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Changes in innate and adaptive immunity during human ageing 2

Part 2 of 2
Published on October 16, 2022   23 min

Other Talks in the Series: The Immune System - Key Concepts and Questions

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0:04
Finally, we'll just talk a little bit about the third bit of the puzzle here. This is that low-grade chronic systemic inflammation - inflammageing - that we talk about.
0:16
Again, to the context of the hallmarks, three of the key ones I think are involved are altered intracellular communication, cellular senescence and loss of proteostasis.
0:27
One of the original findings that we had in the lab a number of years ago now is, again, using the VZV challenge model. I appreciate this graph looks horribly complicated, but it's actually really simple. There are only certain things we need to look at. On the very left-hand side, you will find young donors which have VZV, and on the right, you see older donor VZV challenge. If you just look at the normal and the VZV columns, you see, more or less, between old and young that they kinda look the same. The responses are more or less the same in both. It was interesting because we're very good scientists, we are very diligent, we decided to have a control for injecting something into the arm and, of course, we used saline because that's what the VZV antigen is in. When we did this in young people we see there's no response. Saline, the body isn't supposed to respond to this. But when we looked in older people, we started seeing, you can see it here, the red rectangles in this graph. The immune system was responding to a saline challenge in older people. This indicates that perhaps the immune system is just more aggravated in older people's tissues. On the right-hand side, I'm showing you this horribly detailed complicated table, it's just a long list of different genes that we saw being activated in response to saline. But a key bit to note here is all the asterisks on this graph. They all denote genes that are in part at least regulated by this molecule p38. p38 is a very ubiquitous driver of many processes, one of which is inflammation. We thought this was really interesting that in all the tissues when you just give them saline, we all of a sudden start seeing evidence that p38 is doing quite a lot.
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Changes in innate and adaptive immunity during human ageing 2

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