Cancer and aging: Look at firefly mice
Fluorescent mice will help study the aging process and cancer
Nanonews Network based on the materials of the University of North Carolina:
UNC researchers use luminescent mice to track cancer and aging in real-timeScientists have created a strain of mice with the firefly luciferase gene.
This gene is activated when the normal p16 gene, a tumor suppressor and biomarker of aging, is activated. Since the p16 gene is turned on in aging cells, the luciferase gene is also activated, causing the affected tissue to glow.
In an article published in the journal Cell (Burd et al., Monitoring Tumorigenesis and Senescence In Vivo with a p16 INK4a-Luciferase Model), scientists from the UNC Lineberger Comprehensive Cancer Center The University of North Carolina (UNC) describes a new method they have developed for visualizing the aging process and tumor growth in mice using a gene closely related to these processes.
Scientists have long known that the p16 gene plays an important role in the aging process and in suppressing the development of cancer by activating an antitumor defense mechanism called cellular senescence. Distinguished Professor Norman Sharpless, MD, and colleagues have created a strain of mice in which, when the normal p16 gene is activated, the firefly luciferase gene "turns on". In aging cells, the p16 gene is turned on, which activates the luciferase gene and causes the affected tissue to glow.
During the aging process, the expression of the p16 gene progressively increases in the body of mice.
The picture shows young (on the left) and old (in order of increasing age) mice.
Photo: University of North Carolina
Throughout the life of such mice, scientists observed the activation of p16 by simply tracking the brightness of each animal's glow. They found that old mice glow brighter than young ones, and that the sites of cancer formation become especially bright, making early diagnosis of cancer possible.
"Using such mice, we can visualize in real time the activation of the cellular aging process, which prevents the development of cancer, but promotes aging. We can literally see the earliest molecular stages of cancer and aging in the body of living mice," Professor Sharpless comments on the results of his work.
Researchers see the possibility of widespread practical use of these mice today. Visualization of the activation of cellular aging will allow testing of chemicals and other factors contributing to it in the same way as toxicologists detect cancer-causing substances on other strains of mice. Moreover, these mice are already being used by scientists at the University of North Carolina and other scientific institutions to detect the early stages of cancer development and determine the tumor response to various methods of anti-cancer therapy.
Using the new strain, scientists have already made several unexpected discoveries. First, they were able to track the accumulation of aging cells in the body of aging mice, based on the brightness of the animals' glow. Surprisingly, the brightest animals did not show a more pronounced tendency to die from spontaneously developed cancer than dimmer animals of the same age. This means that the number of aging cells is not a predictor of the risk of death from cancer.
"We, and I think others, expected that animals with the largest number of aging cells would develop cancer more often and they would die sooner. But our forecast did not come true," says Dr. Sharpless.
Another surprise was the differences in p16 levels. The researchers studied a large group of genetically identical animals kept in the same conditions and fed the same food. However, despite the identity of genetic and external factors, the brightness of the glow of mice at any age varied significantly, which gives reason to believe that the aging process is influenced by factors outside genetics and nutrition.
Glowing mice can almost literally be called a window into the formation of cancerous tumors, for the suppression of which the expression of the p16 gene is activated at the earliest stages. Usually the activation of p16 prevents cancer, but sometimes this antitumor mechanism does not work, and the tumor still develops, continuing to stimulate the expression of p16. Therefore, all tumors formed in such mice they glow brightly, which allows researchers to observe various types of cancer at the earliest stage of the formation of a neoplasm. Here, scientists also had a surprise: unlike what was expected, p16 was actively expressed not only in the cancer cells themselves, but also in normal neighboring cells.
"These findings suggest that the cause of activation of cellular aging is an abnormal environment surrounding developing cancer. From somewhere, many or all of the cells of the future tumor know that they are in poor conditions, and activate this antitumor defense mechanism, even if they themselves are not cells of the future tumor. This happens at very early stages of cancer development; we are talking about the earliest neoplastic events ever experimentally observed in the body of living animals," Dr. Sharpless emphasizes.
He and his colleagues believe that similar approaches to monitoring cellular aging can be developed for humans, which will allow us to study the aging process and the development of tumors. Working with UNC oncologists, they have already analyzed the expression of p16 in several hundred patients undergoing anti-cancer treatment. These studies, along with the use of luminous mice, aim to develop more effective treatment regimens with the least side effects, which will be based not on chronological, but on the "molecular" age of the patient.
Portal "Eternal youth" http://vechnayamolodost.ru23.01.2013