One component of aging is the damage caused by senescent cells, those that have stopped dividing, have not destroyed themselves in a form of programmed cell death or otherwise been removed from the picture, and have started to do a variety of things that are harmful to surrounding cells over time. Removal of senescent cells, say by adapting one of the many flexible and precise cell killing technologies being developed in the cancer research community, is one of the line items in the Strategies for Engineered Negligible Senescence:

So-called 'senescent' cells are those that have lost the ability to reproduce themselves. They appear to accumulate in quite large numbers in just one tissue (the cartilage in our joints), but even in these small numbers they appear to pose a disproportionate threat to the surrounding, healthy tissues, because of their abnormal metabolic state. Senescent cells secrete abnormally large amounts of some proteins that are harmful to their neighbours, stimulating excessive growth and degrading normal tissue architecture. These changes appear to promote the progression of cancer.

Why do senescent cells accumulate with age? And accumulate they do:

the Brown team began to study aging animals - baboons living on a research preserve that ranged in age from 5 to 30. In human years, that age range is roughly 15 to 90. ... For replicative senescence, the most important biomarker is telomere dysfunction-induced foci, or TIFs. Presence of these structures signals that the protective chromosome caps called telomeres have dwindled enough to halt cell division. ... What they found: The number of senescent cells increased exponentially with age. TIF-positive cells made up about 4 percent of the connective tissue cell population in 5-year-olds. In 30-year-olds, that number rose as high as 20 percent.

Over at Ageing Research, some thoughts on the matter:

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.

...

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.

Which is plausible, and those unremoved senescent cells sit there releasing biochemicals that damage and misdirect cells in the surrounding tissue. The aging immune system has a lot to answer for already, in terms of the damage done due to its decline, and it wouldn't surprise me to see more items added to the list.

Posted by Reason at June 2, 2008 3:24 PM | TrackBack (0)