There are three main classes of cells that accumulate in the body during aging to a supernumerary degree: fat cells, senescent cells and certain types of immune cells.

Fat cells tend to grow and/or proliferate to replace the muscle mass that we tend to lose with age. Interestingly, the most conspicuous fat -- under the skin, or subcutaneous -- seems to be relatively harmless in terms of increasing our susceptibility to life-threatening diseases, unless of course it gets to the stage known as "morbidly obese" in which its sheer weight and the strain it puts on the heart are decidedly life-threatening. There is also a tendency, however, to accumulate "visceral" fat -- fat within the abdominal cavity -- and this fat seems to be really bad for us, because it promotes the progressive loss of our ability to respond to nutrients coming in from the stomach. In particular, it causes us to develop insulin resistance -- a diminished ability of insulin to signal our muscle and other cells to absorb and store sugar from the circulation -- and this eventually leads to Type II diabetes. So, we really should try to get rid of the excess visceral fat cells.

The second type of supernumerary cells, senescent cells, accumulate in quite large numbers in one tissue, the cartilage in our joints. They also accumulate elsewhere, but in much smaller numbers; however, these may still be important by being actively toxic. They aren't able to divide when they should, and they also secrete abnormally large amounts of some proteins.

The third type, immune cells, is much more complicated. In brief, the total number of white blood cells in our bodies seems not to change very much with age, but some subsets of them become more numerous and others less. Of particular interest are "memory cytotoxic T cells", because people infected with certain viruses, especially cytomegalovirus (which most of us have, in fact), accumulate a huge number of this type of immune cell that is specifically reactive against proteins encoded by that virus. Interestingly, it seems that most of these cells aren't actually working very well anyway -- they have become dysfunctional, a bit like senescent cells mentioned above (and possibly for the same reason, stopping themselves from dividing uncontrollably as cancers). Hence, it is important to bring these cells down in number in order to leave room in the "immunological space" for others to expand as needed; we probably don't need to worry that this would allow the virus to harm us (though it would certainly be good to get rid of the virus too if we can, and work is intensive on this, because people with a compromised immune system, such as AIDS sufferers, often experience serious symptoms from these viruses). Certain other types of immune cell seem also to become dysfunctional during aging, and again this may be because they've divided often enough that DNA damage responses are kicking in to stop them dividing much more. You might think that the sensible thing for a cell to do in such circumstances is just to die, but that might cause other, similar cells to divide more and incur more DNA damage, so there may be an advantage to the organism to have the cell hang around taking up space even if it can't do its proper job.

Getting rid of cells is a much simpler job than most of the other things we have to do as part of SENS. In the case of fat, it's possible to use simple surgery, but that's unnecessarily invasive. There are two main other ways: we can inject something that makes the unwanted cells commit suicide but doesn't touch other cells, or we can stimulate the immune system to kill the target cells. Both approaches involve making use of distinctive molecules on the surface of the target cells: luckily, different cell types tend to have different things on their surface, so this shouldn't be too hard. But it hasn't been done yet, and not enough people are working on it -- it needs much more attention. The immune case may in fact not need to be addressed directly, because it may be done automatically as a simple side-effect of my preferred anti-cancer therapy, WILT. WILT involves, among many other things, the genetic manipulation of blood stem cells, the cells that give rise to T cells. Thus, T cells can be made more controllable in terms of their willingness to die on demand, by additional genetic manipulations done to the stem cells.

Talks on this topic at IABG 10:
Barzilai      Campisi