but this particularly seems to be why 180 00:12:06,480 --> 00:12:10,800 Speaker 1: people who regularly exercise might have better cognitive health because 181 00:12:10,880 --> 00:12:14,679 Speaker 1: they are significantly improving their cloth O levels, and so 182 00:12:14,720 --> 00:12:17,400 Speaker 1: they'll get lower levels of cognitive decline and probably even 183 00:12:17,520 --> 00:12:20,240 Speaker 1: improve longevity, which is what we see particularly for people 184 00:12:20,559 --> 00:12:24,280 Speaker 1: who do a reasonable amount of high intensity exercise, and 185 00:12:24,320 --> 00:12:28,199 Speaker 1: the benefits don't stop there. Exercise doesn't only increase your 186 00:12:28,200 --> 00:12:32,240 Speaker 1: CLOTHO levels, but it also taps into the same pathways 187 00:12:32,240 --> 00:12:34,920 Speaker 1: that protect your brain and improve your memory. So it's 188 00:12:35,120 --> 00:12:39,960 Speaker 1: like giving your brain a protective shield while also improving 189 00:12:40,000 --> 00:12:44,319 Speaker 1: your body's overall health. So here's the big takeaway. Cloth though, 190 00:12:44,800 --> 00:12:50,280 Speaker 1: is a very powerful longevity promoting gene that has got 191 00:12:50,280 --> 00:12:54,320 Speaker 1: a really good evidence based ny in animal studies and 192 00:12:54,400 --> 00:12:57,560 Speaker 1: in primeates, and it appears to protect your brain and 193 00:12:57,600 --> 00:13:00,120 Speaker 1: help you live longer. And whilst some people do of 194 00:13:00,160 --> 00:13:04,080 Speaker 1: a genetic advantage when it comes to CLOTHO levels, everybody 195 00:13:04,200 --> 00:13:07,920 Speaker 1: has the ability to increase their cloth through regular exercise. 196 00:13:08,400 --> 00:13:10,960 Speaker 1: So I want you to think of exercise here. This 197 00:13:11,000 --> 00:13:14,200 Speaker 1: is the big takeout as your ticket to better brain health, 198 00:13:14,600 --> 00:13:17,920 Speaker 1: a longer life, and a body that's more resilient to 199 00:13:17,960 --> 00:13:21,520 Speaker 1: the challenges of aging. Well, it's not just about keeping fit, 200 00:13:22,000 --> 00:13:25,520 Speaker 1: it's about boosting the expression of one of the most 201 00:13:25,640 --> 00:13:31,000 Speaker 1: important genes linked to longevity and good brain health. So 202 00:13:31,080 --> 00:13:33,960 Speaker 1: that's it for today. So if you want to live longer, 203 00:13:34,000 --> 00:13:37,200 Speaker 1: protect your brain and feel better overall, you just gotta 204 00:13:37,280 --> 00:13:41,080 Speaker 1: make exercise the core component of your routine and make 205 00:13:41,120 --> 00:13:44,760 Speaker 1: sure you sprinkle in some vigorous stuff. Catch you next time.