Washington, Dec 2 : For the first time, researchers have found how cellular senescence, the well-known mechanism for preventing cancer, can trigger aging and age-related disease by changing the local tissue environment.
In cellular senescence, cells shut down and stop dividing when their DNA is damaged, thus preventing damaged DNA from leading to unregulated cell division and therefore cancer.
But in the new study, researchers have found that when these cells shut down they also spew proteins into their surrounding environment. This causes inflammation and sets up conditions that support the development of age-related diseases including, cancer.
"We provide for the first time a broad molecular description of how this well known mechanism for cancer prevention drives aging and age-related disease by changing the local tissue environment," said Judith Campisi, PhD, lead author of the study, who is a Faculty Member of the Buck Institute for Age Research.
It was found that the senescent cells secrete inflammatory, growth-stimulating, immunomodulatory, and other proteins that dramatically change the tissue microenvironment, both in cells grown in the lab and in people undergoing chemotherapy, which can cause DNA damage.
Also, the researchers showed that normal cells that acquire a highly active, mutant version of a cancer-promoting protein known as Ras secrete higher levels of the tissue-altering molecules, as do cells that lose functions of the tumour suppressor protein p53.
Thus, the study explained why the presence of senescent cells can promote the growth and aggressiveness of nearby precancerous or cancer cells.
It also defined a new mechanism by which precancerous or cancer cells that have lost the p53 tumour suppressor, or gained an oncogene such as Ras, promote cancer so efficiently.
"This study defines a new paradigm for how oncogenes promote, and how tumor suppressor genes suppress the development of cancer. The established role for these genes is to control the cell itself. Our findings show that both types of genes also strongly change the tissue microenvironment, and therefore control cancer by mechanisms that depend not only on the response of the affected cells themselves, but also on the response of neighboring cells, or the local tissue environment," said Campisi.
Campisi said the findings also help explain why cancer patients feel so sick when they get chemotherapy.
"Chemotherapy is brutal -- both normal and cancerous cells are forced into senescence, with resulting secretion of inflammatory factors that can produce flu-like symptoms during treatment," she said.
On one hand she emphasized that chemotherapy can cure cancer, while on tyeh other she said the study provides a cautionary note for younger patients who receive treatments that could promote the development of further cancers later in life.
Campisi said the study points out the need for new biologically targeted therapies for cancer that exploit more specific differences between normal and cancer cells.
Now, the researchers are planning to continue their research involving efforts to encourage the body to eliminate senescent cells more rapidly than it normally does.
The study was published in the latest issue of PLoS Biology.