Werner syndrome is a rare premature aging disorder that affects 1 in 200,000 in the U.S. Those afflicted by the syndrome are short in stature; suffer hair loss/graying of hair, cataracts and often conditions that are typically found in those who are much older, including type 2 diabetes, diminished fertility, arteriosclerosis, osteoporosis, and some types of cancer. Life expectancies are usually limited to late 40s or early 50s. New research out of Canada has found hope for this unusual condition through the use of vitamin C treatments.

When Michel Lebel, PhD, currently an associate professor at Laval University’s Centre de Recherche en Cancerologie at the Hopital Hotel-Dieu de Quebec, was completing his post-doctoral work in the laboratory of Dr. Philip Leder at the Harvard Medical School (1996-2000), a group of scientists discovered the gene responsible (when mutated) for Werner syndrome. “I rapidly became interested in this gene and generated a mouse model by mutating the same gene in mice,” he said, noting that the genetic mutation in mice had an effect similar to what they observed in humans with a higher frequency than the normal aging population. “That is,” he said, “these mice developed diabetes, exhibited abnormally high levels of triglycerides, cholesterol, high blood sugar, insulin resistance (type 2 diabetes to be more precise), obesity, accumulation of fat in liver and abdomen (fat belly), heart failure and different types of cancers.”

After opening his own laboratory in 2000 at the Quebec City Cancer Research Center of Laval University, Dr. Lebel and his colleagues continued their studies. “My big question was how come a mutation in one gene can lead to so many diseases related to aging. Werner syndrome is considered the disorder closest to what you see in the normal aging population,” he recalled. “And, of course, what can we do to reverse or slow down these age-related processes?”

Dr. Lebel said he found several interesting characteristics associated with his Werner syndrome mouse model, but the one aspect that really aroused his interest was the increased oxidative stress that was measurable in the tissues of these mice before many of the metabolic abnormalities presented. “My laboratory thus started to treat these mice (including control normal mice) with different antioxidants like the ones found in green tea, red wine and of course vitamin C,” he said. “Up to now I can tell you that vitamin C had the best impact and a positive one on mutant mice. These mice are healthy with vitamin C and live up to the normal life expectancy for normal mice.

“The other interesting result was that normal mice did not extend their life expectancy,” he continued. “Vitamin C had a beneficial impact on mutant mice (we call them Werner mutant mice in my laboratory), which suggests that mice predisposed to develop age-related diseases will benefit from vitamin C supplementation. Other studies on mice and rats that are predisposed to diabetes or Alzheimer’s have also shown beneficial effects of vitamin C. Experiments on other mouse or rat models (with predisposition to certain or several age-related diseases) are encouraging. Treatment of Werner syndrome patients with vitamin C is also encouraging.”

The full results of more than a decade of this research were recently published in The Journal of the Federation of American Societies for Experimental Biology (FASEB Journal, Vol. 24 January 2010).

More Research Warranted

Presently, Dr. Lebel and his colleagues are seeking money to take their research to the next phase, which will involve examining the sequence of the Werner gene (WRN gene) in human subjects that have histories of age-related diseases and compare them to healthy aged subject (of the same age). “There are evidences in the scientific literature that certain changes in the WRN gene sequence in some individuals (called polymorphisms) put them at a higher risk for certain or several age-related disorders,” said Dr. Lebel. “My colleagues and I have recruited subjects in different parts of the world to examine the sequence of the WRN gene (situated on chromosome 8) and see whether there is a significant association between the WRN sequences and age-related diseases in the normal population.”

If the research team observes good associations between specific WRN polymorphisms (polymorphism is what makes every individual different from one another and unique, except for identical twins) and age-related diseases, then it will be possible to test whether supplementation with vitamin C can reduce the risks of developing age-related diseases in humans. “Age-related diseases are complex processes and different genes may affect the course of such diseases,” commented Dr. Lebel. “The WRN gene is one of them. These studies will indicate whether everyone that is at high risk of age-related diseases can benefit from a vitamin C supplement or only those individuals with a specific WRN gene sequence. This is important because there are a lot of controversies about the benefits of vitamin C supplementation.”

When asked to extrapolate the age-related benefits of vitamin C to the average consumer, Dr. Lebel said that a daily dose of vitamin C has its place alongside a balanced diet and exercise. “By eating a balanced diet, the body will automatically absorb the necessary amount of vitamin C required for good health and to reduce the risk of developing these diseases prematurely,” he said. “As for people with a family history of some age-related diseases, we need still need to test whether a specific dose of vitamin C will be beneficial for them in appropriate human trials. These age-related diseases are complex processes involving many genes. The WRN gene is one of them. In case subjects where the WRN sequence is abnormal, the prediction is that vitamin C would be beneficial.”

For those individuals suffering from the rare Werner syndrome, it appears that Dr. Lebel’s research offers a ray of hope. Based on the mouse study, animals (or subjects) with a mutation in the WRN gene will benefit from vitamin C supplementation. Moreover, vitamin C will reverse the abnormal metabolic traits, enabling patients to have a healthy life and normal life span. (It is important to note that the researchers stressed vitamin C will not extend a normal life expectancy.)

“Although additional experiments are required (and encouraged), our results suggest that subjects that are predisposed or are at higher risk of developing age-related disease may benefit from vitamin C supplementation,” he said. “At the present moment, there are contradictory results regarding the beneficial impact of vitamin C and several age-related diseases. We need to determine which genes are responsible for the progression of the diseases and determine which subjects (with specific mutated genes) will benefit from vitamin C supplementation. Again some ill patients may respond to vitamin C treatment and some may not depending on the doses administered. This is what we need to determine.”