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    • Imagine living in a 4-foot body that doesn't develop chronic diseases

    Laron syndrome is a recessive gene, so only those who receive a copy from each parent will be affected. (Professor Longo via CNN Newsource) Laron syndrome is a recessive gene, so only those who receive a copy from each parent will be affected. (Professor Longo via CNN Newsource)
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    In the Los Angeles restaurant where Nathaly Paola Castro Torres works, customers never fail to comment on her short stature.

    鈥淧eople stare at me too much and make comments or jokes,鈥 Torres, 42, said. 鈥淢any times they also (take) photos of me and I don鈥檛 like it. I feel very bad.鈥

    At four-foot-two (127 centimetres), Torres is a 鈥渓ittle person鈥 who isn鈥檛 used to such reactions. While she was growing up in Quito, Ecuador, people seldom mentioned her height. She worked at a car dealership, felt embraced by her community, and considered her size an advantage.

    鈥淪ince I was a teenager, I saw my height as (an opportunity) to develop 鈥 the growth problem is part of my personality,鈥 Torres told CNN in Spanish.

    鈥淚 am also quite lucky because in reality my body protects me a lot from diseases that other people have every day,鈥 she added. 鈥淭his height, at the same time as being a limitation, is also a blessing.鈥

    Torres has a rare disorder called Laron syndrome that is caused by a genetic mutation. It stunts her growth but also provides a hidden silver lining: Her body is protected from chronic diseases such as cancer that often take life away long before old age.

    鈥淚 wonder what people who make fun of Nathaly would say if they knew she lived in a body that may some day provide information on how to live longer, disease-free lives,鈥 said Valter Longo, professor of gerontology and biological sciences at the University of Southern California in Los Angeles.

    鈥淲e have shown in studies people with Laron have a very low incidence of cancer, diabetes and cognitive decline,鈥 said Longo, who has studied Laron syndrome for nearly 20 years. 鈥淏rain scans have shown they have more youthful brains 鈥 the equivalent of someone 20 years younger. I have yet to see a case of Alzheimer鈥檚 in this population.鈥

    And according to a new study in the journal Med, Torres and other people who have the condition may also be protected from heart disease, Longo said.

    鈥淚t doesn鈥檛 mean that they are immune to these diseases, but people with Laron syndrome certainly seem to be very protected,鈥 added Longo, who was a coauthor of the latest research. 鈥淭his is how powerful this mutation seems to be.鈥

    Professors Valter Longo (tallest in back) and Dr. Jaime Guevara-Aguirre (left of Longo) pose with participants of their study on Laron syndrome. (Professor Longo via CNN Newsource)

    What is Laron syndrome?

    The first cases of little people who seemed to shrug off disease were among children of Jewish immigrants from Yemen and other parts of the Middle East. Today, there may be between 350 and 500 people with Laron syndrome in the United States, Ecuador, Israel, Croatia, Ireland and other European countries, Longo said.

    In 1987, Dr. Jaime Guevara-Aguirre, then a young physician just starting his career, discovered a group of about 100 people with Laron syndrome scattered across rural towns in Ecuador. Guevara-Aguirre, who was first author of the new report, is the founder of the Institute of Endocrinology, Metabolism, and Reproduction in Quito.

    These people all carried a mutation in their human growth hormone receptor gene, according to Guevara-Aguirre鈥檚 research. That genetic disruption blocks the body鈥檚 ability to use insulin-like growth factor, or IGF-1, a hormone created primarily in the liver. Growth hormone and IGF-1 work together to promote normal bone and tissue growth, so a deficit stunts growth.

    People with Laron have IGF-1 in their tissues, where it can be called upon to help heal wounds and other body processes. However, unlike the rest of us, these folks have little of the hormone circulating in their bloodstream, where it wreaks havoc and contributes to aging.

    Fortunately, the lack of circulating IGF-1 also blocks the uncontrolled growth of cancer cells and creates an extra sensitivity to insulin that protects against diabetes.

    In 2005, Guevara-Aguirre reached out to Longo, who had been studying a similar mutation in yeast cells that extended their existence.

    鈥淚n addition to yeast cells, worms, flies and mice with similar mutations all live extraordinarily long lives,鈥 Longo said. 鈥淢ice with the same mutation we are studying in humans hold the record in longevity 鈥 they live 40 per cent longer than mice without it, and 50 per cent of those mice never develop any pathology. So they are living longer and healthier lives.鈥

    The two began to collaborate, hoping they might identify a drug that could potentially be used to lower circulating IGF-1 in the general population and provide antiaging and disease-preventive benefits, Longo said.

    鈥淭he idea would be for people who have high circulating IGF-1 levels to get drugs that lower the IGF-1 back to the range that seems to be associated with the lowest mortality rate, much like people take a drug for high cholesterol,鈥 Longo said.

    A western diet packed with protein and sugar also increases circulating levels of IGF-1, thus hastening aging, Longo said.

    鈥淭here are IGF-1 lowering diets, such as fasting for five days a month, which is called a fasting-mimicking diet,鈥 he said. 鈥淲e have which found circulating IGF-1 levels remained depressed for a while after doing this.鈥

    Guevara-Aguirre and Longo are also looking for funding to provide IGF-1-boosting injections to children in Ecuador born with Laron syndrome. Given during childhood to encourage height, the drugs could then be stopped to allow the mutation鈥檚 genetic protection against disease to take over.

    鈥淪o far, the (Ecuadorian) government and pharmaceutical companies will not pay for it,鈥 Longo said. 鈥淲e are having to do it more slowly with diet, and we have had a bit of success.鈥

    New study on heart disease

    There are health risks connected to Laron syndrome as well. The condition leads to extreme obesity, a trigger for diabetes, heart disease, cancer and other diseases. In addition, many of the people Longo studies 鈥渘ever exercise鈥 and often drink, smoke and reside in disadvantaged communities without adequate health care, he said.

    Instead of dying from chronic diseases connected to obesity, however, there is an unusually high rate of alcohol- and accident-related deaths as well as convulsive disorders among the Laron population, he said.

    And because low levels of IGF-1 in those without the mutation have been linked with a higher risk of cardiovascular disease, 鈥渆verybody assumed that people with Laron probably had a lot of heart and cardiovascular problems, too, especially considering their obesity,鈥 he added.

    To find out, Longo and Guevara-Aguirre examined Torres and 23 others with Laron syndrome and compared them with 27 of their first-degree relatives without the condition, most of whom live in Ecuador.

    鈥淲e found people with Laron certainly do not have an increased incidence of cardiovascular disease despite the fact that they are often obese and live in poor environments, and some markers of cardiovascular disease were even improved,鈥 Longo said.

    People with Laron in the study had better insulin sensitivity, lower blood pressure and no heart rhythm disturbances 鈥 all positive outcomes, he said.

    In addition, people with Laron syndrome had plaque deposits in their arteries of only seven per cent despite having high cholesterol, which typically leads to clogging of the arteries and a higher risk of heart attacks, stroke and other heart diseases.

    The control group of first-degree relatives, who shared the same diet and lifestyle, had plaque deposits of 30 per cent, Longo said.

    However, additional signs of cardiovascular wear and tear were absent from the study, leaving some questions unanswered, said Dr. Andrew Freeman, director of cardiovascular prevention and wellness at National Jewish Health in Denver.

    鈥淪till, I think it鈥檚 an interesting and promising study,鈥 said Freeman, who was not involved in the research. 鈥淚t lays the groundwork to see what we learn from this to reduce harms that affect people as they age.鈥

    Hope for the future

    Torres recently went to the doctor for a checkup. While technically overweight at 100 pounds (45.4 kilograms), she was in good health, with no signs of diabetes or heart disease.

    鈥(The doctor) tells me, 鈥業f you want, you can lose weight, but it鈥檚 not a health problem for you, you鈥檙e perfect,鈥欌 Torres said. 鈥淚 feel very fortunate and find the response of my body to these other more serious diseases very interesting.鈥

    She plans to stay in the United States to take advantage of educational opportunities and to see whether she 鈥渃an get a chance for a better job, a career.鈥 However, she said she misses her family and the ease of purchasing fresh fruits and vegetables abundant in Ecuador.

    鈥淚 learned is that even though my body is a little more adaptable, I still have to be careful with my diet,鈥 she said. 鈥淏ecause although it is true that we have a health advantage over other people, we do not know for sure to what extent this will protect us.鈥

    She also said she鈥檚 proud of her role in the research on Laron syndrome.

    鈥淭he objective is to be able to develop some medical help in order to help the rest of the people who struggle with diabetes and cancer, two of the most catastrophic diseases,鈥 she said. 鈥淭his is my hope.鈥

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