Study finds potential cardiovascular benefits in rare longevity mutation

Individuals with growth hormone receptor deficiency may also possess a surprising advantage when it comes to cardiovascular health.

A recent study suggests that individuals with growth hormone receptor deficiency (GHRD), a rare genetic mutation also known as Laron syndrome, may have a lower risk of cardiovascular disease (CVD).

GHRD is characterized by an impaired ability by the body to use its own growth hormone; this leads to stunted growth, but it has been associated with an incredible 40% lifespan extension in mice, as well as reduced risk for age-related disease risks in mice [1]. However, its impact on cardiovascular health in humans has remained unclear, and there has been speculation that this longevity mutation may actually increase cardiovascular disease.

Longevity.Technology: These findings shed light on the potential interplay between growth hormone signaling and cardiovascular health. The lower risk factors for cardiovascular disease observed in individuals with GHRD suggest that the mutation not only affects growth but also confers protective effects against age-related cardiovascular decline.

From a geroscientific perspective, this research opens new avenues for understanding the molecular mechanisms underlying longevity and age-related diseases. It suggests that interventions targeting growth hormone signaling pathways may have broader implications for promoting healthy aging and reducing the burden of cardiovascular diseases – the world’s biggest killer. Further exploration of these pathways could lead to the development of novel therapeutic strategies for age-related cardiovascular conditions.

The study, recently published in Med, is the result of nearly two decades 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.

Over the past twenty years, Longo, Guevara-Aguirre and colleagues have investigated the health and aging of people with the gene mutation that causes GHRD. This mutation is rare, found in just 400 to 500 people worldwide, and it was discovered in a group of Ecuadorians whose ancestry can be traced back to people who fled Spain over three centuries ago, escaping the Inquisition. The mutation results in ineffective growth hormone receptors and causes a form of dwarfism.

Previous research by the team indicated that while GHRD/Laron syndrome inhibits growth, it also appears to lower the risk of several age-related diseases. Despite having a higher rate of obesity, Ecuadorians with GHRD have a significantly lower risk of cancer and type 2 diabetes. Additionally, they exhibit healthier brain function and perform better in tests of cognition and memory.

In the current study, the researchers examined cardiovascular function, damage,and risk factors in GHRD subjects and their relatives. They conducted measurements in two phases – one in Los Angeles and the other in Ecuador – involving a total of 51 individuals. Of these, 24 were diagnosed with GHRD, while 27 were relatives without the mutation serving as controls.

Key findings from the study included:

  • GHRD subjects exhibited lower blood sugar, insulin resistance and blood pressure compared with the control group.
  • They also had smaller heart dimensions and similar pulse wave velocity, indicating artery stiffness, but lower carotid artery thickness compared with control subjects.
  • Despite having elevated levels of low-density lipoprotein (LDL) cholesterol, GHRD subjects showed a trend for lower carotid artery atherosclerotic plaques compared with controls (7% vs. 36%).

“These findings suggest that individuals with GHRD have normal or improved levels of cardiovascular disease risk factors compared to their relatives,” said Longo, senior author of the new study.

“Although the population tested is small, together with studies in mice and other organisms this human data provide valuable insights into the health effects of growth hormone receptor deficiency and suggest that drugs or dietary interventions that cause similar effects could reduce disease incidence and possibly extend longevity [3].”

Photograph courtesy of Jaime Guevara-Aguirre and Valter Longo.
It shows Jaime Guevara-Aguirre (back left), Valter Longo (back right), and several of the Laron study participants at the USC Leonard Davis School of Gerontology in Los Angeles.

[1] https://pubmed.ncbi.nlm.nih.gov/10875265/
[2] https://www.cell.com/med/abstract/S2666-6340(24)00134-X
[3] https://gero.usc.edu/2024/04/26/people-with-rare-longevity-mutation-may-also-be-protected-from-cardiovascular-disease/