Some interesting findings out of Kobe University may have identified genes that control cellular senescence, the process by which a cell deteriorates. Their methods involved a somewhat novel use of liver cancer treatments, and may have implications for both cancer treatments and anti-aging products.
In Brief: Senescence and Apoptosis
Cells continue to divide and grow throughout their lifespan, but there inevitably comes a time when a cell becomes too damaged (from ultraviolet rays, radiation, injury, etc.) to work properly. In these situations, one of two events will occur: growth of the cell will stop (senescence) or it will be deliberately broken down and destroyed (apoptosis). Both of these processes play important roles in the body, one of which is making sure cells don’t uncontrollably grow and become cancers.
A number of cancer treatments are designed to try and trigger the apoptosis process in tumor cells. Unfortunately, cancer cells are notoriously prone to mutation, and treatments can sometimes end up triggering senescence instead of apoptosis. While a non-growing cancer cell is better than a spreading one, it still isn’t ideal. It is also thought that some senescent cancer cells can somehow speed up the malignancy of surrounding cells, so that would be an additional problem.
The researchers made use of liver cancer cells and the anti-cancer drug etoposide. The drug induces apoptosis in high concentrations, but prior research noticed that it triggers senescence in lower amounts. The basic idea was to treat cancerous cells with either no etoposide (A), a low concentration (B), or a high concentration (C), and then use DNA microarrays to see which genes were triggering in each group. The reasoning is that the genes that get expressed more in group B or C would be the ones most important in senescence and apoptosis respectively.
There were 126 genes that were expressed three times as much in the group B cells as in group A, as well as 25 genes that were expressed twice as much in group B as in group C. The over-expression of proteins PRODH, DAO, and EPN3, were also found to promote senescence. More narrowing of the findings ensued, and the result was that six genes in particular, all regulated by p53 (another gene that manages the cell cycle), were found to be involved in the functions of senescence. This involvement took the form of oxidative stress responsive, intracellular balancing systems, and other bodily mechanisms.
What This Means
Finding these genes may lead to treatments that target the senescence process. For instance, combining a senescent-suppressing drug with etoposide could block cancer cells from becoming senescent instead of killing themselves, thus improving treatment effectiveness. Doing so would require a lot more work, but these findings (if confirmed) suggest potential avenues of further research.
The potential application of these findings for anti-aging drugs and lifespan extension is a lot less clear. Cellular senescence does play a role in the aging process, but creating something that turns the process off isn’t going to result in an anti-aging medication. Remember that unchecked cellular growth is what causes tumors in the first place, so recklessly fiddling with senescence in the name of anti-aging is just asking for trouble. Still, the Kobe University findings are interesting and will hopefully open new avenues in cancer research as a result.
Nagano, T., et. al., “Identification of cellular senescence-specific genes by comparative transcriptomics,” Nature Scientific Reports, 2016; 10.1038/srep31758.
“Genes that control cellular senescence identified – Potential applications for cancer treatment and development of anti-aging products,” Kobe University web site, September 13, 2016; http://www.kobe-u.ac.jp/en/NEWS/research/2016_09_13_01.html, last accessed September 14, 2016.