So what happens when you age? Two bad things in this category, number one, because of epigenetics, you are less likely to have trimethylation at histone three, so there's less things for these little grabber proteins to grab onto. Secondly, the HP one protein is less produced, so there's less grabbers. So because of these two things, your heterochromatin falls apart. So all of the bad things that I mentioned earlier are more likely to occur, right? The good news is we can actually fix a lot of this stuff, which is why I hate to always sound negative at the end. We fix it. But this, there's lots of models of aging, or theories of aging, and this one is called the blossom heterochromatin model of aging, and it's just one of a zillion. Okay, moving on, mitochondria. This is tenet two, and I promise the most of these tenets will not be as lengthy. So what happens to your mitochondria? Lots of bad things happen to your mitochondria. We're having this conversation at lunch. There are seven categories in which things go awry. Structure. Your mitochondria fall apart. The DNA falls apart. Mitochondrial dynamics. Your mitochondria fizz. They fusion, make more. That's mitochondrial biogenesis. You also recycle them. That's mitophagy. Your electron transport chain doesn't work as well because you don't make the sun units cardio stasis, just like in the rest of your cells, true in your mitochondria. You're sure two, ones, three, four and five live in your mitochondria. They fell over time, as well as micronutrient deficiencies in your mitochondria. The biggest one, of course, is NAD. Just as a random aside, I thought I would pick one bit of structure that most people are not familiar with. So again, everyone gets to learn something. This is the mitochondrial permeability transition core. If you are a true geek, you've heard of this. That's sort of a self identifying factor. So if you look at a mitochondria, I'm a geek, so it's okay. If you look at mitochondria, it is a standard organelle, right? And it has a lipid bilayer. The outer layer actually comes from our cells. The inner layer comes from a different type of cell, because we inherited mitochondria. We actually brought them in. We engulfed them many, many years ago. So the proteins or the lipids in the inner layer are different than the lipids in the outer layer. Anyway, inside, in the matrix, is where the toxic menu of all the biochemicals are from the Krebs cycle, pieces of subunits, et cetera, et cetera. And normally speaking, the inside of the mitochondria is separate than the rest of your cell. And it's separate for a good reason, because this stuff is toxic. It's like little nuclear reactors in there. There is, however, this pore, and this pore goes from the inside to the outside, and when you are young, it's nice and closed every now and then it sort of flickers, opens up every now and but we don't really know why. But in general, when you're alone, inside and outside are very well contained when you get older. However, this fails, it opens up a lot. We think, we don't know. We think that it's due to increase in free radicals and an increase in the calcium in the matrix of the mitochondria. But what happens when it opens bad things happen, right? So things that are supposed to the outside come in and vice versa. So fluid comes in and it causes edema in the mitochondria, and it destroys the electron transport chain, so you're not making energy as well. All the toxic stuff on the inside flows out, NAD flows up. The thigh ion flows out, and the most important thing that flows out is something called cytochrome c. This is part of your electron transport chain, and when it flows out to the rest of the cell, it's a signal for absolute cellular apoptosis. So if you can control this pore, you can actually control if a cell lives or dies under stress. And thanks to Leslie, I can tell you that spermidine is one of the agents that controls the support. So again, very important things to think about aging pathways 10 and three. I have four big pathways here. Obviously I'm not going to talk about all four. There are these seven millimeters, which we'll talk about in a second. There's the amp kinase pathway and the mTOR pathway. These are the pathways that measure how much energy you have and respond accordingly. And then I put the circadian pathways in there recently, because they control up to 40% of all of your genome. But we're just briefly going to talk about sirtuins. Sirtuins are histone deacetylase agents. Not that anyone really needs to know that, but what they do do is they control all cellular homeostasis. They are shortened around the cell. One, six and seven live in the nucleus, 345, as I said, live in the mitochondria. You start becoming sirtuin deficient by the time you're 43 is actually a little bit sooner they think that we start losing that by the time you're 35 this is when real agent kicks in. This is my laundry list of things that they do, and the list is just infinitely long. So I took the big ones so they sense energy. They monitor your metabolism, telomerase activity, gene expression, blah blah blah circadian rhythms is huge. In this one, people always say, why can't I sleep? And you go to sleep, experts and like, oh, turn your light off. You know, don't look at your computer. Blah, blah, blah, blah, blah, Oh, no. This is all biochemical. You make two proteins that turn on and two proteins that turn off sleep. And if you don't make those, I don't care how many, like blue lights you have on or off. You're not sleeping. Life is biochemical, okay, but we're going to focus quickly on sir. Two and 713, and six, historically, are associated with longevity. Seven is my new pet project, because it's associated with heterochromatin that I obsessed about a few minutes ago. It lives in the nucleus and the nucleolus the only one that does that, and it does two important things for your DNA. Number one, it actually tethers the heterochromatin to the nuclear envelope, so it maintains nuclear structure, and it also organizes DNA repair mechanisms. And with all of the other ones, it declines with age. It's NAD dependent. So you really need to think about, when you create your protocol, worrying about sirtuin seven, tenant four, quality control. This is the idea that you have a factory. Things are broken, you must fix them. So this is DNA repair mechanisms. This is proteostasis, and this is autophagy. I'm just going to talk a brief minute here about DNA repair mechanisms because every day, every cell, you have 10 to the fifth errors. Think about that, 10 to the fifth errors per cell per day, that is a ton Your body knows this. It's pretty smart. So it has two major mechanisms to fix single stranded errors and two major mechanisms for double stranded and then there's mismatches of sort of its own category, right? But these mechanisms, of course, fail with age. You have more DNA damage. With age, without more likelihood of sene cancer, of the single stranded base excision is more common, but nucleotide is the one I wanted to just briefly mention, because this is why you get skin cancer. UV radiation literally melts your DNA together, specifically the thymine residues. That's not the point. It melted together in something called cyclobutane dimers, and you could measure this. So people say, how much time you spend in the sun, like not a whole lot. The good news is there are drugs and chemicals that you can repair this faster, and you can reduce the incidence of it, not just lotions and such. There's actually biochemicals you can put in your body, and that's part of the protocol. But the important thing is to know what you what you're getting when you're out in the sun. Okay? Immune System. This is 10 at five. We're just going to do this really briefly, because I could talk about this one for absolute hours. Your immune system does two essential things, and it does it via two different mechanisms, right? You've got your innate and your adaptive mechanisms. What's important is what it does, does all of two things. One, it protects you from the outside world, and two, it monitors and gets rid of your own cells that have gone awry. That's it. That's all it does. So when it doesn't work, what happens? Number one, ignore the fact that that's not completely blended. Number one, you're more likely to get disease if you can't fight infection, right? That's it's a primary job. You're going to have more infections. And we see this. People in nursing homes are always getting urinary tract infections or pneumonia or et cetera. Two, increased risk of malignancy. Why? Because your job is to clean out your bad cells. If you can't clean them out, you're going to get cancer. That's just what happens. Three all the infections that you have in your body, they're sort of tucked away. The latent infections are going to be reactivated, tuberculosis, shingles, all of those things. They come back because you can't control them anymore. And maybe the most important, while. This is systemic inflammation. We all know that this becomes inflammation over time that leads again to cancer, cellular dysfunction, blah, blah, blah, blah, blah,