Could a rare mutation that causes dwarfism also slow ageing? (Nature)

#1

More news on the potential benefits of low IGF-1:

People with Laron syndrome have a deficiency in the growth hormone receptor that prevents their bodies from properly using the hormone. These individuals have normal or high levels of growth hormone but low levels of insulin-like growth factor-1 (IGF-1), which normally helps growth hormone to promote the growth of bones and tissues.

Because having low IGF-1 levels has been associated with a higher risk of cardiovascular disease5, “everybody assumed that people with Laron probably had a lot of heart and cardiovascular problems, too”, says Longo. A previous study by the same group found that people with Laron syndrome had a normal rate of death from cardiovascular disease1. But when Guevara-Aguirre investigated some of the deaths attributed to heart attacks, he found inconsistencies. “People in those little towns sometimes attribute any death without an explanation to myocardial infarction because it’s the easiest thing,” he says.

The researchers performed a series of tests that showed that people with Laron syndrome actually had normal or improved levels of cardiovascular-disease risk compared with their relatives without the disorder.

Drug inspiration?

Haim Werner, a geneticist at Tel Aviv University in Israel who studies the protective effects of Laron syndrome against cancer, says that the current work is important in helping to characterize genes and pathways that might confer protection against cardiovascular disease. “Delineation of these genes is of crucial importance for future nutritional or pharmacological interventions,” he says.

Longo hopes that the recent results might inspire the development of new strategies to prevent cardiovascular disease in people without the condition, perhaps an oral drug to bring IGF-1 levels down by targeting the growth hormone receptor. “We just have to find out how to do it safely, so that we don’t make things worse,” he says.

Full article: Could a rare mutation that causes dwarfism also slow ageing?

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#2

I believe Nir Barzilai has written about this and made a connection to centenarians who he believes also has this genetic predisposition to inability to take up IGF-1 into the cells. He also sees this as a possible example of antagonistic pleiotrophy: short stature, reduced fecundity (early menopause?), combined with longer life.

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#3

Some more good stories on this latest research and the Laron Syndrome dwarfs:

“We have shown in studies people with Laron have a very low incidence of cancer, diabetes and cognitive decline,” said Longo, who has studied Laron syndrome for nearly 20 years. “Brain scans have shown they have more youthful brains — the equivalent of someone 20 years younger. I have yet to see a case of Alzheimer’s in this population.”

Longo highlights that diets that mimic fasting, which he himself has designed, lower IGF-1 levels in the circulation, the supposed cause of the beneficial effects observed both in animals and in people with Laron. Another of the authors of the work, John Kopchick, from the University of Ohio, has shown that several molecules that block the growth hormone receptor slow tumor progression in mice and in human breast cancer cells, and improve the effectiveness of conventional treatments. One of these molecules is Pegvisomant, an already approved drug manufactured by the multinational Pfizer to treat acromegaly, a hormonal imbalance that causes excessive growth of the face and extremities.

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