June 2, 1998 TORONTO -- A research team led by Dr. Gabrielle Boulianne of The Hospital for Sick Children (HSC) and the University of Toronto (U of T) and Drs. John Phillips and Arthur Hilliker of the University of Guelph has identified a critical weakness in the defence against aging. Using the fruit fly as a model biological system, the researchers discovered that a specific cell type -- the motor neuron -- is the major target for oxidative damage, known for several years to be a key factor affecting aging and lifespan. The researchers were able to boost the flies' defences by inserting a human gene which is known to protect against oxidative damage. As a result, the average lifespan of the flies (usually about 80 days) was increased by 40 percent. Their research is reported in the June issue of the scientific journal Nature Genetics.
"This research is significant because it clears up a long-standing mystery: which cells, when targeted by oxidative damage, limit the lifespan of the entire organism," says Dr. Boulianne, a scientist at HSC and an associate professor of Molecular and Medical Genetics at U of T. "In addition, we now know that just one gene, targeting one type of cell, has a huge impact on aging. Contrary to what was previously thought that many different factors contribute to aging, it now appears that the process may be simpler."
By inserting the human gene SOD1 (superoxide dismutase) into flies, researchers were able to protect the flies against oxidative damage. This damage, which increases with aging, affects a cell's ability to maintain its structure and function.
"One of life's ironies is that the stuff that we need to survive oxygen is actually toxic," explains Dr. Phillips. "When we breathe, toxic byproducts called oxygen radicals are created. Our cells defend against these toxins by either neutralizing or eliminating them. But as we age it becomes more difficult for our cells to cope with the toxins and they accumulate. What we now know is that the nervous system is the most vulnerable to this accumulation because it uses a lot of oxygen."
Oxidative damage has been linked to several human neurodegenerative diseases, including familial Amyotrophic Lateral Sclerosis, Huntington's disease, Parkinson's disease, and Alzheimer's disease.
"Of course, much more research needs to be done in the area of oxidative damage to the motor neurons," explains Dr. Boulianne. "The tools are still being developed that will allow us to selectively target cells in the nervous systems of mice or humans."
In addition to developing the necessary tools, the next steps in this field of research will include identifying other types of cells that are equally important in the aging process. Researchers will also attempt to determine if there are other beneficial actions that can be taken to affect oxygen metabolism.
This research was supported by The Hospital for Sick Children Foundation and grants from the Medical Research Council of Canada and the Natural Sciences and Engineering Research Council of Canada.
Liz Leake, Public Affairs The Hospital for Sick Children 416-813-5046 email@example.com
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