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Growth hormone holds a conflicted status in the world of life extension. Some believe it turns back the clock, with evidence from humans suggesting that hormone treatment reduces fat and boosts muscle. But animal studies show the opposite: mice without growth hormone live significantly longer and are protected against cancer, one of the most deadly diseases of aging.

Valter Longo, a scientist at the University of Southern California, in Los Angeles, hopes to untangle this conundrum by studying an unusual group of people in Ecuador: those with a genetic mutation that renders them insensitive to growth hormone. “They are the largest population in the world that is growth-hormone deficient,” says Longo. Studies of the group could provide a valuable window into whether growth-hormone depletion could, in fact, be used to extend longevity. The study could also shed light on how to develop drugs against the diseases of aging without introducing unintended side effects.

Growth hormone is a crucial protein produced by the pituitary that directs growth and cell division. People who lack the hormone or the ability to respond to it are extremely short, while those whose hormone levels dip in middle age, such as after damage to the pituitary, have an increased risk of cardiovascular disease. In mice, however, deficiency of the hormone seems to be beneficial. “In the mouse, the effect is major and striking,” says Andrzej Bartke, a biologist at Southern Illinois University in Springfield, who is not involved in the project. “They seem protected from cancer and appear to have delayed aging by various measures. But there is almost no evidence that growth-hormone deficiency would extend life in humans.”

The group Longo plans to study lives in the rural Loja province in the southern portion of Ecuador. These isolated mountain communities have a high rate of an otherwise rare condition known as Laron dwarfism. People with the condition lack a functioning version of the receptor that binds to growth hormone.They are small and obese, but little data exists on their longevity.

Children with the condition seem more susceptible to pneumonia and diarrhea, common scourges of poor rural communities, and they die at twice the rate of their unaffected siblings. Those who survive to adulthood typically have high cholesterol and triglycerides, risk factors for heart disease. Some die of heart disease, an uncommon occurrence in rural Ecuador, but preliminary reports suggest that Laron dwarves are protected from artherosclerosis, arterial hardening that can lead to heart attack. Adding to the puzzle is anecdotal evidence suggesting that they don’t get cancer or type 2 diabetes. “It’s a balance: if you turn down risk of cancer, you might turn up risk of heart disease,” says Steven N. Austad, a biologist at the University of Texas Health Sciences Center, in San Antonio, who is not involved in the project.

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Credit: T. Blundell & N. Campillo, Wellcome Images (top), Valter Longo (bottom)

Tagged: Biomedicine, cancer, longevity, hormone

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