Alzheimer’s Disease: What We Know, What We Don’t Know

Medical disclaimer, please note that the information shared on this podcast is for educational and informational purposes only and should not be considered medical advice. Always consult with your healthcare provider before making any changes to your health regimen, including starting new therapies, supplements or treatments. While we discuss cutting edge research and advancements in cellular medicine, individual health needs vary and professional guidance is essential. By listening to this podcast, you acknowledge that neither Dr. Seeds nor the podcast team is providing personalized medical recommendations. On today's episode of Redox Revolution, we're going to revolutionize the way you look at Alzheimer's disease. [Music] Welcome to another episode of Redox Revolution, and yes, I am here with the infamous Matt and Mattie. I don't know what makes me infamous. I think me and the audience would both agree that the less I talk and the more you dive down your rabbit holes the better. We need you to chime in to get them back on track. I'm just excited to be here with both of you and to be able to avoid, I get better at avoiding your hidden tactics and how you guys like to just tear at me where you can't do that. Well, you know what, fine. You know what? Let's just address the elephant in the room then. Why is your shirt doing that? I don't know. I got back from skiing. [Laughter] You know, I've gone through that body partitioning phase of improving more lean mass. I don't know. It's embarrassing, but let's go. All right. You should relax though. Today's topic is actually a little bit of a heavy one. Whoa! So kind of a little bit of a gradually in it. Heavy, or just heavy? Just a heavy topic. So an estimate of about 7.2 million Americans age 65 and older are living with Alzheimer's dementia. That translates to about, you know, 1 in 9, about 11% of people over 65, with nearly 2/3 of those affected being women. So for years, scientists and clearly researched dollars, they've focused on things like, I'm going to mispronounce this, tau tangles. I think you pronounce that pretty right. All right. Cool. And plaque build up as the cause of Alzheimer's. So continuing the Alzheimer's research discussion and where we are currently is the topic of today. So how has that view changed? Where has all of that research gone and where's the research pointed currently? I feel like it's more universal now. They're not just singling out women as much as they used to. But also, I feel like what you've emphasized is how they're really showing that before you even start developing symptoms, that neurocognitive disease process can be starting like 10 years in advance of that. That's really interesting. You bring up, they're not just focusing on women because that seems like the inverse of something we've discussed before, which is a lot of protocols are built around men and women tend to get ignored. So are you implying that it's kind of the opposite here, especially with 2/3 of it being women, most of the research has been on women? I feel like this is just one of the topics that I don't hear as much focus on women. And it might just be what I'm reading or listening to. I'm just enjoying listening to this conversation going back and forth here right now. Well, as great as Maddie is and as great as you or Maddie might think I am, no one came here to listen to us. So Dr. Seats, why don't you chime in on the conversation? Gosh, well with what Maddie was saying, it took me down like, I went down three rabbit holes immediately and I forgot the whole. Wait, while he's remembering, there's times consultations where the patients there to definitely talk to him not to talk to Grace Jake or myself and he's just sitting there and we chime in. But then he just keeps sitting there and we're like, I'll text him and say, speak. Because I'm thinking you get lost in the, you get lost in the thought. Lost in the sauce. Lost in the sauce. The sauce. The sauce. Well, okay. Here is, you know, I continue when we go into these themes of anything we're discussing. I try to always emphasize why cell hearing medicines, the future of thinking and why it's so pivotal in how we look, how we revisit disease. So how this is an example of this, this is, all simers, let's talk about it's related to dementia, cognitive dysfunction, loss of what people see as memory and decision making and they see a decline in mental status. And they're different degrees. But the focus has always kind of been on the neuron. It's like a one, it's a one phase disease. It's neuronal injury with plaque buildup. You just talked about amyla beta and towel plaque. That's kind of been this, in this place for the last, I don't know, 30 years or so of this, this focus. And what I'm going to tell you is, and what I, what I think is absolutely undeniably true is that we can actually, we could look at, at all time, or at that process of of calling Alzheimer's a phenotype, meaning, okay, this is the end process. It's a phenotype and there's many upstream cellular failures or inefficiencies that lead to Alzheimer's. Not this plaque, amyla beta, it's not towel protein. It goes much farther into being able to actually look at this again as a phenotype that means it's correctable, but that there are many triggers that can, that push all together into this process. And that's why this is such a difficult disease to understand because it does happen over 10, 20 years, and what happened, what we're, what I believe is the critical thinking here is understanding that there's, there's a, that there's an energy, there's an energy failure, there's, there's a mitochondrial influence, there's an immune influence, just as we've talked about before, there's a vascular influence. So I have five categories right here and your name and some of them, I think we should go through them one by one, but let's start with just listing out the five. I haven't even, I haven't even finished my, oh yeah, no, your name on them and I just want to make sure we're building through five as he adds detail to it. I have faith. So if we're talking about all the causal factors, just based on things that you've said in the past, the five that we kind of have it broken down into is that first would be this amyloid accumulation and towel pathology, which you've kind of touched on. And this is in no particular order. Number two, being the microglial dysfunction and neural inflammation. Number three, being mitochondrial dysfunction, aka your energy crisis. Three powerhouses of the cell. Number four, three out of three. Number four vascular disorder. Four out of four. And number five metabolic dysfunction, i.e. insulin resistance, quote unquote type three diabetes. Yeah. So real quick, just to tie up the loop on this first one, the amyloid accumulation and towel pathology. How does that factor into it? And then we'll keep moving along the chain here. Well, I know I'm trying. Yeah. So, so that is so that that's a trigger. So we were focused on neuronal death and we were focused on, hey, it's this plaque formation. And hey, we're going to make these antibodies that are going to go in and eat up this plaque and take it out and we're going to we're going to correct everything for everybody. And guess what? We did it. We did it. And because we realize that that's a it's an influencer on the the neuron. And I'll go into a little more detail on that because I think it's I think we need to do that. If you'll let me the it's an influence and and and that means there have to be if that doesn't take care of the problem. Then there have to be higher mechanisms that are influencing this problem with with with plaque and other issues. So let's look at that. Let's let's break that down and say, OK, well, is there something is is amyloid plaque. Is there a reason that it builds up number one and are there different types of amyloid plaque. I bet yes and yes. The answer is yes and yes. It's it's related to so so think of this as I look at amyloid plaque and tile plaque as these are protein. This is a proteostasis issue where we're losing the ability to maintain proteins and proper folding of proteins and amyloid is no different amyloid is in it's it's in the mitochondria where you have these amyloid precursor proteins these app's that start out that have to be cleaved. And for the audience cleaved. You have to be you have to cut them into appropriate length amyloid segments and and so there are these secret cases that do that that cut them that they're like scissors and and typically in healthy amyloid and not inappropriate amyloid it's it's an alpha secret taste that does that well. In in this disrupted amyloid beta type of segments it's a it's a beta secret secret and a gamma secretace and the question is well then what influences that well it's oxidative stress. It's an energy problem that happens in the the mitochondria of losing efficiencies in the mitochondria is we've always talked about in this oxidative phosphorylation that that produces ATP and NAD there's a disruption and there's this oxidative stress and that oxidative stress then influences the the secret cases that go wrong and then you have this in appropriate amount of amyloid that builds up. And it's it's amyloid that can't be removed so so when you have oxidative stresses in the mitochondria. They also influence something called atophagy in the cell and atophagy is about cleaning up debris cleaning up bad players and then letting the cell repurpose itself to still do its job. And so you lose that atophagy of cleaning up doing its own job. You lose also the efficiencies of what's called the proteo zone which is ubiquitous in proteo zone it's how we remove proteins like like you can clean you can clean them up. And still salvage some amino acids or you can totally remove a protein and that's called ubiquitonation it's a. It's on this topic I promise Jesus Christ I was on a roll. You've a donation you've a donation but since this is all happening in the mitochondria and you lose atophagy are you losing my top. Yeah, yeah, okay, so that's another so my topogy is another there's a topogy cleaning inside the cell and then there's my topogy removing bad mitochondria or other things that we can do with that are more complex but removing mitochondria that are bad players or removing the the inefficient mitochondria. So that's my topogy so but that's influenced by this also you have a topogy my topogy that are disrupted so you lose this control of maintaining the environment that's that's appropriate and this is in the neuron so the mitochondria in the neuron and this is like it's is happening in the neuron so the neuron then loses its calcium metabolism goes through apoptosis meaning it blows up or it's a. An anonymous destruction so so that's what can happen from from emily beta in the neuron will then towel is another type it's a micro tubular protein that is very important in the axones where axones are what are between neurons that are that are transmitting the the messaging and short long story short might Condria travel in these axons they travel to because energy that's a high energy state you need might a condria well if these if this particular type of tubulin Protein which is towel it what happens with oxidative stress is we lose we lose the ability to control well, let me say this I'm sorry. I know I'm getting deep in this but this is this is a hyper phosphatation process hyper where there's too much hyper phosphatation phosphorylation and so this towel is phosphorylated and then it it It misfolds and it becomes tangled in the axon so you lose This energy that's being transported you lose connectivity and that's the early decline of how Your brain is working. It's losing you you lose connectivity before you lose the neuron So there's there's this towel influence. There's that Amoled beta influence and this is just loss of proteostasis which is all related to an energy crisis From the mitochondria that has influenced all I've just gone through how that's influenced because you increase in hyper phosphorylation occurs with oxidative stress so So those are just that's a small component of Of course and when I ask you each of these five obviously they're going to dive into each other It makes a circle. It's not five different lines, but I like this I like this approach of us Taking them on one by one and then they continue to cross weave into each other. So you touched on let me finish but okay We since he and I can I ask one quick question since you interrupted him first. Yeah, do does the When the proteins get or when they get tangled is it just a slower process or is it just like completely stopped the signal? It's a slow it's a build up. So it's a slow process. This is why This is why this can be this low inflammatory oxidative stress that happens over years 10 20 years this is This is one component of an energy crisis that affects the neuron and the axon We're gonna enter into other areas here in a second that are also having an influence in the brain think of all of these as triggers that are all coming together to it's why there's no one super drug where everybody thinks there's one thing you can take and you're gonna make the brain better. It's like Not gonna happen. Yeah, you you need to understand these processes because that's what we do in cellular medicine We go after all these individual areas. So so that's one area is this loss of proteostasis secondary to in We call it bioinerjics or energetics and energetics is is about the cells a capability of What happens with energy and how it? Produces energy how it regulates it and how it distributes that in order for the cell to repair itself control membrane stability and Signaling and effects it affects energy to right well, that's energy That's eight that's the beginning. That's what I said all right. We started from starting point number one Uh-huh now let's do this all over again. Okay start from starting point number two. Yeah microglial dysfunction and neuro inflammation you started to touch a ton on it, but let's just start from there this time Okay, so the next we're kind of phasing this now into immune problems which are microglial cells and also we consider astro sites as my as other glial cells, but in particular The microglial cells and immune cell that now can change Where the microglial cells job is kind of like what we talked about autophagy in the brain. It's there to clean up debris It prunes the synapses those axons and those it it it's there to In the brain to clean up debris Let things keep remodeling as far synapses. It's it's it's it's pruning right it's like pruning with So it's a good player. Yeah, and and phagycytosis just removing debris and and keeping the environment correct well it all of a sudden the immune activation part it changes into going from a structural control That is necessary to control the environment for that neuron to do its best job and the astro site it It now turns into this inflammatory producing cell that makes cytokines and chemokines prote these inflammatory mediators that Lead to oxidative stress in the neuron oxidative stress in the astro site because Real quickly the astro site helps the neuron with energy and we won't get into that but the astro site is very important for making up and using Converting lactate Into glucose for the neuron. It's a secondary mechanism of producing energy for the neuron So overall what happens is with this immune activation now we've introduced another component of how the neuron now is is exposed to more oxidative stress Which is bad and so the the microglial cells importance is now it's it's switched into into this inflammatory immune cell that increases oxidative stress in the neuron also in the astro site and And this is another disruption now of another stressor on the neuron that leads to loss of resilience of The ability of the neuron to handle stress Fragility again, okay, but there's a component also that we have to understand is is actually the mitochondria in that microglial cell it changes its metabolism and Into more of a glycolytic state because that's easier right not a not not an oxidative phosphorylation state that leads to inflammatory changes in the microglial cell so again energy bio and energetics mitochondria are playing a role here in the immune This is perfect. Don't Keep rolling because number three was mitochondrial dysfunction in the energy crisis so keep on zone with the mitochondria Whoa, yeah, this is I like this flow. Oh my question fits here. It's help them. Can I answer the mitochondria? The mitochondria switches to the glycolytic because that's easier right like patholist resistance in a way Yes, because it makes it makes ATP fast It's it's kind of it's kind of turned into an mTOR state where it needs fast energy and Yeah, that's kind of what have it's I guess that's easiest way to say it and she just blew what What you asked me oh mitochondria you wouldn't do it so we're starting from driveway number three. Yeah, so might so the mitochondria mitochondrial stress here is a big is this I think is the elephant in the room that I was gonna say the same thing Shmeiden That this and nobody will get that but this is the So the mitochondria goes through inefficiency of where it needs to be remember We talked about mitochondria need to be flexible in handling energy substrates meaning glucose amino acids and fatty acids so When mitochondria loses its efficiency to manage that it Becomes more it creates When we lose fat oxidation we lose the ability to Control oxidative stress. So we lose redox in the cell. So this is all where redox comes into play redox disruption is what's occurring and that leads to poor signaling Because remember mitochondria signal and they have incredible signaling properties that influence immune cells influence other other cells in the other other organelles in the site apply in the cell itself So it just it's mitochondrial inefficiency then that leads to this mismatch of Energy ATP and NAD that That can then change this this game as if redox is then influenced and And abnormal That's where you get into this loss of these nuclear cofactors like NADPH which which is very important in keeping Oxidation under control, but just as important in producing neurotransmitters Your dopamine your Serotonin Your phenylalanine your your gab yet everything because Your tiresome hydroxylases your phenylalan hydroxylases your Your trip to fan hydroxylases those are all They need NADPH from the mitochondria to do that so so here you have all the sudden introduced this Molecular mechanism now to understand better and you lose the out you also lose nitric oxide which is very important and that'll be something we'll get into in the vascular part but These are essential for what the neurotransmitters The vascular issue we'll talk about in a second So here's another part of the brain Because of redox because of loss of mitochondrial inefficiency again energy And it's it has an overall effect and and though and remember mitochondria are in every cell here They're the powerhouse of the cell. Yeah, so it's it's fascinating right when you start to think about this and and how There's further upstream players and and it's so I Don't know if I can say this I've had a lot of criticism outside from very very well respected Players in the field of Cognitive dysfunction all simers and Brain disease through neurologist who've questioned hey Bill you're missing it. It's it's this and it's the immune system. It's the It's vascular. It's it's like well of course it is but Don't you want to know why those things go wrong? Yeah, you're not denying that it's not those things never It's but it again. This is the power of understanding molecular pathways and mechanisms of how you can go back and relay it to the bio The bioenergy The bioenergy set lead to redox and bat to redox imbalance that lead to immune just regulation that then lead to vascular compromise that then lead then love a good bridge then lead to Proteus stasis loss of proteus stasis. So there you go. I just connected it always let's back up to vascular back into the driveway Approaching it now from number four. I love it. That one came to a great head now. That's approaching from the fourth pathway this vascular disorder Well, I mean so so this is This is where we start talking about You you get into so this is where vascular poor perfusion to the brain is also a contributor to this metabolic or to dementia and You can back up into that by saying okay, well, you know what typically leads what what's the most common problem that that involves Vascular brain. It's high blood pressure and From a 30,000 foot view, but what's involved with the potential of that is that it can lead to Even though it's high pressure it can lead to hypop perfusion of the brain because it can damage These this high pressure can have an effect on damaging the endothelial cells of the small vessels and you get small vessel disease you get You get endothelial disruption that That leads to inflammatory changes now in this vascular perfusion and and again that That is related to mitochondrial issues within the endothelial cells themselves and it all has to do with What is one of the things like I said nitric oxide production loss of the vasodilitation But what what's even more significant is this is where you start getting breakdown of the blood brain barrier and So that's where more immune issues can be a problem toxins Lipopodosaccharides things from the gut we were talking about that can get to the brain a lot of things start changing and You also get this You get Into problems with what we call glinfatic drainage. That's when all the toxins drain from your brain Correct, that's when all the met whether we call them talk that people call them toxins But they're metabolites and things that have to be removed and so glinfatic drainage is affected so this is big and and This has everything to do now with imagine with that aspect having an influence Do you think that increases oxidative stress on neurons and and the glial cells and could lead to more immune activation? absolutely and lead to Bioinergic issues also so can that feed that process? Yes, so here's another area that overall mitochondrial or energy deficiencies or might a energy crises can be a significant component and and I Think this is where I think from the vascular standpoint Because we understand so much about high blood pressure and how that can influence what we would call early or mild cognitive impairment You know you you have This may bring me into an area to just discuss real quickly with with neurodegenerative disease You have a finite time of where you can really make some changes in that phenotype I talked about you know This is one of those Things that influences the phenotype is it's high blood pressure It's why we get on this early because it over time It's a one of those factors that leads to the mild cognitive impairment and we know so when we've talked in the past about studies that Validate treatment and so forth we know that if we treat high blood pressure we can we can mitigate To some degree or even complete improve mild cognitive impairment if we catch it early on with this blood pressure issue so it's why everybody should pay attention to that Because that actually leads to something over time and and it's it's these time things it because the brain is Incredible and can and can have all these different triggers going wrong and can still function and It's a it's how the combination of all these things over time lead to that Demise when you see somebody that really has Loss of cognitive function. It's why it's much harder to reverse that because you've got all these triggers that are in play of what I've just gone through So you got a lot that you have to fix but if it's early on like like a Something that can be easily identified as not a biomarker, but blood pressure That's pretty cool. I mean you can get on that quickly and so that has a big impact From from the vascular side all right path number five unless you had a quick question. I did have a quick question Oh my god So like just how blood pressure can't what about diabetes? Oh Okay, so pathway number five metabolic dysfunction i.e. insulin resistance type three diabetes. Oh I hate and people say this type three That's why I just said diabetes Yeah, general. I gotta bring it in from any angle that anyone's ever heard, but yeah, well, this is metabolism now. Yep, so the so you've so you've hit all the things I said Just putting it in a structure so that we can easily follow it and knock them down one by one Keep you on even though they all overlap and it's not like these things are siloed, but now let's approach it from The last driveway you must go to my masterminds. I must run your masterminds Doesn't necessarily mean you listen to my masterminds, but okay um So metabolism so this is where metabolism is this other trigger or influencer of potential energy crisis let's say I think I like maybe the that sounds nice for the house hide meres or dementia Well, yeah, maybe then maybe the um Maybe my approach might be better with this particular neurologist if I said energy crisis is supposed to might a congria. I don't know with the So so here's where metabolism comes into play because what is the neuron is glucose dependent? All right, it needs glucose Uh, and it's very it's so glucose plays such a significant role uh in Managing energy because it needs it fast the brain is you know is is Requires a tremendous amount of energy so by going through glycolysis You're going to be able to meet the needs of the brain when it When it fires to to get that The signaling everything that needs to be done through glycolysis through glucose And it's glucose dependent and it also has this secondary mechanism Of or process of where the astro site can contribute glucose as the needs or demand rise that Astro site can convert lactate to glucose for the neuron um to meet the stresses and stressors and so So if that goes so and and what is that dependent on um the neurons dependent on insulin to to bring glucose into the neuron and um and convert it into energy through glycolysis So in insulin resistance the neuron then has a it's It becomes inefficient in not being able to provide that energy well When that starts that's when the astro site starts to try to make up with lactate Converting to glucose and it does a good job for a while, but then that's over That can be overwhelmed and and so when that happens if we're not making enough energy And we're pushing this system. We're we're creating again this process of of oxidative stress in the neuron That leads to calcium dysregulation in the neuron that then leads to um apoptosis or or loss of neuron neurons or or inefficiencies of the neuron not being able to to work efficiently meaning You know cognitive problems so I had So just using glucose isn't a bad thing As long as everything's working efficiently, but when it's Using just glucose and not working efficiently that's when you can have the buildup of like the reactive oxygen or oxidative stress So when it's losing it's a built when the neuron is not able to To like a muscle cell to take in glucose Well, then it's being stressed, right? And it doesn't have that So it doesn't have that capability It has might a condry in it to use oxidative phosphorylation, you know to make energy also ATP, but it's not That the the neuron needs a lot of ATP and and it needs it now and it's that's why that that's you know That's why glycolysis is so important because of its It's quick turnover to ATP and NAD And so it can never meet those efficiencies and there's no real uh The the sort the fatty acid source isn't there Like this glucose sources for the brain. So that's why ketone esters are so important That's why ketone esters can be a work around and endogenously Um or through ketogenic diets why you so in and that's a great thing to bring up It's why it's how you can work around a problem of insulin resistance or inefficiency of getting glucose ketones can be absorbed um through the blood bearing barrier and can be utilized by the mitochondria immediately without sacrificing too too much energy to make ATP and NAD. It's why you can see uh really unique and in interesting acute changes in mild cognitive uh problems where people can they they very quickly regain cognitive abilities. Yeah, it's a and again, it's a timing factor when you catch that and it's um That's a whole nother podcast podcast, but it's uh you you brought up something very relevant and very useful for people to to kind of comprehend and understand how these substrates if you know how effective they can be and you know when there's certain issues you can bypass genetic issues um uh Because remember when you have these oxidative stresses that occur you're also getting membrane stability broken down which we've talked about before membranes barriers uh breakdowns that membrane stability is very important in in neurons and um and the other uh the astrocytes and microgridle cells and so forth. So it's it's hard to be reductive here but if you'll allow me to kind of go through three statements and then ask the precluding question. You know starting in mastermind 14 and then again today you've really set the table with how important it is to focus on this energy crisis and how it might underpin a lot of these other things that while they're just as important um this mitochondrial attention is something that just can't be ignored. You've discussed how this doesn't just take place overnight that all of this stuff is intrinsic and related to not related to but intrinsic to aging. How you can start to try to measure some things like the one example i remember you given right now was the hypertension where it's like hey pay attention to this because over years this is going to be something that's going to come back a little bit later um it's one of those triggers yeah and so my third point here being is coming back to one of the very first things you said this Alzheimer's dementia really being a expressed phenotype. So where does this he was listening yeah i i think that isn't that i think that's kind of cool though if you think of it as a phenotype and what influences phenotype many many different stressors um and and we've we've indicated these energy they're all energy dependent stressors and so that takes me back to oh boy if i look at this is uh my question was where are we now so there we go go ahead keep going okay we're we're right back at cellular medicine and cellular medicine can truly define this this process of well how does this phenotype how is this created well it's created by number one uh an issue that happens with the bioinergetics the bio what i said of how the cell is able to generate energy distribute energy regulate it and then what happens with that energy as far as maintaining repair or membrane control or signaling well when that goes wrong what is that lead to it leads to immune dysregulation it leads to um it leads to um what we say immune dysregulation it well it leads to redox issues then immune dysregulation then vascular issues can can potentially be part of that and and then proteostasis issues and they all all work in in this trajectory of all having influences are being influenced by mitochondria because that's kind of the the mitochondria is the key to those energy issues energy crisis so it come it's why it's why health is just uh it's i don't know protocol yeah and i i think people are you know when we look at this recognition of hey why is this happening why are we seeing more of this today than we saw maybe earlier well yeah people are people are living longer um and and here's here's a perfect example where longevity doesn't equal health span it is a perfect example of this it's like yeah people are living longer but they're losing their their cognitive skills is that what you want is that longevity no you want a health span go ahead i wanted to go back to like your question that you had started with with like more research and like the female population the male and how i was like i don't think that's prevalent i actually feel like what it is is i feel like that's not as prevalent just because we day to day just focus on the pathways and different ways that can lead to cognitive function not so much who it is just more of the pathway and science which is the same why is two thirds of a woman is there a is it hormone resource oh yeah it's a it's that complete men stress it's that complete miss miss uh inappropriate miss conduct of our medical groups totally putting women 30 years behind with with the understanding of how important estrogen and progesterone and testosterone are in in this bioinergic issue that we talked about i mean oh so you're saying it's an inorganic distribution you're saying it's been caused hell yeah we've ignored it we've we've made huge mistakes that have cost the female population um uh we can't make it up i mean we we really fucked up and it's all and we've proven that and it's becoming full soon enough it'll come full circle when everybody gets educated enough to understand this and it's just coming out now the black box warning was removed correct yeah well that was for yeah yeah for actually it's going to be all hormonal uh hormone uh hormones play a role yeah but this also goes back to hormones go back to mitochondria but but for females in particular it's a it's a way you can look at it very simply it's a disservice that's happened and it it's why over time you know when you go when women go through menopause that's kind of as they're getting into premenopausal menopausal puzzle places are uh changes that's where you start seeing the the incremental things that can start building up uh over time with um with this bioinergetics because of the the hormonal issues and that change which we can we can absolutely influence today and we were before but we were bastardized for it and we were told we didn't know what we were talking about if we were told we were we were bullied but but some of us weren't bullied because we knew the mechanisms and and no one could refute it and you talked even these experts who were even wrote the pay okay I should say we're good this is a it's been a media episode and not to make it media but I want to break the performance protocol into three questions you're really challenging him today with these no but I think this is important um the three parts of the performance protocol being like what can be monitored what can be done and what can be further researched so what can be monitored if we had a performance protocol because you brought up the hypertension and that one has just stuck with me what are some of the things as people continue to age just some key metrics to just be watching to just be like take care of yourself to keep an eye on well just remember I mean we spent a whole episode on this on on the gut I mean you know when you start having gut issues that should be set off some alarms that that can have a influence on the brain right um sleep disorders you know if you're not sleeping well can that influence absolutely if you're not exercising if you question yourself well that have an influence absolutely what about stress stress is is a great that's a that's a whole another podcast that we've touched on individually through different podcasts where where stress is this is this other trigger um it's in it's another trigger that affects that phenotype through a way that we now we now can classify stress as what it does to um to create these damage associated molecular patterns that are that are made in in the cell that lead to immune activation inflammatory changes oxidative stress and this and this loss of redox and this whole process about a kind of inefficiencies and so forth so it's definable it's it's it's again it's knowledge that we can't ignore and it's all coming together now and and that's what's beautiful is that people want to learn it people want to understand it but what's even more intimidating I think for the physicians is that the patients want to know now number two good good that no no that's a perfect bridge yeah you just you just that was a moment that was like if I could drop this mic I would drop it that's a perfect bridge so the second part of the protocol is what can be done so let's say patients are noticing some of these things slipping they're having deficiencies one of the endogenous options you just brought up with ketones is so that's diet so that's substrate diet related right can you yeah can you improve the efficiencies of cell function the bioinergic let's say energetics and urges how everyone say can you do it through which we eat absolutely it's it's getting this flexibility back into the cell and into the mitochondria by utilizing carbohydrates and proteins and fatty acids appropriately well a super group a super food group we could look at is ketone asters and either either through a ketogenic diet which that gets a little more complicated because ketogenic diets can be very unhealthy people can be a tremendous benefit for a finite period of time because you can get into some immune issues if you do it too long over three or four months it's it's a good thing to rotate through but this is where all like if you go back and look at all the data on the Mediterranean diet it has real implications of showing how it improves these things we've discussed about metabolism and and energy and can improve or can protect people because of the fats and the right proteins and the carbohydrates and fiber it can protect people and the from those triggers of changing the bioinergic that lead to neurocognitive dysfunction so diet exercise sleep so I'm that I can we'll do number three and I feel like I'm seeing a common theme and and then and then we could even you know then we can go this is where we take the we take that next level of okay well gosh then as we age we do we have certain genetic predispositions that potentially can work we haven't even gotten into that part of SNPs single nucleotide polymorphisms of of genes of how that can affect if the environment's not right it can flip those and can that be an indicator to push this process in the wrong direction yeah and and then we can get into well are there ways to mitigate or help these cells you know with certain supplements besides just food groups or particular peptides or small molecules and that's where it gets into the intricacies of really understanding southern medicine and and molecular pathways where you can you can really work to the advantage of improving health span that will have an influence on this when you're trying to intervene with mild cognitive inefficiencies that are already starting and three and you may not even see them the third performance protocol the third part of our performance protocol today yeah is um you know the first two parts being what can you watch out for what can you maybe do about it when the things you're watching out for either aren't working or you can't watch out for them and then what can we do about it here in the future so this third one is kind of for the research community you know if you'd a blank check and you could just grant a lab something to look into is there anything in particular you're like this is something that I'd love to see studied and you can be as finite in my new ears you want to be but I'm just curious like where would you put like specific to this yeah where would you put research dollars next like what's your next big question uh it's not that one one drug or one uh new molecule or or even one peptide is going to make the difference it's it's invest in that this this team of people that are looking at all these influences together and work on them together like from a perspective of I would invest in a group of people from cellular medicine like kind of controlling the the thought process of you know microbi people in the microbiome area people in the in the stem cell research people in and exosomes people in the in genetics in in looking at the genome the transcriptome the proteome the metabolism and and together approaching this process that's that's what I'm always trying to capture when I'm when I'm when I'm lecturing I bring all of those pieces into play for people to consider of how important that is nobody's doing that no one's doing that and if you had the money to invest in a group like that where you've got a thought leader that pushes all of those people in one direction watch out interesting so kind of gave me a non-answer but I get your answer instead of like an interesting one thing to look into more basically what you just said is you don't like this siloed approach to the research you're never going to get anywhere go ahead many so how you went through like there's five areas that can all I could make it more but yeah we'll just gonna focus on the five now is it kind of a like what came first the chicken or the egg or is it just a anything could drive it but it all ends up at the same cell your medicine drives all of it and it's how we can all talk together because you know that I know some things but there are people that in the microbiome world who have far more knowledge than I do people in the stem cell world have far more knowledge but I myself and others could help direct the conversation or the the processes of where we it's like building the atom bomb right I mean bad example to use but remember how Oppenheimer put all of these people together to solve a problem they were all experts in different areas of hauling the desert together and they didn't leave till they figured it out yeah I'm not getting I'm using that as an example but that's that's how shit gets done it's like teamwork it's total teamwork mix the dream work it whoa I've never heard that no that's like one you have to deflate could have could have been my win for the day now you get the mitochondria is the powerhouse of the cell and he's enthused enough about that without it really hurt it it and two of these and part of that too though right what part of that is every you got everyone has to drop their egos yes yeah even even the person like myself who may think they're in charge sometimes doesn't fit out the door yeah drop the egos and I think it's about time to drop this episode yeah was that a good that was great was that that was that was that's true that's truly what has to happen and I'm I'm just gonna say there are these think tanks that are out there and all this but that doesn't happen it doesn't happen like I'm taught what I'm saying needs to happen and it will happen I'm telling you it's gonna happen because um patients want to know yeah and and this the more the more that cellular medicine is understood the more that people get on this bandwagon or platform and get smarter holy smokes like I said lots a lot of people out there way smarter that are gonna make more sense out of this and push push that process mad maddie thank you for another episode of uh Redox Revolution um until next time