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

Huberman Lab Clips09:57Added Aug 31, 2026

Dr. Matthew (Max) Krummel and Dr. Andrew Huberman discuss how the human immune system evolves across the lifespan, focusing on early immune development, the ...

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  1. How the Immune System Develops

  2. 00:00I think most of us either remember or
  3. 00:02have observed that when humans are
  4. 00:05young, they get sick a lot more.
  5. 00:08Presumably, that's because their immune
  6. 00:10system isn't as well developed. But
  7. 00:13kids tend to get sick and then get over
  8. 00:15being sick pretty quickly.
  9. 00:16Yeah.
  10. 00:17Maybe you could describe what's going on
  11. 00:18there.
  12. 00:19Yeah. And it also is the case that you
  13. 00:22know as we get older much older in fact
  14. 00:26uh last quarter of life let's say people
  15. 00:29tend to get sick more uh what's going on
  16. 00:32um in terms of immune system function um
  17. 00:36or is there something more broadly
  18. 00:37happening at level of just kind of
  19. 00:39energetics mitochondrial function very
  20. 00:41curious about this
  21. 00:42if I can take a step even further back
  22. 00:45I'll ask you a question of like who are
  23. 00:47you and I don't mean that like in a
  24. 00:49personal sense, but I can talk about
  25. 00:50that too if you want. Uh, but the more
  26. 00:52the question is like at at some point
  27. 00:54where does your body end and where does
  28. 00:56the world outside start?
  29. 00:58And one of the things that, you know,
  30. 00:59you start to realize if you look in a
  31. 01:00microscope is that we're covered with
  32. 01:02microbes all over our surface. We're
  33. 01:04covered with microbes all the way in our
  34. 01:06gut. In fact, we can't, you know, you
  35. 01:07can't digest, you've probably heard this
  36. 01:09before, but you can't digest animal fats
  37. 01:11if it weren't for the bugs, the bacteria
  38. 01:12in your gut. They make some of the key
  39. 01:14components of of bile acids that allow
  40. 01:17you to digest animal fats. So, you need
  41. 01:19this system that's around you. So, you
  42. 01:21aren't just the cell like if you learn
  43. 01:23biology, you've got the again, we're
  44. 01:25going to go way back. There's the egg
  45. 01:26and the sperm and they fertilize and now
  46. 01:28you got this this this cell that starts
  47. 01:30to divide and gives rise to every other
  48. 01:32cell in our body. So you might say that
  49. 01:33your body is just that collection of
  50. 01:35cells,
  51. 01:37but in fact it's it's it's it's absorbed
  52. 01:40a lot of viruses and and bacteria from
  53. 01:42our environment. And you know, to go
  54. 01:44into that really briefly, that's really
  55. 01:46important because we only have 20,000
  56. 01:47genes in our genome. So there's only so
  57. 01:50much in a given life that we can do with
  58. 01:51those genes. And so by absorbing all
  59. 01:53kinds of other species onto us, we get
  60. 01:55their genomes. So like you said, like I
  61. 01:57was saying, the the bacteria in your gut
  62. 01:59can now help you absorb nutrients that
  63. 02:01you wouldn't otherwise. If you eat
  64. 02:02sushi, you know, you've heard this
  65. 02:03probably, right? You get you get
  66. 02:04bacteria in your gut that can help you
  67. 02:06absorb the the the seaweed, you know,
  68. 02:09nutrients from seaweed. So, so taking
  69. 02:12this into your question, you know, when
  70. 02:13you're first born, you've never really
  71. 02:15seen anything. And so, two things are
  72. 02:17are I think worth pointing out at the
  73. 02:20early phase of life. One of them is for
  74. 02:22the first six months or so, your immune
  75. 02:23system is pretty poor at being trained
  76. 02:26on things. And it's presumably we
  77. 02:28presume that for those six six months
  78. 02:30that's because your body is developing
  79. 02:31so fast that if you were to have a super
  80. 02:33active immune system you might actually
  81. 02:35find yourself attacking yourself. You
  82. 02:36might think that you're foreign because
  83. 02:38some genes turn on during development
  84. 02:39and then all of a sudden you're you know
  85. 02:41your immune system's like oh I see
  86. 02:43something different and now I need to
  87. 02:44react. So that's well known and that's
  88. 02:46that's one of the reasons why some
  89. 02:47childhood vaccinations they're really
  90. 02:49important to protect kids in long over
  91. 02:51life. Why they aren't given until you're
  92. 02:536 months or or older. But I think to
  93. 02:56your point, one of the things that's
  94. 02:58happening with kids is that they then
  95. 02:59then as they go into their like until
  96. 03:01they're 10 and you're talking about they
  97. 03:02get sick a lot. They just haven't seen a
  98. 03:04lot of these bugs before. So they don't
  99. 03:06have an immune system that knows what
  100. 03:07flu is because they've never seen the
  101. 03:10body's never that body and kids body has
  102. 03:12never seen flu before. So every single
  103. 03:14virus and pathogen that hits it is going
  104. 03:16to elicit some you know some amount of
  105. 03:18illness. But then they have a very
  106. 03:20strong immune system. it reacts and you
  107. 03:22know gets rid of that with the exception
  108. 03:24of the ones that you know are those
  109. 03:25those certain viruses and bacteras mumps
  110. 03:27measles rebella that are they're lethal
  111. 03:29and that's why we immunize as we say and
  112. 03:31that's those are things that your immune
  113. 03:32system if they get too much of those
  114. 03:34kids will die and so it's better to
  115. 03:36protect them with a vaccine all right so
  116. 03:38that's the front end right the front end
  117. 03:40has this initial you know
  118. 03:42imunosuppression then just exposure to
  119. 03:44all these things that are in our
  120. 03:45environment and you and I take on as
  121. 03:48part of our genomes but we have to get a
  122. 03:50we have to reach a taunt with some of
  123. 03:51them. You know, we have to get to the
  124. 03:52point where the immune system can kind
  125. 03:53of like fire back when they show up if
  126. 03:56they're bad and and and allow them to
  127. 03:57live in us if they're good with us. And
  128. 03:59so I think that's what's happening a lot
  129. 04:01in those first years of life. And you
  130. 04:03know, you can see that both in the form
  131. 04:04of, you know, kids getting sick a lot,
  132. 04:05but you'll also see that their guts
  133. 04:07develop way diverse microbiome. You
  134. 04:10know, they allow a whole bunch of things
  135. 04:11that come in from the outside and are
  136. 04:13acceptable and are quite good for you.
  137. 04:16So that's the front end. In the back end
  138. 04:17of life, it's a little bit more
  139. 04:18complicated. But I'll tell you I'll tell
  140. 04:20you two things that I think are

  141. Why Immune Function Declines With Age

  142. 04:21important. On the one hand is the idea
  143. 04:23that is is the fact that a lot of your
  144. 04:25cells in general become less functional
  145. 04:26including immune cells and you get less
  146. 04:29cells produced and and that might just
  147. 04:31be because you know we were never
  148. 04:33selected as organisms to live as long as
  149. 04:35we do right now. That's one idea of
  150. 04:36aging, right?
  151. 04:37We know that that we just were supposed
  152. 04:39to be dead by 70.
  153. 04:40Well, no, but we do know that that we
  154. 04:43can reproduce and and you know pass on
  155. 04:45our genes successfully already when
  156. 04:46we're 16. So you know the selective
  157. 04:49pressure to pass on your genes if you
  158. 04:51imagine that's how genetic evolution
  159. 04:53happens is that you pass on your genes
  160. 04:54as being successful. You can already do
  161. 04:56that at 16 and anything after that is
  162. 04:58just cream on the crop but um you know
  163. 05:01at some point maybe there's no
  164. 05:03selection. So we don't know that but
  165. 05:04it's it's a reasonable hypothesis to say
  166. 05:06there wasn't any real selective pressure
  167. 05:07for passing on genes that do anything
  168. 05:10past when you're actually having kids.
  169. 05:12The psychologists would tell us that uh
  170. 05:14the wisdom of people, you know, 60, 70,
  171. 05:1780 and beyond is useful for um groups of
  172. 05:21humans that live in, you know, you know,
  173. 05:24villages of 100 or so people because
  174. 05:25they can give information to younger
  175. 05:27people that is on the periodicity of
  176. 05:30like every 5 to 10 years, maybe every 30
  177. 05:32years.
  178. 05:34But that's a just so story, right? I
  179. 05:36mean, it's a nice just so story.
  180. 05:37I like it too. And the I think the
  181. 05:39genome geneticists will refer to that as
  182. 05:41like the grandfather effect where genes
  183. 05:43may be selected for and maybe they're
  184. 05:45mostly about you know genes that make us
  185. 05:47social in the in for for for the elderly
  186. 05:50that do you know they're going to have
  187. 05:52effects on the fitness of their
  188. 05:54grandchildren which is their genes.
  189. 05:56And so this yeah I think there's
  190. 05:58something to be said for that in in
  191. 06:00conceptual space. I don't know if I can
  192. 06:02prove it to you that that's
  193. 06:03a tough experiment to do. It's a really
  194. 06:04tough experience to have two villages
  195. 06:06where the you know the grandparents are
  196. 06:07eliminated or like kept you know both
  197. 06:10non-ethical and also non
  198. 06:12but we were talking about the aging

  199. Cellular Mutations & Mosaicism

  200. 06:13immune system and I think I think
  201. 06:14there's two things that again come to
  202. 06:16this question that I was asking you like
  203. 06:17who are you um and I was saying okay
  204. 06:20well in aging you have this issue that
  205. 06:21the immune system is is tapering in its
  206. 06:23efficacy it's many of the cells that you
  207. 06:25you know you've been holding your whole
  208. 06:26life start to to literally they die off
  209. 06:29but there's another thing which is I
  210. 06:31think a lot of people don't realize when
  211. 06:32you say when basic biology ology say
  212. 06:34that sperm, you know, like uh fertilizes
  213. 06:36the egg. So, you've got your mom's genes
  214. 06:37and your dad's genes. You got 23
  215. 06:39chromosomes for your mom, 23 chromosomes
  216. 06:41for your dad. And and and at least in
  217. 06:43when you're first born, every cell is a
  218. 06:45clone. It has exactly the same
  219. 06:47information.
  220. 06:48But DNA replication and and DNA sort of
  221. 06:51like fidelity isn't perfect. Like they
  222. 06:53say that on your skin, the cells of your
  223. 06:55skin may have somewhere between 10 and
  224. 06:5730,000 mutations per cell per day just
  225. 07:00from like basic sun exposure. And it's
  226. 07:02that that's higher than some of the
  227. 07:04other organs. But the basic idea is that
  228. 07:05your DNA, you know, it's susceptible to
  229. 07:07UV radiation. That's one of the reasons
  230. 07:09we put on sunscreen.
  231. 07:11But what it what it practically means,
  232. 07:12no matter what number you put in there,
  233. 07:14whether it's 10,000 mutations per day or
  234. 07:16remember the the genomes are huge,
  235. 07:18right? So 10,000 mutations out of
  236. 07:20terabytes of of of information, still is
  237. 07:23only a certain number. But do that over
  238. 07:24every over years. And the main thing is
  239. 07:27that that means is that every cell in
  240. 07:29your body is no longer identical to the
  241. 07:30one next to it because this one got
  242. 07:32different mutations on day one. This one
  243. 07:34got some mutations on day two. And
  244. 07:36slowly but surely you are becoming like
  245. 07:38a mosaic. And I say mosaic, you know,
  246. 07:40because like the tile that you see in
  247. 07:42Morocco, you know, very intricate
  248. 07:44designs because if you actually, you
  249. 07:46know, start to look into tissue, you
  250. 07:48know, you'll find that certain clones,
  251. 07:49certain mutations do make certain cells
  252. 07:51more fit. And they're the ones that if
  253. 07:53you scratch yourself and a cell has to
  254. 07:55like some some new has to has to form,
  255. 07:57they might be the fittest to fill that
  256. 07:58void.
  257. 07:59And one of the other clones over here
  258. 08:01that got a different mutation may not be
  259. 08:02fit to fill that clone. And so you you
  260. 08:04end up with this pastiche of who you
  261. 08:06are. So now again I ask you like who are
  262. 08:08you now? So if I want to defend against
  263. 08:11something that looks different, what if
  264. 08:14everything looks different? What if
  265. 08:16every cell is different from every other
  266. 08:17cell? It's it's it okay. You want you
  267. 08:21want another analogy? I would like
  268. 08:22another analogy. The only um exception
  269. 08:25that I can think of to this and I could
  270. 08:27be wrong is that our neurons, our
  271. 08:30central nervous system neurons, our
  272. 08:31brain and spinal cord, most all of them
  273. 08:34are the same ones that we were born
  274. 08:35with.
  275. 08:36Same cells, but
  276. 08:37same cells, but so you're saying
  277. 08:38mutations are constantly occurring in
  278. 08:40the neurons in the DNA. So there it is
  279. 08:42fascinating by the way that neurons live
  280. 08:43that long. and you know hair cells that

  281. How Stem Cells & Neurons Are Protected

  282. 08:45they say that the the proteins in in our
  283. 08:47hair hair cells of our ear are the same
  284. 08:49exact molecules atoms as we had when we
  285. 08:53were born. So there's there's some cells
  286. 08:54that are along the but in their nuclei
  287. 08:56the DNA that's encoding who they are who
  288. 08:59those cells are is subject to mutation
  289. 09:01ongoing and it depends on how deep they
  290. 09:03are like the we tend to think that one
  291. 09:04of the reasons that immune stem cells
  292. 09:07live in our bone marrows you know our
  293. 09:08long bones are hollow and in there is
  294. 09:10the source of the immune systems you
  295. 09:13know revitalization it's the stem cells
  296. 09:14that make more white blood cells we like
  297. 09:17to think that they live in there because
  298. 09:18it protects them from a reagent they
  299. 09:21they they they hang out you stem cells
  300. 09:22are You know that the bone actually
  301. 09:24serves not only a structural purpose in
  302. 09:25our body, but they it's a cavity in
  303. 09:27which things can live and
  304. 09:29keep it away from from solar radiation.
  305. 09:31Keep it away from chemical cues in the
  306. 09:33environment that can mutate.
  307. 09:34Sequester your stem cells
  308. 09:36and um
  309. 09:36don't burn them.
  310. 09:38Yeah.
  311. 09:38That kind of thing.
  312. 09:39Yeah. Likewise, the neurons in the in
  313. 09:42the uh inside of the skull.
  314. 09:44Yeah.
  315. 09:44And the spinal cord
  316. 09:45are protected.
  317. 09:46They're protected.
  318. 09:47Yeah.
  319. 09:47And that's interesting. Yeah.
  320. 09:49Yeah.
Why Your Immune System Declines With Age | Dr. Max Krummel & Dr. Andrew Huberman — Transcriptly