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Anti-Aging Gene Loss Possible Culprit in Elderly Blindness

Nady Golestaneh  “We found a number of important functions Klotho provides in the human retina, which leads us to believe that the gene is crucial to the health of this light-sensitive tissue,” said Nady Golestaneh, lead author of the study.

October 10, 2013 – Loss of an anti-aging gene triggers retinal degeneration in mice and may contribute to age-related macular degeneration, according to a team of Georgetown University Medical Center (GUMC) researchers.

The researchers published their study Oct. 9 in The Journal of Neuroscience, the official journal of the Society for Neuroscience. They say their findings may one day lead to gene or cell therapy for age-related macular degeneration, the major cause of blindness in the elderly.

The scientists demonstrated that the anti-aging gene Klotho plays a key role in maintaining the health of the mouse and human retina.

Crucial to Health

In animal studies, GUMC researchers found that the loss of Klotho’s ability to do its job leads to characteristics observed in both kinds of macular degeneration — wet and dry — that are seen in humans.

“We found a number of important functions Klotho provides in the human retina, which leads us to believe that the gene is crucial to the health of this light-sensitive tissue,” says the study’s lead author, Nady Golestaneh, assistant professor of ophthalmology, neurology, biochemistry and molecular & cellular biology.

Klotho, a hormone synthesized and secreted by some organs and tissues, is being studied worldwide for its anti-aging properties.

A Japanese researcher discovered 15 years ago that when Klotho is mutated, a mouse that should live two years survives only two months. Transgenic mice that overexpress the Klotho gene have a longer than expected lifespan. 

More Research Needed

Among the Georgetown researchers’ findings are that Klotho increases the activity of genes that synthesize the light-absorbing visual pigments in retinal cells.

“We believe Klotho might be an interesting therapeutic target for age-related macular degeneration,” Golestaneh says. “Gene therapy or cell therapy might be able to induce new expression of Klotho in the aging retina.”

But before these strategies can be tested, she says research must be conducted that quantifies the decline of Klotho expression in human eyes and directly links that dysfunction to macular degeneration.

The study’s first author is Maria Kokkinaki from GUMC’s ophthalmology department.

The department of ophthalmology at GUMC provided support for this research. The researchers used the shared resources facility of Georgetown Lombardi Comprehensive Cancer Center (grant #P30 CA051008) to conduct some of their work.

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