Do Zombie cells promote arterial disease?

It’s a fact of life that we’re all ageing, all the time. And as we age, an increasing proportion of the cells in our tissues become “zombified”: they aren’t dead, but they’re no longer properly alive either, and they’re definitely trouble makers. Speaking with Katie Haylor, Cambridge University’s Martin Bennett studies how these so-called "senescent cells" might be linked to heart disease...

Martin - Cell senescence describes a point in a cell’s life where it can no longer divide. It’s basically reached old age in cell terms but it hasn’t quite yet died. The importance of that is that the cell can’t fulfil its function, and is also at that stage generates inflammation. There’s a lot of excitement about cell senescence at the moment. A whole range of diseases. So senescent cells have been identified in heart disease, in dementia, in liver disease, in kidney disease, in arthritis. And increasingly we’ve been able to work out the consequences of having senescent cells. What that means is there may be potential treatments based upon eliminating these cells in the future.

Katie - Can you explain how this relates to a concept of a whole person ageing?

Martin - As we age, a greater proportion of our cells become senescent. There are certain tissues in the body which constantly regenerate, so your bone marrow for instance regenerates forming blood, but many other tissues can’t regenerate if they get damaged, particularly the brain and heart. What that means is that as the cells age, they are not replaced and you have more and more of these sort of almost like zombie or undead cells around the body. They’re not killed, they’re not cleared, but they can cause damage.

Katie - So they’re kind of dormant?

Martin - No. They’re not dormant because they’re very, very active. They can’t fulfil their function, so if they’re a liver cell they can’t perform a normal function to the liver cell or a kidney cell, likewise, or a heart cell or a blood vessel cell. But what they do do is lots of detrimental other things. They signal to other cells causing inflammation.

We’re particularly interested in cells that make up the blood vessel lining, because when those become senescent, again, they can cause problems with the blood vessel function. But we study patients who have heart attacks or have strokes and those diseases are caused by what’s called “atherosclerosis.” Increasingly, we can find senescence cells in those atherosclerotic plaques. They cause a problem because they promote inflammation and they stop the normal blood vessel cells functioning properly.

What’s exciting is some fairly new data that’s come out that suggests that if you clear those cells, then you can improve the functioning of  many many organs in the body, and you may even be able to prolong lifespan. So we talk about lifespan and healthspan. Healthspan is the number of years that you have of healthy living. Lifespan is, obviously, until you die. And removal of senescent cells may actually promote and improve function of many organs as well as potentially improving lifespan as well.

Katie - Wow, okay. So there is the potential to extend the life of organs? Even ourselves, or is that in the realm of science fiction?

Martin - No. It’s not in the realms of science fiction. Certainly, in animal models, removal of these senescent cells has been shown to improve function of many many organs. To slow, or in some cases, partially reverse particular diseases and, in some creatures, can actually extend their lifespan as well.

Katie - Is there any possibility of instead of removing these senescent cells, these cells that are no longer dividing, of reactivating them in some way?

Martin - Yes. Another option is instead of removing them is just switching them off. So if you don’t get rid of them but you just stop them producing things that cause inflammation; that may be just as good. Switching them back on again is more challenging because they have irreversibly reached this state, and if you try and kick them back into making them divide, then the danger is you might generate cancer. So we would prefer to either get rid of them or just switch off the proinflammatory side of things.

Katie - What would you envision for the next 5/10 years in terms of finding these senescent cells and getting rid of them?

Martin - We’re getting much much better at finding them. And we’re getting very much better at working out how they signal, how they’re controlled, and what their consequences are. There’s also major interest now from industry, to design drugs to remove these cells silently. Because you can imagine, if they’re present throughout the body, and if you can remove them, then you may improve functioning of many many organs associated just with ageing.