Male DNA Key to Longevity

"This whole issue [research overturning the received wisdom of low height spurring longevity] has shocked us. It’s been a real disappointment."
Dr. Nir Barzilai, geneticist, Albert Einstein College of Medicine, New York

"If you look at dogs, flies, mice, whatever it is, smaller lives longer."
Dr.Gil Atzmon, geneticist, University of Haifa, Israel

Socializing in the city of Carmaux in the south of France. Researchers recently found that a genetic mutation may add about 10 years to men’s life spans. Credit Pascal Pavani/Agence France-Presse — Getty Images

The research undertaken by two geneticists who collaborate in their specialized research, appears to upset the generally agreed theory that smaller lives longer. Drs. Gil Atzmon at University of Haifa and Nir Barzilai at Albert Einstein College of Medicine in New York have between them studied the issue of longevity for many years. And they discovered the existence of a mutation, present in 12 percent of men who lived to reach and surpass age 100.

Growth hormone is produced in the brain and courses through the body where the hormone latches on to cells, binding to a surface molecule called a growth hormone receptor which can trigger cells to grow faster. The cells, for their part, may also release signaling molecules of their own, known as growth factors.

Their discovery of the mutation in question was described in Science Advances, and it also pointed out that there was no effect on women's longevity. A short list of gene variants have been shown to influence human longevity, the study of which lends hope to scientists that they may succeed in designing drugs based on knowledge gleaned through such studies, to effectively slow down the aging process.

Researchers begin with the understanding that in many species a relationship exists between the size of an animal and its span of life. They know that 25 percent of humans are endowed with mutation in the gene specializing in growth hormone receptors and that people with the mutation have variants in the shape of the working receptors, leading to studies that suggested the mutation might be responsible for children of lesser heights.

It was precisely the known link between size and longevity that inspired geneticist Gil Atzmon to contemplate whether how long people lived would also be influenced by mutations. Accordingly, with his colleague, Dr. Barzilai, the researchers undertook a sequencing of the gene for growth hormone receptors in 567 Jews over age 60 of Ashkenazi derivation, along with their children. This was  a group that Dr. Barzilai had been studying for years.

For his part, Dr. Atzmon examined the gene in people in the United States distinguished for their long lives, along with a group in France and from the Amish community. The total number of research subjects came to 814 people, and in all three groups the same effect was observed to exist by the researchers, where the mutation appeared to raise men's height by roughly 2.5 centimeters. A cascade of changes in growth-spurring signals in men's bodies triggered by the mutation is Dr. Barzalai's guess.

That process leaves cells less sensitive to low levels of growth hormones. Cells divide faster than those in men without the mutation, when growth hormone levels surge, however. In some biological process not yet understood, the receptor somehow amplifies the signal's growth which may spur boys' growth during adolescence. As the amount of hormone recedes when the boys reach adulthood, cells may divide more slowly and the production of growth-spurring molecules stop.

According to one theory, men with a mutation in their growth hormone receptor may place greater resources into their body repairs instead of into growth, and in the process slow the aging process. Which aligns with studies that suggest extra growth signals have the capacity to accelerate aging.
With the  use of a diabetes drug called metformin in animal studies the researchers produced promising results in attempting to mimic the effect of the mutation by reducing growth hormone levels in older people.