May 28, 2008
Aubrey de Grey: Senescent Immune Cells Take Up Valuable Space

A couple of days ago I argued immune system rejuvenation is one of the top rejuvenations I'd like to get. Well, in some recent comments Aubrey de Grey describes how part of immune system rejuvenation could be done by killing off senescent CD8 T cells.

Another area of SENS that is completely separate from cancer is the elimination of cells that won’t die. Of course cancer is a problem of having too many cells because the cells are dividing like crazy. They are also dying like crazy, but they are dividing even more crazily. That’s what cancer is. There are other problems that are caused by cells that are actually not dividing, but they are not dying either, and they are accumulating slowly as a result. They get in the way and cause various problems just by being there.

Probably the most serious example of this is the immune system. In the immune system we have a wide range of different types of white blood cells that have different functions in protecting us from infections. They have a large number of different things to do. There is one particular type of white blood cell called a cytotoxic T lymphocyteCD8 is the name of the protein that these cells express on the surface—that is the main problem in respect to this accumulation of cells that I mentioned.

Here is what happens: Some viruses that we get are what are called “persistent,” which means that we get this infection and the immune system brings it under control, there are no symptoms, but the immune system does not succeed in completely eliminating the virus from the body. The virus hangs out, latently, in one or two places. There is a particular family of viruses called the herpes viruses, which are particularly bad at this. Within the family of herpes viruses, there is one virus called cytomegalovirus, which used to be considered completely harmless and uninteresting from a medical point of view.

Cytomegalovirus, clinically, does not present any obvious symptoms except in people who have got advanced AIDS or other really severe problems with their immune system. It seems to be the number one reason why you have these CD8 cells accumulating in old age in most people. Most people are infected with CMV from an early age. The way it seems to work is that these CD8 cells, which are specific to CMV and are involved in controlling it, divide. They essentially get rid of a lot of the virus but not all of it, and every time that the virus tries to have another go, it gets beaten back, but it gets beaten back by another round of division of the same family of cells.

What seems to happen is a sort of somewhat variant form of what is called replicative senescence in virto—the concept that so many of you heard about from Len Hayflick fifty years ago, whereby cells end up, due to telomere shortening, getting into a state where they cannot divide anymore. Now, in the immune system, there is a lot of cell division that goes on, and for that reason, telomerase is turned on when it is needed. But, probably as a secondary anti-cancer strategy, cells in the immune system—especially CD8 cells—do not like to do that indefinitely. They get into a state where the sort of stimulus that would normally make them proliferate and turn on telomerase, only makes them proliferate and not to turn on telomerase very much. It leads to an interesting state where they will not divide at all. It will neither divide nor turn on telomerase.

The ability to kill cancer cells attracts a lot more attention. But the ability to kill senescent cells is badly needed as well. If we could kill off old CD8 cells that would make more room for immune cells that can still attack and kill pathogens. But even better, a younger immune system would do a better job of killing cancer cells. So kill older copies of one kind of cell in order to allow a younger copies to kill cancer cells. We need this capability just as we need the capability to kill cancer cells directly.

Share |      Randall Parker, 2008 May 28 10:24 PM  Aging Mechanisms

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