With advancing age ever more cells in any given tissue in the body are found to be in a senescent state. These cells have permanently exited the cell cycle in response to damage or stress, most likely in order to suppress cancer risk, but their accumulation causes progressive harm to tissue structure. One promising approach to removing this contribution to degenerative aging is the use of targeted cell destruction therapies, such as those under development in the cancer research community. Periodic clearance of senescent cells would prevent the dysfunction they cause, and while this research is poorly funded in comparison to its potential, a few groups are working on it.
Cellular senescence is a process in which cells at risk of becoming cancerous adopt a state of permanent growth arrest. While this process prevents tumor formation (a cell that does not divide cannot become a tumor), senescent cells may also cause or contribute to aging and age-related conditions. The senescent phenotype is complex, and consists of many changes to the nature of the cell: permanent arrest of cell division; morphological changes; beta galactosidase expression and other epigenetic changes including the senescence-associated secretory phenotype in which senescent cells secrete a myriad of factors with potent biological activities. This senescence-associated secretory phenotype, or SASP, is the most potentially damaging effect of senescent cells. While senescent cells account for less than 10% of total cells in aged tissues, the SASP allows these cells to play a much larger role than their relatively small numbers would otherwise suggest. It is hypothesized that this aspect of senescent cells is what drives aging or age-related conditions.
Senescence as a therapeutic target for aging. If senescent cells are so bad, why not get rid of the genes that cause the formation of senescent cells in the first place? Evidence from humans and animals indicates this is not an effective strategy. For example, mutations in the retinoblastoma or P53 genes, the two most essential pathways for senescence, result in strong predisposition to cancer. Therefore, the loss of the cells' ability to undergo senescence would cause a person to die of cancer long before they would grow old enough to worry about the effects of senescent cells.
What about killing the senescent cells that have already formed in the body? This could allow cells to senesce and prevent cancer, but could then eliminate them from the body before they produce harmful effects. In 2011, a group of researchers decided to test this idea using a mouse engineered to kill senescent cells when the mice were given a drug. The results were astonishing: the mice were prevented from developing a host of issues including cataracts and loss of fat, hair, and muscle. They proved to be healthier in most ways than untreated mice. This new therapeutic option, termed "senolysis" (lysis or breaking down of senescent cells), is currently being tested by several aging researchers for its effectiveness in treating the conditions of old age.
Now that senescent cells have been demonstrated to cause many of the conditions of old age, the field of senescence research is primed for a renaissance that could result in a host of new strategies for the therapeutic treatment of aging.