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Jaime Guevara-Aguirre with patients who have Laron syndrome  (Source: online.wsj.com)
A 22-year study of those with Laron syndrome in the Andes mountains leads researchers to believe that a deficiency in growth hormone activity can help prevent cancer and diabetes

Valter Longo, a cell biologist from the University of Southern California, and Jaime Guevara-Aguirre, an endocrinologist from Ecuador, conducted a 22-year study that revealed that those with Laron disease are less susceptible to cancer and diabetes

The 22-year study consisted of Longo and Guevara-Aguirre following a remote community in the Andes Mountains. Several of the members of this community have Laron syndrome, which is a deficiency in a gene that stops the body from utilizing growth hormone. Researchers followed 100 people with Laron syndrome along with 1,600 relatives of "normal stature."

Longo and Guevara-Aguirre found that those with Laron disease did not develop diabetes over the 22-year period, and only one non-lethal case of cancer was diagnosed. As far as the 1,600 relatives go, 5 percent developed diabetes in the same time period while 17 percent were diagnosed with cancer. 

"The growth hormone receptor-deficient people don't get two of the major diseases of aging," said Longo. "They also have a very low incidence of stroke, but the number of deaths from stroke is too small to determine whether it's significant." 

Since both groups were exposed to the same genetic and environmental risk factors, the researchers have a reason to believe that growth hormone activity in adults who are beyond their growing years can be harmful. 

While those with Laron syndrome seem to dodge two of humanity's most common diseases, the lifespan for both groups were about the same. According to the researchers, the family members with Laron syndrome tend to die from substance abuse and accidents more than anything else. 

"Although all the growth hormone deficient subjects we met appear to be relatively happy and normal and are known to have normal cognitive function, there are a lot of strange causes of death, including many that are alcohol-related," said Longo. 

At this time, it is not fully understood how growth hormone deficiency protects people from certain diseases, but Longo found that serum from a subject with Laron syndrome protects DNA from oxidative mutations and damage, yet also causes the suicide of severely damaged cells. Those with Laron syndrome have very low insulin levels as well as low insulin resistance, which could explain why they do not become diabetic.  

Researchers plan to use the information from this 22-year study to create drugs that are capable of reducing growth hormone activity, but there are many precautions and risks that need to be assessed before developing such treatment. For instance, the treatment would need to show milder effects than drugs used against a "confirmed disease." Also, it would have to be used for preventative reduction of growth hormone in adults with high hormone activity in order to bring it to a normal level, and not to the low levels of those with Laron syndrome, which could produce even more problems for the individual. In addition, the treatment would be used only on those with a history of diabetes or cancer at first.

Presently, there are already FDA-approved growth hormone-blocking drugs strictly used for the treatment of acromegaly, which is closely related to gigantism. Also, mice studies conducted by John Kopchick have shown that the life of a mouse can be extended by 40 percent when the growth hormone is blocked. Kopchick also found that growth factor deficiency led to reduced tumor risk in mice. 

According to Longo, drug treatments are not the only way to reduce growth hormone activity. Natural methods like restricting calories and proteins in the diet seem to have a similar effect. But the study also added that restricting specific nutrients could have adverse effects as well, causing more harm than good. 

Longo and Guevara-Aguirre now plan to seek approval for a clinical trial to test preventative growth hormone-reducing drugs on patients undergoing chemotherapy, since mouse models and human cells have been protected against chemical damage in previous studies. They hope this can lead to effective drugs that can prevent cancer and diabetes, and help others live similarly to the way those with Laron syndrome do in the Andes Mountains - disease free.  

"It's the dream of every administration, anywhere in the world," said Longo. "You live a long healthy life, and then you drop dead."

This study was published in Science Translational Medicine.





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