Image of the Week: The experimental diet that mimics a rare genetic mutation
This is an excerpt and image taken from the article, ‘The experimental diet that mimics a rare genetic mutation’ by Peter Bowes, published by Mosaic.
A group of people in Ecuador have a form of dwarfism that protects them against some diseases and ageing. Peter Bowes discovers the science behind their condition, and asks whether the health benefits of this particular genetic mutation could be replicated by a diet involving fasting.
Zvi Laron, a researcher working with people of stunted growth, first identified the condition in the late 1950s.
Laron found that his patients had the body’s primary growth hormone (GH) in abundance in their bloodstream, an observation that seemed to defy logic, since they had stunted growth. He concluded that their dwarfism was caused by damage to GH receptors in the liver. It results in extremely low levels of another growth hormone, known as insulin-like growth factor-1 (IGF-1).
In the normal sequence of events, GH, secreted by the pituitary gland, locks on to GH receptors, initiating the production of IGF-1 in the liver. But if a mutation has caused the receptors to be faulty, there are two major effects: the body is unable to generate IGF-1 and the individual is more sensitive to the hormone insulin, which helps regulate the amount of sugar in the bloodstream.
Because IGF-1 stimulates cells to grow and divide, lack of it is linked to a lower risk of cancer – uncontrolled cell division. Meanwhile, a greater sensitivity to insulin helps to prevent diabetes.
There are about 350 “Larons”, people living with Laron syndrome, today, about a third of whom live in Loja, a remote, mountainous province of southern Ecuador. They grow to about a metre in height and experience delayed puberty.
Historians think that Ecuador’s Larons descended from conversos, Sephardi Jews who converted to Christianity and fled to South America at the time of the Spanish inquisition in the 16th century. At first there may have been just one person who had no outward symptoms but passed on a recessive gene. It is assumed that, over generations, inbreeding in the small, isolated Ecuadorian community led to children being born with copies of this gene inherited from both parents – which causes Laron syndrome.
It was Jaime Guevara-Aguirre who in 1988 began studying Larons living in Ecuador. He has been caring for about 100 Laron patients for the past three decades.
During this time, Guevara-Aguirre has had only one Laron patient die of cancer and none from diabetes. This is in contrast to their relatives without Laron syndrome, who have a death rate from cancer of 17 per cent and 5 per cent from diabetes. Despite higher body fat, Larons have a lower resistance to insulin and a much lower incidence of diabetes. And they do not need to fast to achieve this. They eat what they like and are often obese. Because the mutation in their GH receptors blocks the production of IGF-1 in their bodies, they can get fat and still not develop diabetes.
“They’re the human version of what the research of many groups has shown in simple organisms,” says Valter Longo, biogerontologist and director of the University of Southern California Longevity Institute. Longo and others have shown that you can significantly extend the life of yeast, nematode worms, flies and rhesus monkeys by introducing mutations that affect growth. Scientists have also found that mice, when genetically modified so that their GH receptors are impaired, enjoy lives 40 per cent longer than normal. What’s more, their longer lives are also free of major diseases.
“It’s a remarkable increase in health span, in addition to longevity,” says Longo. He believes the same could apply to humans. The ageing process appears to be controlled, in distantly related organisms, by similar genes and mechanisms. “The thing about the Laron dwarfs in Ecuador,” David Gems, Professor of Biogerontology at the Institute of Healthy Ageing, University College London says, “is that they provide some tantalising evidence that this control of ageing extends from the animal models up to humans.”
This is an excerpt taken from the article, ‘The experimental diet that mimics a rare genetic mutation’ by Peter Bowes, published by Mosaic: the magazine dedicated to exploring the science of life, at the Wellcome Trust. Read the full article on mosaicscience.com.
Image credit: Michael Driver