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Scientists Halt Aging in Mice by Tweaking Activity in Almond-Sized Brain Region

Update Date: May 01, 2013 01:37 PM EDT

Scientists have discovered for the first time that the body's aging switch may be located in the brain region that controls growth, reproduction and metabolism. 

The latest study, published online in the journal Nature, revealed that the brain's hypothalamus, an almond-sized brain region located just above the brain stem deep in the brain, may be the body's "fountain of aging".  

Researchers at Albert Einstein College of Medicine of Yeshiva University believe their discovery could lead to new treatments for extending lifespan and combating age-related diseases

"Scientists have long wondered whether aging occurs independently in the body's various tissues or if it could be actively regulated by an organ in the body," senior author Dr. Dongsheng Cai, a professor of molecular pharmacology at Einstein, said in a news release. "It's clear from our study that many aspects of aging are controlled by the hypothalamus. What's exciting is that it's possible - at least in mice - to alter signaling within the hypothalamus to slow down the aging process and increase longevity."

The hypothalamus is known to play essential roles in growth, development, reproduction and metabolism.  However, researchers suspected that the brain region might also play a key role in aging through the influence it has throughout the body.

"As people age, you can detect inflammatory changes in various tissues," Cai explained. "Inflammation is also involved in various age-related diseases, such as metabolic syndrome, cardiovascular disease, neurological disease and many types of cancer." Cai and his team previously found that inflammatory changes in the hypothalamus can trigger various components of metabolic syndrome, a combination of conditions that can lead to heart disease and diabetes.

To understand how the hypothalamus might trigger aging, researchers decided to study on hypothalamic inflammation by tracking the activity of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), a molecule that controls DNA transcription and is involved in inflammation and the body's response to stress.

After studying the activity of the NF-κB in the brains of mice, researchers found that the molecule becomes more active in the hypothalamus as the mouse grows older. Further analysis revealed that activating the NF-κB pathway in the hypothalamus of mice significantly accelerated the aging process in mice.

"The mice showed a decrease in muscle strength and size, in skin thickness, and in their ability to learn - all indicators of aging. Activating this pathway promoted systemic aging that shortened the lifespan," Cai explained.

However, blocking the NF-κB pathway in the hypothalamus of mouse brains slowed the aging process and increased median lifespan by about 23 percent and maximum lifespan by 20 percent.

Researchers say the findings suggested that NF-κB activity helps researchers determine when mice display signs of aging.

After further analysis, researchers found that activating the NF-κB pathway in the hypothalamus caused levels of gonadotropin-releasing hormone (GnRH), which is usually associated with reproduction, to drop. Researchers then injected the GnRH hormone into a hypothalamic ventricle of aged mice and found that the injections put the brakes on aging and triggered the growth of new brain cells. Researchers say the findings suggest that inflammation and stress are an evolutionary signal to the body to stop reproducing, which initiates the aging process.

Researchers say the findings suggest that preventing the hypothalamus from causing inflammation and increasing neurogenesis via GnRH therapy are two potential treatments for increasing lifespan and preventing age-related diseases.

David Sinclair, a molecular biologist at Harvard Medical School in Boston, Massachusetts, told Nature.com that the findings are "a major breakthrough in aging research".

Sinclair said the key finding is that inhibiting the effects of NF-κB produced anti-ageing effects even in middle age.

"If we're going to translate this research into medicines that can help people, clearly we cannot start very early in life," he explained. 

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