A study illuminates potential cardiovascular health benefits in individuals affected by a rare condition known as growth hormone receptor deficiency (GHRD) or Laron syndrome.
GHRD is characterised by the body’s impaired ability to utilise its growth hormone, resulting in stunted growth. In mice, this condition has been linked to an unprecedented 40% extension of lifespan and reduced susceptibility to various age-related illnesses. However, the association between GHRD and cardiovascular disease risk in humans has been uncertain until now, leading to speculation that this longevity mutation observed in mice might elevate cardiovascular risk in humans.
Published in Med on April 26, 2024, the study is the culmination of nearly two decades of international 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.
Over the past twenty years, Longo, Guevara-Aguirre, and their team have investigated the health and ageing processes among individuals with the genetic mutation responsible for GHRD. This rare mutation, identified primarily among Ecuadorians whose ancestors fled Spain during the Inquisition over three centuries ago, results in ineffective growth hormone receptors and a form of dwarfism.
Previous research by the team indicated that while GHRD (Laron syndrome) diminishes growth, it also appears to reduce the risk of several age-related diseases. Despite a higher incidence of obesity among Ecuadorians with GHRD, they demonstrate lower rates of cancer and Type 2 diabetes. Moreover, they exhibit healthier brain function and superior performance on cognitive and memory tests.
For their latest study, researchers assessed cardiovascular function, damage, and risk factors in GHRD subjects and their unaffected relatives. The study involved two phases of data collection conducted in Los Angeles and Ecuador, encompassing 51 participants, including 24 diagnosed with GHRD and 27 control subjects without the condition.
There are some key findings from the study. GHRD subjects exhibited lower blood sugar levels, reduced insulin resistance, and lower blood pressure compared to their unaffected relatives. They displayed smaller heart dimensions and comparable pulse wave velocity (a measure of arterial stiffness) but had thinner carotid arteries compared to the control group.
Despite higher levels of low-density lipoprotein (LDL) cholesterol, GHRD subjects showed a trend towards fewer atherosclerotic plaques in their carotid arteries compared to controls (7% vs 36%).
“These findings suggest that individuals with GHRD may have either normal or improved levels of cardiovascular disease risk factors compared to their unaffected relatives,” commented Longo, senior author of the study. “While the study sample size is limited, when combined with findings from research involving mice and other organisms, these human data provide valuable insights into the health implications of growth hormone receptor deficiency. They also suggest that pharmaceutical treatments or dietary interventions capable of replicating these effects could potentially reduce disease incidence and extend lifespan.”
The study underscores the complex interplay between growth hormone receptor deficiency, metabolic health, and cardiovascular risk, offering new avenues for further research and potential therapeutic strategies to enhance longevity and mitigate age-related diseases.
More information: Jaime Guevara-Aguirre et al, Normal or improved cardiovascular risk factors in IGF-I-deficient adults with growth hormone receptor deficiency, Med. DOI: 10.1016/j.medj.2024.03.022
Journal information: Med Provided by University of Southern California
