A recent study suggests that individuals with Laron syndrome, also known as growth hormone receptor deficiency (GHRD), may have a lower risk of cardiovascular disease. GHRD is a rare condition that causes stunted growth due to the body’s inability to properly use its own growth hormone. Research on mice with GHRD has shown a 40% increase in lifespan and reduced risks for age-related diseases.Nevertheless, the potential risk of heart disease in individuals with GHRD has not been clearly understood. This has led to the speculation that this mouse longevity mutation may actually increase the risk of cardiovascular disease in humans. The study, published in Med on April 26, 2024, is the result of nearly 20 years of collaboration between Valter Longo, a professor of gerontology at the USC Leonard Davis School of Gerontology, and endocrinologist Jaime Guevara-Aguirre of the Universidad San Francisco de Quito, Ecuador. Throughout the last two decades, Longo, Guevara-Aguirre, and their colleagues have studied the health of individuals with GHRD.The team’s previous research has shown that the rare gene mutation causing GHRD, found in only 400 to 500 people worldwide, was discovered in a group of Ecuadorians whose ancestors had fled Spain more than three centuries ago during the Inquisition. This mutation causes ineffective growth hormone receptors and leads to a form of dwarfism. Despite the fact that Ecuadorians with GHRD are more likely to be obese, they have a significantly lower risk of cancer and Type 2 diabetes, suggesting that GHRD/Laron syndrome may not only reduce growth but also reduce the risk of several age-related diseases.The study found that individuals with GHRD seem to have healthier brains and perform better on cognition and memory tests. The research team examined the cardiovascular function, damage, and risk factors in GHRD subjects and their relatives. They conducted two phases of measurements in Los Angeles and Ecuador, involving 51 individuals. Of these, 24 were diagnosed with GHRD and 27 were relatives without GHRD who served as controls. Some key findings from the study included: GHRD subjects had lower blood sugar, insulin resistance, and blood pressure compared to the control group, and they also had smaller heart dimensions.The study found that individuals with GHRD had similar pulse wave velocity and stiffness in the arteries but lower carotid artery thickness compared to the control group. Even though they had higher levels of “bad cholesterol,” GHRD subjects had a lower percentage of carotid artery atherosclerotic plaques compared to the control group (7% vs 36%).
According to Longo, the senior author of the study, these results suggest that individuals with GHRD have either normal or improved cardiovascular disease risk factors compared to their relatives. He also noted that while the sample size was small, these findings are supported by studies in mice and other organisms.The human data revealed valuable insights into the health impacts of growth hormone receptor deficiency. It suggests that drugs or dietary changes that produce similar effects could lower disease rates and potentially increase lifespan. Along with co-authors Longo and Guevara-Aguirre, the study also involved Amrendra Mishra and Priya Balasubramanian from USC; Carolina Guevara, Álvaro Villacres, Gabriela Peña, and Daniela Lescano from the Universidad San Francisco de Quito; and Alexandra Guevara from the Instituto de Endocrinologia Metabolismo y Reproducción (IEMYR) in Quito. Additionally, Marco Canepa of the Universi was involved in the study.The study was conducted by Jaime Guevara-Aguirre, Amrendra Mishra, Marco Canepa, Carolina Guevara, Álvaro Villacres, Alexandra Guevara, Gabriela Peña, Daniela Lescano, John J. Kopchick, Priya Balasubramanian, Valter D. Longo. The research was funded by the National Institutes of Health/National Institute on Aging grant P01 AG034906 to Longo.
