Fight Aging!

The accumulation of senescent cells is one of the causes of aging. If even 1% of the cells in a tissue become senescent, that small fraction has been shown to have very damaging effects on the function and behavior of the majority non-senescent cells. The most direct path towards addressing this problem is to selectively destroy senescent cells throughout the body every few years, and companies such as Oisin Biotechnologies and UNITY Biotechnology are working towards that goal. Many researchers are more interested in altering the behavior of senescent cells for the better, however, something that I see as an inferior path, but that fits more closely with the scientific impulse to completely map senescence as a cellular phenomenon: to produce a full understanding of the molecular biology of the processes involved. Fortunately, the sort of mapping work shown here should also make it easier to selectively target senescent cells for destruction in the years ahead.

Researchers have succeeded in identifying genes that control cellular senescence - permanently arrested cell growth. The process involved treating liver cancer cells using anticancer drugs of various concentrations, inducing apoptotic cell death and cellular senescence, and comparing gene expression levels. By developing drugs that suppress the activity of these genes, this discovery has potential applications for creating new highly-effective anticancer drugs, or use in anti-aging drugs. Living organisms experience various stresses during their lifespans. These stresses include radiation, ultraviolet rays, and chemical substances that directly damage DNA and cause cancer. Organisms are able to speedily repair DNA when it is damaged, but when the damage is severe, they manifest two different cell responses: apoptosis - a type of controlled cell death - and cellular senescence, which permanently suspends cell growth. Both these responses prevent the cell which suffered DNA damage from proliferating and becoming cancerous.

The research group had previously discovered that cell senescence was effectively induced by using low concentrations of anticancer drugs on cancerous cells. If cancerous cells are treated with a low concentration (10 μM) of the anticancer drug etoposide this induces cell senescence, and if they are treated with a high concentration of the drug (100 μM) this induces apoptosis. For this research, they treated cancerous cells under three different conditions: A) with no etoposide; B) with a low dose of etoposide (10 μM); and C) with a high dose of etoposide (100 μM). They then used DNA microarrays to identify the genes in which a rise in transcription levels could be observed. They predicted that genes which showed increased expression in response to treatment B were mainly related to cell senescence, genes expressed in response to C were mainly those involved in apoptosis, and among the genes which specifically showed increased expression in B compared to C would be genes that play an important role in implementing cell senescence.

There were 126 genes where three times as much expression was recorded under treatment B compared to A, and 25 genes that showed twice as much expression in B compared to C. These 25 genes are expected to express specifically in senescent cells since the other factors caused by DNA damage are removed, and researchers confirmed that the genes involved in causing cell senescence were among them. If we can develop a drug that targets and regulates the activity of the genes that control senescence identified in this research, by administering it together with conventional anticancer treatment we can limit the emergence of senescent cells and potentially increase the effectiveness of cancer treatment. Additionally, it has been reported that one of the causes of individual aging is the accumulation of senescent cells. This means that drugs which control cell senescence could have potentially large benefits for the development of anti-aging medication products.

Link: http://www.kobe-u.ac.jp/en/NEWS/research/2016_09_13_01.html