Dr. Jaime Guevara has been studying the Laron Dwarfs for 25 years, for the last decade he has been collaborating with Dr. Valter Longo, a well-known researcher on aging at the University of Southern California. This week the two men released the findings of the research in the Science Translational Medicine Journal.
Laron Dwarfs carry mutations in the growth hormone receptor (GHR) gene that lead to severe GHR and IGF-1 (insulin-like growth factor–1) deficiencies. These mutations offer them protection from cancer and diabetes. A 22 year study of the Larons has confirmed that none has ever had diabetes and only one had cancer and that cancer was not lethal. In contrast, the study looked at 1,600 normal-height relatives who live in the same towns and found that despite similar lifestyles 5 percent got diabetes and 17 percent got cancer.
A possible explanation for the very low incidence of cancer was suggested by in vitro studies: Serum from subjects with GHR deficiency reduced DNA breaks but increased apoptosis in human mammary epithelial cells treated with hydrogen peroxide. Serum from GHR-deficient subjects also caused reduced expression of RAS, PKA (protein kinase A), and TOR (target of rapamycin) and up-regulation of SOD2 (superoxide dismutase 2) in treated cells, changes that promote cellular protection and life-span extension in model organisms.
Unfortunately, Laron patients don’t live longer than their taller relatives. Many have emotional problems related to their Dwarfism and so the main causes of death are substance abuse and accidents. I wish there was a set of biomarkers of aging that would provide some insights into the causes of death of these patients, other than the above. This could help rule out all of the biological consequences of growth hormone receptor deficit and give us some clues about what can be done to prolong life and get rid of not only cancer and diabetes, but of all the other diseases of aging.