06 May 2013

The source of aging

Hypothalamus is the key to aging

LifeSciencesToday by Albert Einstein College of Medicine:
Hypothalamus and Aging. Brain Region May Hold Key to AgingWhile the search for the "fountain of youth" continues, the "fountain of aging" – an area of the brain called the hypothalamus – may have already been found.

For the first time, scientists from the Albert Einstein Medical College of Yeshiva University (Yeshiva University) showed in mice that the hypothalamus controls the aging of the entire body. The discovery of a signaling pathway specifically associated with aging opens up new opportunities in the fight against age-related diseases and in increasing life expectancy.

The work of Zhang et al. Hypothalamic programming of systematic aging involving IKK-beta, NF-kB and GnRH is published in the online edition of the journal Nature.

"Scientists have long wondered whether different tissues of the body age independently of each other or whether this process is actively regulated by some one organ," says the head of the study, Professor of the Department of Molecular Pharmacology Dongsheng Cai, MD, PhD. "As our study makes clear, many aspects of aging are controlled by the hypothalamus. It is especially interesting that it is quite possible to change the signaling in the hypothalamus and thereby slow down the aging process and increase life expectancy – at least in mice."

The hypothalamus, a structure the size of an almond located deep inside the brain, is known to play a crucial role in growth, development, reproduction and metabolism. Dr. Tsai suggests that the hypothalamus may also play a key role in aging, affecting the entire body.

"As the body ages," explains the scientist, "it is possible to detect changes of an inflammatory nature in various tissues. Inflammation is also involved in the development of various age-related diseases, such as metabolic syndrome, cardiovascular and neurological diseases and many types of cancer."

Over the past few years, Dr. Tsai and his colleagues have shown that inflammation-induced changes in the hypothalamus lead to the development of various components of the metabolic syndrome.

To find out how the hypothalamus affects aging, Dr. Tsai decided to study hypothalamic inflammation, focusing on the protein complex – transcription factor NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells, a kappa-type light chain enhancer of activated B cells).

"Hundreds of molecules are involved in the development of inflammation, and NF-kB is right at the center of this regulatory map," explains Dr. Tsai.

In this study, he and his group showed that activation of the NF-kB pathway in the hypothalamus of mice significantly accelerates aging, as evidenced by various physiological, cognitive and behavioral tests.

"In mice, there was a reduction in skin thickness and a decrease in muscle strength and size, as well as learning ability – and all these are indicators of aging. Activation of this pathway contributed to systemic aging, which shortens life expectancy," Tsai comments.

On the other hand, the researchers found that blocking the NF-kB pathway in the hypothalamus of mice slows down aging and increases the average life expectancy of animals by about 20 percent compared to the control group.

Activation of NF-kV in hypothalamic neurons increases with age (left column), while the total number of neurons (middle column) and the total number of cells of all types (right column) in the hypothalamus is maintained at a relatively constant level in all age groups. (Nature)

In addition, the researchers found that activation of the NF-kB pathway in the hypothalamus causes a decrease in the level of gonadotropin-releasing hormone synthesized in it (gonadotropin-releasing hormone, GnRH, GnRH).

The entry of GnRH into the blood is usually associated with reproduction. Assuming that a decrease in GnRH intake from the brain into the bloodstream could contribute to the aging of the entire body, the researchers injected this hormone into one of the ventricles of the hypothalamus of old mice and observed striking results: injections of the hormone protected animals from impaired neurogenesis (the formation of new neurons in the brain) associated with aging. Daily administration of GnRH for a long period had a beneficial effect on old mice: in animals, age-related cognitive decline slowed down, probably as a result of a positive effect on neurogenesis.

According to Dr. Tsai, preventing the development of hypothalamus-induced inflammation and enhancing neurogenesis through GnRH therapy are two potential strategies for increasing life expectancy and treating age–related diseases. The method is already ready for licensing.

Portal "Eternal youth" http://vechnayamolodost.ru06.05.2013

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