Research has appeared today in PLoS Biology revealing that when human cells enter a state of senescence resulting from genetic damage, they release factors into their immediate environment that cause inflammation and promote cancer.

When cells experience genetic damage, for example as a result of radiation or oxidative stress, if that damage is severe enough, they enter a state of senescence. They no longer divide because to do so would risk abnormal growth and malignancy due to their heavily corrupted genome.

However, while this response exists supposedly to suppress cancer, these senescent cells develop a condition known as SASP – senescence-associated secretory phenotype, which means they secrete factors into the cellular microenvironment that might contribute to age-related pathologies by promoting inflammation and malignancy.

The exact composition of these secretions is not yet known, remaining to be elucidated in further study.

This is thought to be an example of ‘antagonistic pleiotropy‘ – an evolutionary theory suggesting that if one gene controls multiple outcomes, some of which are good in early life and favor reproduction but are bad in later life, they will nevertheless be selected for. In primordial natural environments, hazards abound and old individuals are rare, so their is little pressure from the environment for organisms to evolve such that old individuals are favored. Similarly in humans, given that our reproductivity ends in mid life, there is no evolutionary advantage gained from living to a ripe old age.

As we age, the number of senescent cells increases, and high concentrations of these cells are often found at the sites of age-related pathologies such as osteoarthritis and atherosclerosis, both of which are thought to be caused, or at least facilitated, by chronic inflammation.

In fact, the tumor suppressor gene p53, if chronically active, promotes cellular senescence and therefore also accelerates aging.

Hence, the more cancer-resistant you are, the sooner you are likely to experience the effects of age.

Ultimately, what this might mean for anti-aging is that future study should focus on methods to remove senescent cells from the body, or at least reduce the likelihood of cells becoming senescent in the first place. It’s not clear from the study whether cells that have become senescent as a result of telomere shortening also exhibit SASP, but if so this might explain the seemingly sudden acceleration of the aging process in later life.

Also, it would be excellent if terminally damaged cells committed apoptosis rather than senesced, and hopefully further research will look into how the apoptotic pathway could be favored. Also, methods to differentiate and selectively kill senescent cells or block the expression of SASP would be highly appreciated!

Reference: Jean-Philippe Coppé et al. Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor. PLoS Biology. 2 December 2008