According to a research that was published in Nature, certain genetic mutations that increase the life span in the roundworm Caenorhabditis elegans also decrease the growth of tumors in it. The finding could help us understand why cancer risk increases as we grow older, and may also suggest new targets for cancer therapeutics.
Professor Cynthia Kenyon and colleagues from the University of California, San Francisco, conducted this research. They studied this link in C. elegans, a species that doesn't usually get cancer. "These animals still live twice as long as normal, even though they've got a tumor," says Kenyon. "It's really amazing."
AdvertisementIt may be assumed that genes that promote long life and fight cancer would go hand-in-hand: a gene that protects against tumors would help to stop cancer from killing the person. But actually, the relationship is far more complicated than that. It seems that genes that make some animals live longer, through non-cancer-related mechanisms also have the ability to suppress tumors.
Professor Kenyon made an amazing discovery in 1992, in C. elegans -- a favorite model for developmental biologists and geneticists due to its simple structure and because the entire three-week life is easily scrutinized under the microscope. She found that disabling a single gene, called daf-2, doubled the life of the worm.
The daf-2 gene is now known to be part of a hormonal pathway. daf-2 encodes a receptor for insulin and IGG-1, an insulin-like growth factor. Another gene, daf-16, functions along with daf-2, and its activity is essential to extend life in the mutant daf-2 worms. This affects the aging process by switching other genes on and off. These genes encode proteins that may be responsible for the prevention or repair of damage to other proteins in the cell. These interactions trigger a cascade of cellular responses that include secondary signals that control the longevity of individual tissues in the worm. Life span is influenced by cells in the reproductive system and sensory neurons in the brain.
In the study, the team mutated a tumor suppressor gene called gld-1 in the worms, causing cells in the animals' gonads to divide rapidly and form germ-line tumors. These tumor cells, when left undisturbed, break out of the gonad and fill the body, killing the worm at around 9 days old age.
They then studied the effects of a few different 'longevity' genes in the tumor-affected animals, to assess the influence on lifespan and tumor growth. All of the longevity mutations tested increased the worms' lifespan in spite of them having cancer.
It is a long known fact that insulin boosts growth of tumor in rats. When the insulin levels are reduced in rats by making them diabetic, the tumor growth also slows down. "The study is another example of the intimate tie-in between insulin and tumorigenesis," says David Kritchevsky from the Wistar Institute in Philadelphia, Pennsylvania, who studies the effects of diet on cancer.
"In the worms, lowering insulin levels seems to slow cell division and increase apoptosis - the process by which some cells are able to commit suicide — with a particular impact on tumor cells."
The results indicate that tumor cells are generally more susceptible to the effects of longevity-causing mutations than normal cells. Thus, investigating these long-life mechanisms might provide better ways to fight cancer. Drugs created this way might even have the side effect of extending life further than the normal span for those without cancer.
This study is a significant start in this direction: the short lifespan of the worms makes for a quick study of old age. More human-like models will need to be studied to unravel what is really going on say other experts.
Biologist Siegfried Hekimi of McGill University in Montreal, who studies C. elegans, warns that the laboratory-engineered worm tumors are very different to naturally occurring mammalian ones. "They aren't created by the same mechanism, nor do they spread the same way. So this one study is hard to generalize from. It tells us that these pathways should be studied in vertebrates," he says. "Only then might we be able to explain how ageing relates to cancer," he says.
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