WEBVTT - Wisdom Wednesday - Anti-aging strategies part 5 - combatting the loss of Proteostasis 0:00:08.880 --> 0:00:12.280 Everyone, Welcome to another edition of Wisdom Wednesdays, and this 0:00:12.800 --> 0:00:16.560 is the fifth podcast in our series on the hallmarks 0:00:16.560 --> 0:00:20.000 of aging and more importantly, what we can do about it. So, Terry, 0:00:21.680 --> 0:00:27.600 the loss of proteostasis, which basically refers to high well 0:00:27.800 --> 0:00:32.720 we manage our cells proteins, or the proteins within our cells, 0:00:33.640 --> 0:00:37.040 whether we can keep them correctly folded and functional and 0:00:37.120 --> 0:00:42.000 free from damage. So we know that and amino acids 0:00:42.000 --> 0:00:45.320 are really the workhorses of our cells. So the proteins 0:00:45.360 --> 0:00:48.840 are obviously made up of amino acids. But what proteins 0:00:48.840 --> 0:00:53.120 do inside the cell is they build and repair our tissues, 0:00:53.680 --> 0:00:58.760 and they transport molecules, they catalyze essential biochemical reactions and 0:00:58.840 --> 0:01:06.160 do so. But as we age, our ability to maintain protostasis, 0:01:06.160 --> 0:01:12.039 which basically means protein homeostasis or protein balance, that actually declines, 0:01:12.640 --> 0:01:15.720 and this leads to the accumulation of what we call 0:01:16.000 --> 0:01:23.679 misfolded and damage proteins, which contributes to Timer's disease, Parkinson's disease, cancer, 0:01:23.920 --> 0:01:28.679 and general tissue degeneration. Now, the good news is that 0:01:28.760 --> 0:01:31.680 there is lifestyle choices that we can make that can 0:01:31.760 --> 0:01:35.840 slow this process down. And this loss of proteo stasis 0:01:35.880 --> 0:01:41.480 and can actually enhance our protein maintenance and support. So 0:01:41.600 --> 0:01:43.039 first of all, let's do a bit of a dive 0:01:43.080 --> 0:01:46.679 into proteostasis and why it's important. So it is really 0:01:46.720 --> 0:01:52.640 the delicate balance of protein production, folding, maintenance, and degradation 0:01:52.800 --> 0:01:55.720 within our cells. And this system involves a number of 0:01:55.720 --> 0:01:59.320 different things. So the first one is protein synthesis, so 0:01:59.400 --> 0:02:03.000 this is about proteins from the building blocks of proteins, 0:02:03.040 --> 0:02:06.760 which are amino acids. And then we have protein folding, 0:02:07.200 --> 0:02:10.880 so this ensures that proteins take on the correct shape 0:02:10.919 --> 0:02:14.440 to function properly, and the shape of the protein actually 0:02:14.480 --> 0:02:18.920 determines its function. And then we have these protein quality 0:02:19.000 --> 0:02:25.160 control mechanism mechanisms that detect and repair our misfolded proteins, 0:02:25.200 --> 0:02:27.040 and we're going to talk about how we can upregulate 0:02:27.080 --> 0:02:30.040 some of those. And then the last thing is about 0:02:30.120 --> 0:02:35.160 protein degradation, So this is about removing damaged or dysfunctional 0:02:35.280 --> 0:02:41.079 proteins through cellular cleanup mechanisms like autophogy, which you'll talk 0:02:41.160 --> 0:02:44.800 about before, or are Another way to do this is 0:02:44.840 --> 0:02:49.799 something called the ubiquitin proteosome system right bit complex, but 0:02:49.800 --> 0:02:54.080 it's basically cellular cleanup. Now, when all these systems are 0:02:54.120 --> 0:02:58.239 working well, our cells functioning optimally, they remain resilient to 0:02:58.360 --> 0:03:04.480 stress and they can quick environmental changes. But when protostasis 0:03:04.520 --> 0:03:08.480 breaks down, that's when we get these damage proteins accumulating, 0:03:08.600 --> 0:03:13.880 leading to cellular dysfunction, inflammation, and chronic disease. Now, as 0:03:13.919 --> 0:03:17.120 we aige, there's a number of things that interfere with 0:03:17.200 --> 0:03:21.320 this protein balance. So the first of all, first is 0:03:21.480 --> 0:03:25.720 decline in what we call molecular chaperones. So chaperones are 0:03:25.720 --> 0:03:29.760 proteins that actually help other proteins fold correctly. They're like 0:03:29.800 --> 0:03:33.760 the janitors of the cell. So aging reduces the activity 0:03:33.800 --> 0:03:38.520 of these chaperones, increasing the risk of protein misfolding and aggregation. 0:03:39.040 --> 0:03:45.240 And then the second is imperatophogy and proteosome function. So 0:03:45.400 --> 0:03:49.560 autophogy is the process by which cells break down and 0:03:49.920 --> 0:03:53.120 recycle damage proteins, and they actually it's very clever. They 0:03:53.480 --> 0:03:57.640 recycle this stuff and actually use the energy for other 0:03:57.720 --> 0:04:02.360 functions in the cell. And as we age, g starts 0:04:02.360 --> 0:04:05.280 their system starts to slow down, which causes a buildup 0:04:05.320 --> 0:04:09.400 of toxic protein aggregates as we see in Alzheimer's disease. 0:04:09.800 --> 0:04:11.680 And then the proteosome. 0:04:11.960 --> 0:04:16.200 That's another cleanup system that tags and removes faulty proteins, 0:04:16.440 --> 0:04:21.000 and that also loses its efficiency over time. Then it 0:04:21.240 --> 0:04:26.240 interferes with protein balances oxided of stress and inflammation, and 0:04:26.279 --> 0:04:29.440 we talked about inflammating last week, and you see all 0:04:29.440 --> 0:04:33.640 of these things are interrelated, right. So free radicals, which 0:04:33.640 --> 0:04:38.719 you'll probably know, are unstable molecules, they actually damage proteins, 0:04:39.200 --> 0:04:43.680 increasing our cellular cleanup systems. So what we're going to 0:04:43.760 --> 0:04:46.440 do is try and improve the cellular cleanup system and 0:04:46.520 --> 0:04:49.320 make sure it doesn't degrade too much, but then also 0:04:49.680 --> 0:04:54.120 minimize the damage that's coming into the sale. And then 0:04:54.200 --> 0:04:58.839 chronic inflammation then further disrupts this proteo stasis. After we 0:04:58.920 --> 0:05:03.000 have these free radicals, the last thing is the accumulation 0:05:03.160 --> 0:05:09.240 of these protein aggregates. So neurodegeneric diseases like Alzheimer's and Parkinson's, 0:05:09.760 --> 0:05:14.280 we see these abnormal proteins. In an Alzheimer's disease, they're 0:05:14.279 --> 0:05:18.560 called beta amyloid and tauel proteins, and in Parkinson's disease, 0:05:18.640 --> 0:05:24.000 it's alphasin nuclear that accumulates, leading to neural damage. So 0:05:24.120 --> 0:05:27.039 let's talk about the stuff that we can do. First, 0:05:27.040 --> 0:05:29.240 cab off the rank. You'll not be surprised to hear 0:05:29.760 --> 0:05:32.400 is exercise, and it is actually one of the most 0:05:32.480 --> 0:05:37.560 powerful ways to enhance proteostasis and prevent the buildup of 0:05:37.640 --> 0:05:41.880 damage proteins. So here's how it works. We know that 0:05:42.080 --> 0:05:46.480 exercise boosts autophogy. There's a heap of research that shows 0:05:46.480 --> 0:05:50.279 that it boosts autoplogy the cellular cleaner, particularly in muscle cells, 0:05:50.720 --> 0:05:53.600 and it helps to clear out these misfolded or damage 0:05:53.640 --> 0:05:58.839 proteins before they accumulate to onhealthy levels. And we know 0:05:58.920 --> 0:06:04.000 that both high intents and endurance exercise are particularly effective 0:06:04.040 --> 0:06:09.120 in stimulating utopogy, and some research suggests that exercising in 0:06:09.200 --> 0:06:14.080 a fasted ste it can actually enhance that autophogy within 0:06:14.440 --> 0:06:18.800 the muscle cells. The next way that exercise actually helps 0:06:19.040 --> 0:06:23.120 is that it in what we call heat shop proteins. 0:06:23.440 --> 0:06:27.359 So these are these molecular chaperones that I talked about, 0:06:27.360 --> 0:06:29.280 and I've talked about heat shop proteins. 0:06:28.920 --> 0:06:30.719 For years and I love them. 0:06:31.000 --> 0:06:34.719 These are these molecular These are molecules or chaperoons that 0:06:34.800 --> 0:06:39.840 assist in protein folding and repair and basically they get 0:06:39.880 --> 0:06:43.800 RELI exercise and then they run around and look for 0:06:43.880 --> 0:06:47.680 damage proteins and they band them into the correct shape 0:06:47.960 --> 0:06:51.880 and then they hang around the cell to actually protect 0:06:51.920 --> 0:06:56.359 against further damage. So every time you're exercising, you're increasing 0:06:56.400 --> 0:06:59.839 the amount of janitors or workhorses within the cell to 0:07:01.440 --> 0:07:04.479 and that and all these heat shock proteins help to 0:07:04.520 --> 0:07:08.360 prevent protein aggregation, which is that major issue we talked 0:07:08.360 --> 0:07:12.160 about in neurodegenera of diseases. Another reason that exercise is 0:07:12.240 --> 0:07:16.160 useful is it reduces oxidative stress and inflammation. So on 0:07:16.160 --> 0:07:19.400 one side of the ledger it's improving the cleanup and 0:07:19.480 --> 0:07:22.920 then the other thing the amount of damage. So we 0:07:23.000 --> 0:07:27.640 know that exercise produces free radicals, but it also stimulates 0:07:27.680 --> 0:07:33.400 our antioxidant defense system and particularly are in dodgenous antioxidant defense, 0:07:33.440 --> 0:07:41.280 so it upregulates glutotherrem parioxidase, catalas and superoxide dismutate the 0:07:41.440 --> 0:07:44.440 special forces of your antioxidant defense system. 0:07:44.880 --> 0:07:45.440 And it's been. 0:07:45.400 --> 0:07:50.760 Shown that strength training, anaerobic exercise or endurance exercise lowers 0:07:50.880 --> 0:07:54.920 levels of pro inframetory side of kinds such as interluting 0:07:55.040 --> 0:07:59.280 six TNF alphon and C reactive protein, and therefore it 0:07:59.400 --> 0:08:03.960 reduces in humleostasis system. And we know that exercise also 0:08:04.680 --> 0:08:08.720 increases the activity of anti inflammatory side accounts such as 0:08:08.760 --> 0:08:13.800 interlooking ten and then exercise. The fourth way that it 0:08:13.880 --> 0:08:18.200 works is it supports our mitochondrial health. So our mitochondria 0:08:18.280 --> 0:08:22.880 they generate atp or energy and aging in personal function, 0:08:23.360 --> 0:08:26.560 and that leads to protein damage from excess free radicals. 0:08:26.840 --> 0:08:31.080 We know that exercise not only enhances our mitochondrial efficiency, 0:08:31.680 --> 0:08:36.480 therefore reducing protein ox oxidation and helping to support proteostasis, 0:08:36.840 --> 0:08:42.880 but high intensity infoltraining actually drives out genesis brands spanking 0:08:43.000 --> 0:08:47.400 new batteries in your sales. So exercise for me is 0:08:47.440 --> 0:08:51.240 an absolute cornerstone for proteo stasis. But there's other things 0:08:51.320 --> 0:08:54.520 that we can do to maintain proteostasis. Now, because this 0:08:54.640 --> 0:08:57.920 is all of our proteins. Eating a high quality protein 0:08:57.960 --> 0:09:02.080 diet is really really key. And I've said this many 0:09:02.120 --> 0:09:05.440 times before, but I'll say it again, especially as we 0:09:05.520 --> 0:09:09.640 get older, and when you're sick, you need more protein, 0:09:09.760 --> 0:09:14.280 so we develop anabolic resistance as we get older. Now, 0:09:14.600 --> 0:09:22.520 the old rdies referenced are the daily intakes that they 0:09:22.559 --> 0:09:26.800 were not point eight grams per kilogram of protein of 0:09:27.480 --> 0:09:31.400 not pointy eight grams of protein per kilogram of body 0:09:31.400 --> 0:09:36.640 weights right now, those referenced nutrient intakes are like fifty 0:09:36.720 --> 0:09:41.920 years old, and they were based on Dodge studies at 0:09:41.920 --> 0:09:45.240 the time, and most researchers now I say that that 0:09:45.360 --> 0:09:49.200 is way suboptimal. That we need between one point four 0:09:49.760 --> 0:09:53.560 and two to two point two grams per kilogram of 0:09:53.720 --> 0:09:58.440 protein of our body weight. So for me at eighty kilos, 0:09:58.880 --> 0:10:03.240 that's about a to one hundred and sixty grams of protein, 0:10:03.400 --> 0:10:07.160 and especially as you get older, you need that upper limit. 0:10:07.280 --> 0:10:12.800 And making sure you're having good quality proteins and meat 0:10:12.960 --> 0:10:16.199 is generally the best source if you're vegan, making sure 0:10:16.679 --> 0:10:21.720 that you are vegetarian, that you're combining just like rice 0:10:21.760 --> 0:10:27.000 and beans, and for a lot of people they also 0:10:27.160 --> 0:10:30.920 need to probably take some sort of protein supplement in 0:10:30.960 --> 0:10:34.240 a good quality, whether it's grass fed, wave protein or 0:10:34.280 --> 0:10:36.480 a pay protein if you're vegetarian or vegan. 0:10:36.920 --> 0:10:37.840 And making sure you're. 0:10:37.679 --> 0:10:44.080 Having enough loucine because lousing that stimulates muscle protein synthesis. 0:10:44.200 --> 0:10:46.880 You find that in eggs and dirty but also in legoons, 0:10:47.400 --> 0:10:51.000 and that will really help. So we've got to have 0:10:51.160 --> 0:10:54.760 that high protein diet and lots of people just do 0:10:54.960 --> 0:10:59.040 not eat enough protein, especially as we age, and this 0:10:59.160 --> 0:11:00.120 is an aging. 0:11:01.600 --> 0:11:03.960 It should really underscore the importance of this. 0:11:04.840 --> 0:11:09.840 Next is consuming anti inflammatory and antioxidant foods, so polyphenols 0:11:09.880 --> 0:11:14.600 and flavonoids that we find in berries, green tea, dark chocolate, 0:11:14.679 --> 0:11:18.280 but also fruits, lots of fruits and vegetables and gin. 0:11:18.400 --> 0:11:22.640 Seeing all of these things they sort of stress. We 0:11:22.720 --> 0:11:27.240 know the mega three fatty acids really reduce inflammation and 0:11:27.280 --> 0:11:31.480 support brain proteo stasis. And curcumin which you get from 0:11:31.520 --> 0:11:35.480 turmeric and particularly when taken with black pepper or peppering, 0:11:35.920 --> 0:11:41.319 and that enhances autophagy, is anti inflammatory and reduce holding. 0:11:41.480 --> 0:11:42.679 So making sure that. 0:11:42.640 --> 0:11:47.720 We're having a good quality diet with lots of fresh 0:11:47.720 --> 0:11:51.600 fruit and vegetables, things like berries, green tea, dark chocolate, gin, 0:11:51.720 --> 0:11:56.640 sing ginger, those sorts of things will really and turmeric 0:11:56.960 --> 0:11:59.840 our curcumin will really help. And then it's about getting 0:11:59.840 --> 0:12:04.880 an because that is critical for protein repair and maintenance. 0:12:05.080 --> 0:12:09.520 Most of our maintenance and repairer functions happen when we're sleep, 0:12:10.120 --> 0:12:13.960 and when we don't have good sleep, it disrupts utophagy 0:12:14.320 --> 0:12:19.000 and it disrupts this chaperum protein function. Which then accelerates 0:12:19.000 --> 0:12:24.800 our protein damage. But in avoiding or minimizing your toxins right, 0:12:25.200 --> 0:12:30.280 whether that's from smoking, vaping, pollution, and heavy alcohol use, 0:12:30.559 --> 0:12:34.000 and they all increase oxidative stress leading to protein damage. 0:12:34.240 --> 0:12:38.239 And then ultra process foods, they contain lots of additives 0:12:38.240 --> 0:12:42.280 that are known to empower protein. It's another thing to 0:12:42.440 --> 0:12:47.400 really think about. And then some targeted supplements. Nac nacetyl 0:12:47.440 --> 0:12:53.160 systein is an absolute cracking supplement. It supports gluedothion production 0:12:53.240 --> 0:12:56.679 that's the master or antioxidant in the body, and it 0:12:56.720 --> 0:12:59.120 protects proteins from oxidative stress. 0:13:00.960 --> 0:13:02.240 I've talked about that before. 0:13:02.320 --> 0:13:07.200 That's a mix of knack and glycing, the amino acid glycing, 0:13:07.840 --> 0:13:11.920 and research that I've talked about before shows that it's 0:13:12.000 --> 0:13:19.120 anti It improves our antioxidant status. It also enhances lifespan 0:13:19.360 --> 0:13:23.920 in mice. Not only does it improve antioxidant status, but 0:13:24.440 --> 0:13:27.440 so A couple of research papers of note for this 0:13:28.440 --> 0:13:32.000 one and the title of Atophogy and Aging Maintaining the 0:13:32.040 --> 0:13:37.120 Proteum through Exercise that was produced in twenty twelve, and 0:13:37.160 --> 0:13:43.360 it showed that endurance exercise increases arious tissues. And other 0:13:43.360 --> 0:13:46.360 studies have shown that resistance training actually does the same thing. 0:13:46.920 --> 0:13:50.559 And then another one about resistance training, the effect of 0:13:50.600 --> 0:13:55.160 resistance training on heat shop protein response heat shop protein 0:13:55.280 --> 0:13:59.360 seventy oxident of stress, inflammation, body composition, and metabolism in 0:13:59.400 --> 0:14:04.920 Middle Ages, basically showed that a resistance training increases heat 0:14:04.960 --> 0:14:09.280 chok protein, especially heat shop protein seventy, which is very 0:14:09.400 --> 0:14:14.280 very protective, and that actually reminded me of other ways 0:14:14.320 --> 0:14:18.360 to increase heat shok proteins. We know that sauna use, 0:14:18.559 --> 0:14:24.360 regular sauna use, this is heat chok protein activity. And 0:14:25.360 --> 0:14:29.360 it was particularly the research that I've seen was twenty 0:14:29.440 --> 0:14:32.400 minutes at eighty degrees. Now this was in a traditional 0:14:32.480 --> 0:14:37.040 Finish sauna, and I really wrestled over this when I 0:14:37.160 --> 0:14:39.280 was getting a sauna because I wanted an infra red 0:14:39.400 --> 0:14:45.880 barrel and I actually couldn't find any research to see 0:14:45.920 --> 0:14:48.520 whether they actually did it, so I did my own experiment. 0:14:49.360 --> 0:14:51.880 And what we know is that you need to increase 0:14:51.920 --> 0:14:55.960 your core body temperature by one degree in order to 0:14:56.000 --> 0:14:57.240 activate heat shock protein. 0:14:57.280 --> 0:14:59.000 So lots of studies have shown that. 0:15:01.240 --> 0:15:04.080 Being in there at seventy degrees on an infrared sauna 0:15:04.360 --> 0:15:07.800 for twenty minutes increase my core body temperature by more 0:15:07.840 --> 0:15:08.560 than one degree. 0:15:08.600 --> 0:15:10.480 Now, this is an an equals one study. 0:15:11.520 --> 0:15:13.000 If you're a little bit concerned if you've got an 0:15:13.000 --> 0:15:17.480 infrared SONA, certainly exercising beforehand and then getting into your 0:15:17.480 --> 0:15:21.400 infrared ZNA and then whacking up the heat that'll releasing 0:15:21.400 --> 0:15:24.920 those heat shot proteins. Other research has shown that a 0:15:25.040 --> 0:15:30.360 hot bath for about twenty minutes forty degrees centigrade hot bath, 0:15:30.400 --> 0:15:33.920 I'm not sure what that is in American money, must 0:15:33.960 --> 0:15:38.480 be around one hundred or so, but that activits heat 0:15:38.480 --> 0:15:43.440 shot proteins as well. Another thing that activits heat shot 0:15:43.560 --> 0:15:48.960 proteins and also cold shot proteins is cold water exposure. 0:15:50.520 --> 0:15:53.000 And it's really it's thinking about these things, right. So 0:15:53.040 --> 0:15:57.520 we know that exercise, heat exposure, and cold exposure in 0:15:57.800 --> 0:16:03.120 various different species all heat chock proteins and then they 0:16:03.320 --> 0:16:07.760 up regulate these protective mechanisms. So there's a number of 0:16:07.840 --> 0:16:10.440 things that we can do in terms of nutrition, in 0:16:10.520 --> 0:16:16.320 terms of supplements, exercise, hate exposure, and cold exposure to 0:16:16.360 --> 0:16:22.840 help to minimize this loss of proteostasis proteins running well. 0:16:23.320 --> 0:16:26.240 So that's it for this week, folks. Catch you next time, 0:16:26.240 --> 0:16:30.600 and just remember a strong body starts at the cellular level, 0:16:30.880 --> 0:16:31.600 See you next time.