Why Your Immune System Declines With Age | Dr. Max Krummel & Dr. Andrew Huberman

How the Immune System Develops

00:00I think most of us either remember or have observed that when humans are young, they get sick a lot more. Presumably, that's because their immune system isn't as well developed. But kids tend to get sick and then get over being sick pretty quickly.

00:16Yeah. Maybe you could describe what's going on there. Yeah. And it also is the case that you know as we get older much older in fact uh last quarter of life let's say people tend to get sick more uh what's going on um in terms of immune system function um or is there something more broadly happening at level of just kind of energetics mitochondrial function very curious about this if I can take a step even further back I'll ask you a question of like who are you and I don't mean that like in a personal sense, but I can talk about that too if you want.

00:50Uh, but the more the question is like at at some point where does your body end and where does the world outside start? And one of the things that, you know, you start to realize if you look in a microscope is that we're covered with microbes all over our surface.

01:02We're covered with microbes all the way in our gut. In fact, we can't, you know, you can't digest, you've probably heard this before, but you can't digest animal fats if it weren't for the bugs, the bacteria in your gut. They make some of the key components of of bile acids that allow you to digest animal fats.

01:17So, you need this system that's around you. So, you aren't just the cell like if you learn biology, you've got the again, we're going to go way back. There's the egg and the sperm and they fertilize and now you got this this this cell that starts to divide and gives rise to every other cell in our body.

01:32So you might say that your body is just that collection of cells, but in fact it's it's it's it's absorbed a lot of viruses and and bacteria from our environment. And you know, to go into that really briefly, that's really important because we only have 20,000 genes in our genome.

01:47So there's only so much in a given life that we can do with those genes. And so by absorbing all kinds of other species onto us, we get their genomes. So like you said, like I was saying, the the bacteria in your gut can now help you absorb nutrients that you wouldn't otherwise.

02:01If you eat sushi, you know, you've heard this probably, right? You get you get bacteria in your gut that can help you absorb the the the seaweed, you know, nutrients from seaweed. So, so taking this into your question, you know, when you're first born, you've never really seen anything.

02:15And so, two things are are I think worth pointing out at the early phase of life. One of them is for the first six months or so, your immune system is pretty poor at being trained on things. And it's presumably we presume that for those six six months that's because your body is developing so fast that if you were to have a super active immune system you might actually find yourself attacking yourself.

02:35You might think that you're foreign because some genes turn on during development and then all of a sudden you're you know your immune system's like oh I see something different and now I need to react. So that's well known and that's that's one of the reasons why some childhood vaccinations they're really important to protect kids in long over life.

02:51Why they aren't given until you're 6 months or or older. But I think to your point, one of the things that's happening with kids is that they then then as they go into their like until they're 10 and you're talking about they get sick a lot.

03:02They just haven't seen a lot of these bugs before. So they don't have an immune system that knows what flu is because they've never seen the body's never that body and kids body has never seen flu before. So every single virus and pathogen that hits it is going to elicit some you know some amount of illness.

03:18But then they have a very strong immune system. it reacts and you know gets rid of that with the exception of the ones that you know are those those certain viruses and bacteras mumps measles rebella that are they're lethal and that's why we immunize as we say and that's those are things that your immune system if they get too much of those kids will die and so it's better to protect them with a vaccine all right so that's the front end right the front end has this initial you know imunosuppression then just exposure to all these things that are in our environment and you and I take on as

03:48part of our genomes but we have to get a we have to reach a taunt with some of them. You know, we have to get to the point where the immune system can kind of like fire back when they show up if they're bad and and and allow them to live in us if they're good with us.

03:57And so I think that's what's happening a lot in those first years of life. And you know, you can see that both in the form of, you know, kids getting sick a lot, but you'll also see that their guts develop way diverse microbiome. You know, they allow a whole bunch of things that come in from the outside and are acceptable and are quite good for you.

04:16So that's the front end. In the back end of life, it's a little bit more complicated. But I'll tell you I'll tell you two things that I think are

Why Immune Function Declines With Age

04:21important. On the one hand is the idea that is is the fact that a lot of your cells in general become less functional including immune cells and you get less cells produced and and that might just be because you know we were never selected as organisms to live as long as we do right now.

04:35That's one idea of aging, right? We know that that we just were supposed to be dead by 70. Well, no, but we do know that that we can reproduce and and you know pass on our genes successfully already when we're 16. So you know the selective pressure to pass on your genes if you imagine that's how genetic evolution happens is that you pass on your genes as being successful.

04:54You can already do that at 16 and anything after that is just cream on the crop but um you know at some point maybe there's no selection. So we don't know that but it's it's a reasonable hypothesis to say there wasn't any real selective pressure for passing on genes that do anything past when you're actually having kids.

05:12The psychologists would tell us that uh the wisdom of people, you know, 60, 70, 80 and beyond is useful for um groups of humans that live in, you know, you know, villages of 100 or so people because they can give information to younger people that is on the periodicity of like every 5 to 10 years, maybe every 30 years.

05:34But that's a just so story, right? I mean, it's a nice just so story. I like it too. And the I think the genome geneticists will refer to that as like the grandfather effect where genes may be selected for and maybe they're mostly about you know genes that make us social in the in for for for the elderly that do you know they're going to have effects on the fitness of their grandchildren which is their genes.

05:56And so this yeah I think there's something to be said for that in in conceptual space. I don't know if I can prove it to you that that's a tough experiment to do. It's a really tough experience to have two villages where the you know the grandparents are eliminated or like kept you know both non-ethical and also non but we were talking about the aging

Cellular Mutations & Mosaicism

06:13immune system and I think I think there's two things that again come to this question that I was asking you like who are you um and I was saying okay well in aging you have this issue that the immune system is is tapering in its efficacy it's many of the cells that you you know you've been holding your whole life start to to literally they die off but there's another thing which is I think a lot of people don't realize when you say when basic biology ology say that sperm, you know, like uh fertilizes the egg.

06:36So, you've got your mom's genes and your dad's genes. You got 23 chromosomes for your mom, 23 chromosomes for your dad. And and and at least in when you're first born, every cell is a clone. It has exactly the same information. But DNA replication and and DNA sort of like fidelity isn't perfect.

06:51Like they say that on your skin, the cells of your skin may have somewhere between 10 and 30,000 mutations per cell per day just from like basic sun exposure. And it's that that's higher than some of the other organs. But the basic idea is that your DNA, you know, it's susceptible to UV radiation.

07:07That's one of the reasons we put on sunscreen. But what it what it practically means, no matter what number you put in there, whether it's 10,000 mutations per day or remember the the genomes are huge, right? So 10,000 mutations out of terabytes of of of information, still is only a certain number.

07:23But do that over every over years. And the main thing is that that means is that every cell in your body is no longer identical to the one next to it because this one got different mutations on day one. This one got some mutations on day two.

07:34And slowly but surely you are becoming like a mosaic. And I say mosaic, you know, because like the tile that you see in Morocco, you know, very intricate designs because if you actually, you know, start to look into tissue, you know, you'll find that certain clones, certain mutations do make certain cells more fit.

07:51And they're the ones that if you scratch yourself and a cell has to like some some new has to has to form, they might be the fittest to fill that void. And one of the other clones over here that got a different mutation may not be fit to fill that clone.

08:02And so you you end up with this pastiche of who you are. So now again I ask you like who are you now? So if I want to defend against something that looks different, what if everything looks different? What if every cell is different from every other cell?

08:17It's it's it okay. You want you want another analogy? I would like another analogy. The only um exception that I can think of to this and I could be wrong is that our neurons, our central nervous system neurons, our brain and spinal cord, most all of them are the same ones that we were born with.

08:36Same cells, but same cells, but so you're saying mutations are constantly occurring in the neurons in the DNA. So there it is fascinating by the way that neurons live that long. and you know hair cells that

How Stem Cells & Neurons Are Protected

08:45they say that the the proteins in in our hair hair cells of our ear are the same exact molecules atoms as we had when we were born. So there's there's some cells that are along the but in their nuclei the DNA that's encoding who they are who those cells are is subject to mutation ongoing and it depends on how deep they are like the we tend to think that one of the reasons that immune stem cells live in our bone marrows you know our long bones are hollow and in there is the source of the immune systems you know revitalization it's the stem cells that make more white blood cells we like

09:17to think that they live in there because it protects them from a reagent they they they they hang out you stem cells are You know that the bone actually serves not only a structural purpose in our body, but they it's a cavity in which things can live and keep it away from from solar radiation.

09:31Keep it away from chemical cues in the environment that can mutate. Sequester your stem cells and um don't burn them. Yeah. That kind of thing. Yeah. Likewise, the neurons in the in the uh inside of the skull. Yeah. And the spinal cord are protected.

09:46They're protected. Yeah. And that's interesting. Yeah. Yeah.