To try to determine how the hormone impacts diseases of aging, Longo plans to compare rates of cancer, heart disease, and diabetes, as well as longevity data, in those with one or two copies of the gene and their unaffected relatives. Those who carry one functioning copy of the growth-hormone receptor appear normal; if they are protected against cancer and do not suffer from obesity and heart disease, they may represent a happy medium of growth-hormone exposure. So far, the scientist has genotyped about 300 people–100 with two copies of the mutation, and 200 relatives and controls.
“If blocking growth hormone is associated with an improvement or decreased incidence of cancer, there are tools that we have as physicians to address that,” says Pinchas Cohen, a pediatric endocrinologist at the University of California, Los Angeles, who has treated children with Laron dwarfism. Drugs that inhibit secretion of the hormone or block its action already exist. And drug companies are now testing blockers of a molecule that acts downstream of growth hormone, called IGF-1, as a treatment for cancer. If IGF-1 works, it’s not yet clear if the most effective intervention will be as a preventative measure, perhaps targeting families with a history of cancer, or if growth-hormone or IGF-1 depletion could be used as a cancer treatment.
Not everyone is optimistic that limiting growth hormone in people will have the same effects it does in mice. “Growth hormone in humans is different than that of most mammals,” says Austad. It has a broader mechanism of action and appears to have evolved rapidly since we diverged from other mammalian ancestors. “No one knows why,” says Austad, “but something has happened to make growth hormone very different in humans.”