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April 8, 2013

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As the infamous Randy Newman song goes, "Short people got no reason to live." Well, researchers now say some short people might actually be living longer, thanks to their genes. This ScienCentral News video explains how a gene that affects people's growth might also help control aging.

Adele Lerner, 101 years old
Terry Kaufman, Lerner's daughter
Nir Barzilai, Albert Einstein College of Medicine
Length: 1 min 28 sec
Produced by Sunita Reed/Jessica Tanenbaum
Edited by Sunita Reed/James Eagan
Copyright © ScienCentral, Inc.

Secrets of a Centenarian

101-year-old Adele Lerner lied about her age until she was in her 90's. But she didn't do so out of vanity. Rather, she didn't want people to view her as incapable of doing the things she wanted to do. When she finally told her children, Terry and Karen, that she was actually three years older than they had thought, they persuaded her to "come out of the closet."

Lerner explains what happened next.

"With the first interview in the Jewish newspaper everybody knew my life. I have no secrets. And I felt so good, because that was a bad secret for me," says Lerner.

Lerner, who started painting in her 50's, earned a bachelor's degree in fine arts at the age of 83. And she never stops learning. Since age 96, she talks daily to daughter Karen in California via web cam and instant messaging.

Lerner has sisters who lived into their 90's. She thinks she lived so long and stayed so healthy because of her faith, and her genes— which new research shows may account for both her longevity and her small size.

Short older woman with caption
Adele Lerner (right) with daughter Terry Kaufman
"I'm the shrimp of the family," Lerner explains. She's also the longest-lived.

Lerner was one of 450 people who've participated in a longevity study conducted by physician scientist Nir Barzilai and his team at Albert Einstein College of Medicine along with colleagues at UCLA and Johns Hopkins. The results showed that the fact that, at her tallest, she was a petite five feet, might also be linked to her longevity.

Previous studies in animals, such as mice, worms and flies, showed that mutations or variations in the genes affecting growth result in smaller animals with longer lifespan. In order to find out if these types of genetic variations correlate to height and longevity in people, Barzilai studied men and women of Ashkenazi Jewish descent who ranged in age from 95 to 108. He also studied their sons and daughters.

First he analyzed the blood levels, in the children, of a protein involved in growth called insulin/insulin-like growth factor I (IGFI). Levels of this protein correlate with the action of growth hormone. While the sons did not show variations from the comparison or control group, the daughters had 35 percent higher levels of IGFI. Daughters were also about an inch shorter than the control group. This indicated that the action of growth hormone was higher. So, why were the daughters shorter than the comparison group?

To answer that question, Barzilai's team looked at the gene that codes for IGFI receptors, the "landing spots" on cells that respond to IGF1, carrying out its orders. He studied the DNA of the seven shortest female centenarians in the group, and found that they had a high incidence of mutations in those genes. Barzilai also found that those mutations impaired the IGFI receptors, reducing the function of growth hormone.

While centenarians who had these mutations also had higher IGFI levels, "the growth hormone is not active and… the body is trying to compensate by producing more growth hormone, but of course not totally successful," Barzilai says.

"This really proves the concept that actually low growth hormone action is consistent with longevity, just like it happens everywhere in nature," he says. But he points out that this is just one gene in the growth pathway.

"This confirms the possibility that some centenarians get to this age because they have mutations in the IGF [growth pathway]. But it doesn't mean that all centenarians need to have this mutation in order to get to age 100," he adds.

In previous studies, Barzilai has found two other "longevity" genes which seem to increase the levels of "good cholesterol," or HDL. He believes that many other gene variations that contribute to long life will be found in future studies.

"I think that what we know from this technology so far is that we are going to have surprises. We are going to have genes that are associated with longevity or are protective against aging that we never thought before. That's going to be very exciting for us," says Barzilai.

Caution About Using Growth Hormone

But Barzilai cautions that his findings indicate that growth hormone injections used as an anti-aging treatment might backfire.

"We think that if you give growth hormone to an elderly subject that's gong to potentially be harmful, at least form the longevity point of view," Barzilai says. "Even if there are some good effects, we think that the fact that low growth hormone action is so consistent with longevity, growth hormone itself might not be."

He says the goal of his research is to find out how people can remain healthy as they grow older.

Regardless of whether we have protective genes, staying active mentally and physically is likely still the best bet. And Adele Lerner's example seems to suggest that staying mentally young is key.

"Age doesn't mean anything. You know, I am young in thought," Lerner says.

PUBLICATION: Proceedings of the National Academy of Sciences, March 4, 2008

STUDY TITLE: Functionally significant insulin-like growth factor I receptor mutations in centenarians

AUTHORS: Yousin Suh, Gil Atzmon, Mi-Ook Cho, David Hwang, Bingrong Liu, Daniel J. Leahy, Nir Barzilai and Pinchas Cohen

RESEARCH FUNDED BY: National Institutes of Health

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