Prof. Gil Atzmon, longevity expert at University of Haifa and Albert Einstein College of Medicine in New York. Photo courtesy Israel21c

Genetic mutation explains why some men live to 100


Just as smaller animals of a given species generally live longer than their larger cousins, one might expect that taller humans are genetically programmed to sacrifice longevity for height.

But it’s not that simple.

A major multinational study of 841 men and women from across four populations found lower levels of insulin-like growth factor 1 (IGF-1) in men living to age 100 and yet most of them were taller than men in the younger control group.

The apparent explanation for this head-scratcher is that some long-lived men — and only men — have a genetic mutation that makes their growth hormone receptors more sensitive to the effects of the hormone. The cells absorb less growth hormone, yet protein expression is increased by several times.

This mutation seems to be responsible for their ability to live about 10 years longer than the control group of 70-year-old men without the mutation, even though they have a lower amount of growth hormone and are about 1.18 inches taller.

The lead author of the study is professor Gil Atzmon of Albert Einstein College of Medicine in New York and head of the Laboratory of Genetics and Epigenetics of Aging and Longevity at the University of Haifa. Since 2001, Atzmon has been studying the human genome and its impact on aging and longevity.

The researchers working with Atzmon looked at four elderly populations: 567 Ashkenazi Jews in the Longevity Genes Project at Einstein, 152 from a study of Amish centenarians, and the rest from an American cardiovascular health study and a French longevity study.

In 2008, the Longevity Genes Project found a genetic mutation in the IGF-1 receptor of some women, although it’s not the same as the one affecting men’s lifespans.

“We knew in the past that genetic pathways associated with growth hormone were also associated with longevity, and now we have found a specific mutation whose presence or absence is directly related to it,” Atzmon said.

“This study makes it an established fact that there is a relationship between the function of the growth hormone and longevity. Our current goal is to fully understand the mechanism of the mutation we found to express it, so that we can allow longevity while maintaining quality of life,” he added.

The 16 researchers involved in the study, published June 16 in Science Advances, are associated with institutions in Israel and France as well as in New York, Maryland, California, Vermont, Massachusetts and Washington.

While more research is needed to understand why the receptor mutation affects longevity and why it happens only in men, the study suggests that making a slight change in this specific piece of DNA could possibly make people live longer.

Although the presence of the mutation almost certainly ensured longevity, Atzmon stressed that many other factors affect longevity and that many men without the mutation also live to 100 and older.

Atzmon is one of the principal researchers in the Longevity Genes Project at Einstein, along with Israeli endocrinology specialist Dr. Nir Barzilai.

Their groundbreaking 10-year study of healthy Ashkenazi Jews between the ages of 95 and 112 and their children attempted to understand why humans don’t all age at the same rate, and why only one in 10,000 individuals lives to 100.

The centenarians were found to have genetic protective factors (“longevity genes”) that overcame factors such as diet and lifestyle.

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