Navigation Links
UNC researchers use luminescent mice to track cancer and aging in real-time
Date:1/17/2013

Chapel Hill, NC In a study published in the January 18 issue of Cell, researchers from the University of North Carolina Lineberger Comprehensive Cancer Center have developed a new method to visualize aging and tumor growth in mice using a gene closely linked to these processes.

Researchers have long known that the gene, p16INK4a (p16), plays a role in aging and cancer suppression by activating an important tumor defense mechanism called 'cellular senescence'. The UNC team led by Norman Sharpless, MD, Wellcome Distinguished Professor of Cancer Research and Deputy Cancer Center Director, has developed a strain of mice that turns on a gene from fireflies when the normal p16 gene is activated. In cells undergoing senescence, the p16 gene is switched on, activating the firefly gene and causing the affected tissue to glow.

Throughout the entire lifespan of these mice, the researchers followed p16 activation by simply tracking the brightness of each animal. They found that old mice are brighter than young mice, and that sites of cancer formation become extremely bright, allowing for the early identification of developing cancers.

"With these mice, we can visualize in real-time the activation of cellular senescence, which prevents cancer but causes aging. We can literally see the earliest molecular stages of cancer and aging in living mice." said Sharpless.

The researchers envision immediate practical uses for these mice. By providing a visual indication of the activation cellular senescence, the mice will allow researchers to test substances and exposures that promote cellular aging ("gerontogen testing") in the same way that other mouse models currently allow toxicologists to identify cancer-causing substances ("carcinogen testing"). Moreover, these mice are already being used by scientists at UNC and other institutions to identify early cancer development and the response of tumors to anti-cancer treatments.

"This work builds on previous work by the same group, as well as others, showing intriguing relationships among aging, cancer and cell senescence. It provides a valuable new tool to probe these relationships," said Felipe Sierra, Ph.D., director of the Division of Aging Biology, National Institute on Aging, NIH.

The researchers used these mice to make several unexpected discoveries. First, the group was able to track the accumulation of senescent cells in aging mice by assessing how brightly each mouse glowed. Surprisingly, the brightest animals were no more likely to die from spontaneous cancer than dimmer animals of the same age. That is, the number of senescent cells in the mouse did not predict its risk of dying.

"The result we, and I think others, predicted is that the animals with the highest number of senescent cells would get more cancers and die sooner, but this was not the case" said Sharpless.

Another surprise came from the disparities in p16 levels among the mice. The authors studied a large group of genetically identical animals that were all housed in the same way and fed the same diet. However, despite identical genetic and environmental conditions, the brightness of individual mice at any given age was highly variable, suggesting that factors beyond genetics and diet influence aging.

The glowing mice also provide a window into the formation of cancers. Expression of p16 is activated in the earliest stages of cancer formation to suppress cancer. Usually activation of p16 prevents cancer, but rarely this tumor suppressor mechanism fails and tumors develop, while still activating the p16 gene. As such, all tumors forming in these mice strongly glowed, allowing researchers to monitor early tumor formation in a wide variety of cancer types. In contrast to expectations, the researchers also found that p16 was activated not only in the tumor cells themselves, but also in normal, neighboring cells.

"This finding suggests that activation of senescence results from an abnormal milieu within a developing cancer. Somehow, many or all the cells in a would-be tumor know they are in a bad place, and activate this tumor suppressor gene as a defense mechanism, even if they are not the would-be cancer cells themselves. This occurs really early in the cancer; we're talking about the earliest events of neoplasia that have ever been measured in living animals," said Sharpless.

The Sharpless group believes similar approaches to monitoring senescence can be developed in order to study aging and tumor development in humans. The group is particularly interested in how cancer therapies influence human aging and patient outcome. Working with UNC oncologists, the Sharpless group has already measured p16 expression in several hundred patients undergoing cancer therapy. These studies, along with efforts employing the glowing mouse, aims to develop more effective and tolerable patient treatment schemes based upon 'molecular', as opposed to 'chronologic', age.


'/>"/>

Contact: William Davis
william_davis@med.unc.edu
919-966-5906
University of North Carolina Health Care
Source:Eurekalert  

Related medicine news :

1. NIH awards $20 million over 5 years to train next generation of global health researchers
2. Researchers develop a new cell and animal model of inflammatory breast cancer
3. Researchers uncover a viable way for colorectal cancer patients to overcome drug resistance
4. Researchers Find Gene Mutations That May Be a Key to Autism
5. Researchers find evidence of banned antibiotics in poultry products
6. NJ stroke researchers report advances in spatial neglect research at AAN Conference
7. Autism by the numbers: Yale researchers examine impact of new diagnostic criteria
8. Researchers Map Brain Regions Linked to Intelligence
9. Researchers ID Genes That May Determine Mental Illness
10. Researchers Develop Blood Test for Depression
11. University of Cincinnati researchers win $3.7M grant from US Department of Defense
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
UNC researchers use luminescent mice to track cancer and aging in real-time
(Date:9/22/2017)... ... September 22, 2017 , ... Global ... diseases through research, education and awareness, today announced the appointment of Timothy J. ... microbiologist, Dr. Sellati has more than 20 years of research experience with Lyme ...
(Date:9/21/2017)... ... September 21, 2017 , ... SABRE is raising awareness about personal ... to the end of November. , The Chicago, Illinois, based self-defense brand has been ... them about the ease of taking their personal safety into their own hands. , ...
(Date:9/21/2017)... Virginia (PRWEB) , ... September 21, 2017 , ... ... health in their communities, nine governmental public health departments have been awarded five-year ... accreditation decisions mean that the benefits of being served by a PHAB-accredited ...
(Date:9/21/2017)... ... September 21, 2017 , ... The New England Center for Children® ... the election of Yie-Hsin Hung to the Board of Directors. , “The New ... Directors. Ms. Hung is an invaluable addition to our team,” said Vincent Strully, Jr., ...
(Date:9/21/2017)... ... ... FlipBelt, the fitness brand that specializes in problem solving fitness accessories, has ... the launch of their FlipBelt Crops. , The new fitness bottoms feature an integrated ... at the gym, on the trail, or on-the-go. , “We always thought the FlipBelt ...
Breaking Medicine News(10 mins):
(Date:9/9/2017)... Sept. 8, 2017 Dealmed Medical Supplies, ... of medical equipment, supplies, drugs, vaccines, and specialty medical ... into an agreement to acquire Vantage Medical Supplies, a ... Holtsville, New York . ... new and emerging medical practices, will operate under the ...
(Date:9/7/2017)... Sept. 7, 2017  Eli Lilly and Company ... to streamline operations to more efficiently focus resources ... cost structure. Global workforce reductions, including those from ... to impact approximately 3,500 positions. ... annualized savings of approximately $500 million that will ...
(Date:9/7/2017)... , Sept. 7, 2017 Caris ... focused on fulfilling the promise of precision medicine, ... validate the benefits of its molecular profiling approach ... utilized comprehensive genomic profiling plus (CGP+) with Caris ... patient,s tumor on a molecular level, leading to ...
Breaking Medicine Technology: