Link Between Cancer-Causing Gene and Aging

A gene called Myc (pronounced “mick”), which is one of the most important triggers of cancer in both mice and humans, also plays a newly discovered crucial role in the aging process, according to research conducted by UPMC Children’s Hospital of Pittsburgh and the University of Pittsburgh School of Medicine. The research, led by Edward V. Prochownik, M.D., Ph.D., Paul C. Gaffney Professor of Pediatrics in the Division of Hematology/Oncology at UPMC Children’s and professor in the Department of Microbiology and Molecular Genetics, has implications for newer forms of cancer therapy.

After Myc Was Eliminated, Rapid Aging Began

Myc has long been difficult to study because mouse embryos die before birth when this gene is removed. This suggests that the gene plays a fundamental role in normal growth and development. According to Prochownik, it was therefore virtually impossible to understand the role of Myc beyond the embryonic stage. To overcome this major hurdle, Prochownik and his team waited until the mice were about a month old before inactivating the gene. “Given the importance of Myc for normal tissue and cancerous tissue, it was crucial for us to know whether these mice would die just like the embryos,” said Prochownik. “We waited nervously for a few days after knocking out the gene in the first group of mice and were relieved when we found that they survived. This allowed us to study the mice for much longer, which is what we had always wanted to do.”

Within a few weeks of eliminating Myc, the researchers noticed that the mice began to age rapidly: their fur turned gray, they lost some of their fur, and they were weaker, less coordinated, and less active than normal mice of the same age. They also developed many metabolic disorders commonly associated with aging. Despite aging more quickly, however, the mice lived up to 20% longer. At first, the researchers could not explain the puzzling phenomenon of the rapidly aging mice living longer. The answer only became clear at the end of the study when they summarized the autopsy results of the mice that had died naturally. The cancer rate in the Myc knockout mice was more than three times lower than in normal mice.

Development of Drugs That Inhibit Myc to Slow Tumor Growth

Prochownik suspects that mice lacking the Myc gene, which is so important for the development of cancer, were unable to develop tumors. This theory is supported by the finding that most of the few tumors that did occur in the knockout mice expressed Myc again, suggesting that tumors tended to arise from a small population of cells that were able to evade Myc inactivation from the outset. The team also analyzed several thousand tissue samples from young and old humans and mice. In both species, normal aging was associated with a gradual decline in Myc expression, but this was not sufficient to prevent the occurrence of various types of cancer.

Some people live to be 100 and remain quite healthy and active, while others age quickly and die at 65. What distinguishes these people? Other studies have shown that Myc is expressed to varying degrees in different individuals, and researchers suspect that people with naturally lower Myc levels age faster than people with high levels. Malfunctioning Myc has been linked to the development of numerous types of cancer in children and adults, prompting many pharmaceutical companies and researchers, including Prochownik himself, to work on developing drugs that inhibit Myc to slow or reverse tumor growth.