If the accumulation of senescent cells are so detrimental to the tissues in which they reside, why haven’t we evolved mechanisms to remove them? The answer is that we probably have, but the mechanism which removes them from the tissues becomes impaired as with age.
To understand how this removal system may work, we need to look at the phenotype of senescent cells. Although a large number of the changes which occur during cellular senescence may be cell specific, there appears to be features which are common to the majority of senescent cell types. These include the secretion of growth factors, matrix degrading proteins (MMPs) and the production of cytokines. Since these factors are a common feature, it is likely that they have a common function and are not just a random consequence of the changes which occur during senescence.
One possibility is that senescent cells are removed by the immune system. Senescent cells secrete cytokines to attract immune cells to their location (for their removal), secrete matrix degrading proteins to allow the immune cells easy access and secrete growth factors to stimulate the proliferation of surrounding cells for its replacement once the cell is removed. However, since the immune system itself is governed by ageing mechanisms, its ability to remove senescent cells gradually decreases, therefore the accumulation of senescent cells gradually increases.
The majority of the work on the immune clearance of unwanted cells has been carried out in cancer research. The prevalence of cancer as we all know increases with age, and this may be due to an ageing immune system, consequently resulting in an impaired ability to remove cancer cells as they appear. Over the past several years it has become clear that the immune system plays a crucial role in preventing cancer. As a consequence, there has been a great deal of interest in using our bodies own immune system to recognise and destroy cancer cells (FDA, cancer research uk), a process which could potentially be used to target and destroy senescent cells in ageing tissues.
Publication
DGA Burton (2008) Cellular senescence, ageing and disease. AGE
2 comments:
I totally agree. I think that was the coolest part from the Scott Lowe liver paper last year.
Here's a curious thought though: general inflammation is increased with age which includes a number of the macrophagic markers they looked at in their paper, so presumably the innate immune system is being signaled at an even higher level in old than young, but maybe it is not responding (except for rhumatoid arthritis??).
Someone please rejuvinate the immune system in an old mouse and look at the effects on the levels of resident senescent cells!!
A cancer related question - Does research indicate that perhaps the body is producing cancer fairly often throughout all stages of life? If so, does a robust immune system then take care of eliminating the cancer and that is a reason why cancer early is life is relatively rare?
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