Could a Short Stature Mutation Combat Aging? New Research Says Yes

Written by Camilla Jessen

Apr.29 - 2024 8:26 AM CET

Photo: USC Leonard Davis
Photo: USC Leonard Davis
Rare mutation that causes short stature may shed light on ageing.

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A rare genetic mutation linked to Laron syndrome, which typically results in shorter stature, might also provide clues about aging and how to live longer by offering protection against heart disease. This potential benefit is brought to light in recent studies that investigate how a specific hormone influences aging.

Insights from Laron Syndrome

People with Laron syndrome have a particular gene variant that not only impacts their height but also seems to increase their lifespan compared to the average person. This advantage is largely due to characteristics that guard against heart disease, one of the top causes of death globally.

The hormone at the center of these studies is called insulin-like growth factor-1 (IGF-1), which has been associated with longevity.

Research on different animals, including worms and mice, has shown that lowering levels of IGF-1 through genetic changes can lead to longer lives. This observation is also true in humans, especially in centenarians, who generally have lower levels of this hormone.

The Trade-Off Hypothesis

IGF-1 plays two roles: it helps promote growth when we are young and influences how cells manage energy as we age.

Scientists believe that there is a balance between using energy for growth and using it to keep the body healthy as it gets older.

"As you get older and start to wear down, you don’t want your body to focus on growth; you want it to focus on maintaining health," explains Nir Barzilai from the Albert Einstein College of Medicine in New York, who was not involved in the study.

Laron syndrome offers a unique way to study this idea because of its specific effects. The condition is caused by a mutation that affects how growth hormone receptors work, leading to shorter stature and lower levels of IGF-1 due to reduced stimulation from growth hormone.

While clear evidence that people with Laron syndrome live longer is scarce due to their small numbers—estimated to be between 400 and 500 worldwide—a 2011 study of 90 Ecuadorians with the condition suggested that they tend to live longer than the general population.

Study Findings and Implications

More recently, Valter Longo from the University of Southern California and his team compared 24 people with Laron syndrome to 27 of their relatives who do not have the mutation.

They found that those with the syndrome had better heart health indicators, like blood pressure and blood sugar levels. Even though they had higher levels of “bad cholesterol,” only 7% of people with the syndrome had artery plaques, compared to 36% of their relatives.

Although the small number of participants means these results could be due to chance, the data suggest that the arteries of people with Laron syndrome are not necessarily in worse condition than those without the mutation. Other research has shown that people with this syndrome are less likely to develop cancer and tend to experience less mental decline as they age.

These findings support the idea that adjusting IGF-1 signaling pathways in later life could help slow down aging, according to Alexei Maklakov from the University of East Anglia.

"Timing is crucial," he notes. "You wouldn’t want to alter these pathways during important growth periods, but later in life, it might be possible to do so to potentially slow the aging process."

This research not only deepens our understanding of how genetics can influence health and longevity but also suggests the possibility of developing treatments that could replicate the beneficial effects seen in people with Laron syndrome.

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