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Old 02-18-2011, 05:39 PM   #1
Exclamation Clue to diabetes, cancer seen in short Ecuadoreans

WASHINGTON (AP) - In remote villages of Ecuador, scientists have found a population that may hold clues to fighting diabetes and cancer - people with a type of dwarfism who almost never get those diseases.

It turns out that a gene mutation that stunts their growth also may block cell changes that lead to these diseases of aging.

Researchers tracked the health of 99 Ecuadoreans with what's called Laron syndrome. Most stand shorter than 4 feet because the gene mutation prevents their bodies from properly using growth hormone.

That alters the activity of other hormones, including insulin-like growth factor or IGF-1 - a substance that laboratory studies suggest might be manipulated to lengthen lifespan.

So scientists were interested in seeing how people with Laron syndrome fare.

Over 22 years, this population experienced no diabetes and only one non-lethal case of cancer, Ecuadorean endocrinologist Jaime Guevara-Aguirre and University of Southern California cell biologist Valter Longo reported. Their research appears in Wednesday's issue of the journal Science Translational Medicine.

The absence of diabetes was true even though the Laron population tends to be heavier than other Ecuadoreans, and being overweight raises the risk for diabetes.

In contrast, 1,600 of the group's normal-height relatives who lived in the same towns experienced rates of those diseases typical of Ecuador - 5 percent got diabetes and 17 percent got cancer.

However, the Laron patients didn't live longer than their taller relatives. Their main causes of death were accidents and alcohol-related illnesses, Longo said.

For their research, scientists mixed components from the Laron participants' blood with human cells. Longo's team found those components protected against types of cellular damage and altered some genes that laboratory studies have linked to life extension.

Next, Longo wants to test if there are safe ways to use medications that block growth hormone activity in ways that might protect against diseases of aging. But that research will take years.
Old 02-18-2011, 05:42 PM   #2
Group of Short Ecuadoreans Holds Anti-Aging Secret 8 mins ago

A group of short-statured Ecuadoreans has surprised scientists, not for its members' dwarfism, but because they are also immune to cancer and diabetes. Now scientists think they've figured out the group's healthy secret.

The individuals have Laron syndrome, a rare disease that causes stunted growth in about 250 people worldwide. Scientists have known the syndrome results from a mutation in a gene that regulates how cells grow and divide. And it turns out the mutation's effect on a growth-signaling pathway in the body also leads to resistance to cancer and diabetes.

Laron syndrome

Laron syndrome results from a mutation in the gene that codes for growth hormone receptor (GHR), a protein that binds with the human growth hormone and ultimately results in the production of the insulin-like growth factor 1 (IGF1), causing cells to grow and divide. When a person has two of these mutated and non-working genes, they can develop the disease.

High levels of IGF1 have been implicated in cancer and diabetes in previous studies, and low levels have been found to cause increased longevity in everything from yeast and worms to mice.

"In worms, we don't see diabetes or cancer or anything once we establish this potential [to extend life] in worms, we moved to mice," said Felipe Sierra, director of the Division of Aging Biology at the National Institute on Aging. "We do see similar things in this study [of humans], and it validates everything we do."

Sure enough, in the short-statured Ecuadorean group, the study revealed that deficient growth hormone receptor led to low levels of IGF1, and this was associated with the disease-resistance.

"If, in fact, these deficiencies in the growth hormone receptor are extendable to everyone else, then you could, with a drug that was already available, reduce the incidence of cancer and diabetes," said lead study author Valter Longo of the University of Southern California.

(Some humans, such as the late actor Andre the Giant, develop the opposite disease acromegaly, which is also known as giantism. Those with acromegaly have excess human growth hormones that cause them to grow continually, typically reaching heights over 7 feet. Those who develop acromegaly are also known to have a higher risk for cancer, diabetes and premature death. They are often given a drug called Pegvisomant, which blocks the growth hormone's actions.)

Short stature, healthier life

In the Laron syndrome study, the team took several steps to form a complete picture of how this mutated receptor causes the short stature syndrome (and lack of disease) in humans, since researchers had already observed life-span extension in other studies.

"A bunch of people had done extensive work in mice that are growth hormone deficient, or growth hormone receptor deficient they have life span extension about 40 percent," said Longo.

Jamie Guevara-Aguirre, a doctor in Ecuador who is experienced in treating Laron patients, led the analysis of the Laron-syndrome group and their relatives via a questionnaire about their health. Guevara-Aguirre then followed a group of 100 of these individuals, ages 10 and up, for 22 years. He also tested their IGF1 levels.

The Laron-syndrome group had lower levels of IGF1, none of them were diabetic, and only one had cancer, which was non-fatal. Their relatives, not affected by Laron, had normal levels of death from cancer and diabetes 5 percent and 17 percent, respectively.

Though none of the Laron group died of these diseases, they didn't live any longer than their unaffected relatives instead, the study found they had higher rates of death from various accidents and alcohol-related issues. "They died of a lot of strange causes of death," Longo said. "It looks like they, in general, die of acute conditions, and some of them may be because of their behavior, in particular the behaviors of males."

Step by step

Interestingly, the study participants had elevated levels of obesity, but didn't get diabetes, rates of which have increased in the general population along with the obesity epidemic.

"What's interesting is the same thing is observed in the mice; they are protected against insulin resistance and diabetes, and they are slightly obese," Longo said. The reaction of mice and people to the same genetic change is remarkably similar, he added.

The researchers are also testing relatives of the group who have only one copy of the mutated growth hormone receptor gene to see if they show any of the positive effects that are seen in those with two copies.

Longo is planning to run clinical trials with IGF1-lowering drugs on cancer patients undergoing chemotherapy. By decreasing IGF1 levels in these patients to normal levels, they will be able to see if they are protected from further effects of the disease.

But Sierra cautions that these insulin-growth pathways are complex, and changing them may lead to other complications. High levels of IGF1 have been linked to diabetes and cancer in previous studies of humans, but nailing down the precise mechanism has been difficult.

"Everything is inter-related in our bodies. In general, I panic when people jump to conclusions too fast," Sierra told LiveScience. "We are not at a point where we can do actual experiments in humans."

The study will be published Thursday (Feb. 17) in the journal Science Translational Medicine.

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