Laron syndrome is a form of dwarfism that occurs in a small human population all descended from a single mutant ancestor. It is of interest to aging researchers because the mutation is on the growth hormone receptor, analogous to that approach used to engineer the present record holder for mouse longevity, the growth hormone receptor knockout (GHRKO) lineage. These dwarf mice live 60-70% longer than their peers. However, as is the case for the differences in the long-term outcome of calorie restriction between mice and humans, there is no sign that Laron syndrome produces any meaningful lengthening of life. Human longevity has evolved to be much less plastic than that of short-lived mammals in response to circumstances and changes - such as those involving growth hormone - that affect insulin metabolism, and Laron syndrome is one of the illustrations of that point.
In the remote villages of Ecuador, 100 very small people may hold the key to a huge medical breakthrough. They all suffer from Laron Syndrome, an incredibly rare genetic disorder that stops them from growing taller than 4 feet but also seems to protect them against cancer and diabetes and maybe even heart disease and Alzheimer's. "There's only one patient that has died of cancer among all of the subjects. And that is fascinating," said Dr. Jaime Guevara-Aguirre, who has been studying the Laron population for 30 years.
The project has two goals: figuring out how to distill the anti-disease properties of Laron Syndrome into a medication that could be used to fight cancer, diabetes and other illnesses in the rest of the world, and getting treatment that could help young people with the syndrome grow to full size. "The complaint of these little people was, 'We're doing so much for you. What are science and the pharmaceutical companies, etc., doing for us?'" said Dr. Valter Longo, a longevity specialist.
Laron Syndrome was first identified in 1950 and there are only 350 people with it in the world, all descended from a single ancestor who introduced the mutated gene thousands of years ago. A third of them live in isolated communities in Ecuador, while others live in Spain. Unlike others with dwarfism, Laron patients don't lack growth hormone, but they have a defect in the receptor in the liver that is supposed to bind to the hormone and produce a substance called insulin-like growth factor 1. In Laron, there is no binding and no IGF-1 - and stunted growth as a result. But the absence of IGF-1 may also prevent the uncontrolled growth of cells that turn into cancer, and it creates extra sensitivity to insulin that serves as a shield against diabetes.
Longo duplicated Laron in lab rats. "The mice actually lived 50 percent longer and get a lot less diseases. It's very clear in the mice. Can it be true for people?'" His lab is testing drugs that would block IGF-1 in people, but the question is whether medicine will work as well as an actual mutation in humans. Longo said it will be at least a decade before they know the answer. Meanwhile, his team is also investigating its theory that Laron may be a defense against heart disease and Alzheimer's. Preliminary results show that at the very least, the little people don't have any higher risk of those conditions. The researchers say Laron patients tend to live just as long as their average-sized siblings.