A rare genetic mutation can result in individuals being shorter in stature, but it may also lead to a longer lifespan, shedding light on the mechanisms of aging.
A study published on April 26 in "Medicine" found that individuals carrying this genetic mutation exhibit several characteristics that can prevent heart disease, which is one of the most common causes of death. This may explain why their life expectancy exceeds that of the general population.
Researchers studied several Laron syndrome patients. Image source: Jaime Guevara-Aguirre and Valter Longo
For a long time, there has been speculation about the role of a signaling molecule called insulin-like growth factor-1 (IGF-1) in longevity. Studies have shown that artificially lowering IGF-1 levels through genetic modification and other means can lead to longer lifespans in various animals such as worms and mice. On average, centenarians also tend to have slightly lower IGF-1 levels.
In most species, IGF-1 promotes growth in youth and influences how cells utilize energy in later life. One perspective suggests a trade-off between investing energy in further growth and maintaining health.
Nir Barzilai from the Albert Einstein College of Medicine, who was not involved in the study, stated, "As you age and your body starts to weaken, you don't want to invest energy in growth but rather in preventing decline."
This trade-off can be studied in humans through a rare condition called Laron syndrome. Genetic mutations in these individuals lead to defects in their growth hormone receptors, resulting in stunted stature. Laron syndrome patients also have lower IGF-1 levels since the release of this compound is typically triggered by growth hormone.
It is estimated that there are 400 to 500 Laron syndrome patients worldwide. Due to the scarcity of individuals with this genetic mutation, it is currently unclear if they indeed live longer.
Supporting evidence comes from a 2011 study involving 90 Laron syndrome patients in Ecuador. The study found that Laron syndrome patients lived longer than expected compared to the general Ecuadorian population. Valter Longo from the University of Southern California stated, "They are overrepresented among the elderly."
In a recent study, Longo and colleagues compared 24 Laron syndrome patients from Ecuador or the United States with 27 unaffected relatives. Laron syndrome patients showed healthier indicators related to the heart, including blood pressure, blood sugar levels, and insulin sensitivity.
Individuals with this genetic mutation have higher levels of "bad cholesterol" - a compound known as low-density lipoprotein. This can increase the risk of arterial plaque formation, leading to heart attacks. However, only 7% of Laron syndrome patients had plaques, compared to 36% in their relatives. Longo mentioned, "This suggests that their arteries are not less healthy than those without the genetic mutation."
Alexei Maklakov from the University of East Anglia in the UK stated that this new finding supports the idea that somehow inhibiting the IGF-1 signaling pathway in later life can slow down the aging process. "It's a timing issue; you definitely don't want to do this during critical growth stages, but it might be beneficial later in life."
For more information, refer to the related paper: https://doi.org/10.1016/j.medj.2024.03.022
