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May 2, 2013

Researchers Identify The Key to Aging In The Hypothalamus




 Life Extension
Researchers may have found the body’s “fountain of aging”: the brain region known as the hypothalamus. For the first time, scientists at Albert Einstein College of Medicine of Yeshiva University report that the hypothalamus of mice controls aging throughout the body. Their discovery of a specific age-related signaling pathway opens up new strategies for combating diseases of old age and extending lifespan.








Anew study published in the journal Nature shows for the first time that manipulation of a brain chemical in a single region can influence lifespan.

The researchers at Albert Einstein College of Medicine measured the activity of a molecule called NF-κB in the brains of mice. Specifically they looked as levels of NF-κB in an area of the brain called the hypothalamus. This region is considered a deep old brain region and is involved in circadian rhythm, sleep/wake, hunger and thirst functioning.

“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,” said senior author Dongsheng Cai, M.D., Ph.D., professor of molecular pharmacology at Einstein. “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 the almond-sized structure located deep within the brain, is known to have fundamental roles in growth, development, reproduction, and metabolism.

Dr. Cai suspected that the hypothalamus might also play a key role in aging through the influence it exerts throughout the body.

NF-κB itself is a protein that controls DNA transcription and is involved in stress and inflammatory responses.

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They discovered that NF-κB levels became higher as the mice age, and the high levels were due to increasing age-related inflammation in the hypothalamus. When they blocked NF-κB activation, the mice lived longer. Increasing NF-κB activity reduced lifespan.

Furthermore inhibition of NF-κB produced dramatically reduced evidence of cognitive and motor decline in the animals suggesting the molecule stimulates the development of disease.

They were also able to increase the mean and maximum lifespan by 23% and 20% respectively in middle aged mice by inhibiting IKK-β, an enzyme that activates NF-κB.

It is also reported that NF-κB blocks gonadotropin releasing hormone (GnRH), and by giving mice GnRH aging was slowed.

This research is being hailed as a major breakthrough in aging and could quickly lead to real therapies to prolong human lifespan, which could even simply involve regular administration of GnRH.

It suggests that cumulative stress and inflammation in the body and the hypothalamus in particular signals increased production of NF-kB in the hypothalamus which then accelerates aging leading to decline and death. It also proves that a small crucial brain region may control aging in the whole body.

The authors conclude:
To summarize, our study using several mouse models demonstrates that the hypothalamus is important for systemic ageing and lifespan control. This hypothalamic role is significantly mediated by IKK-band NF-kB-directed hypothalamic innate immunity involving microglia–neuron crosstalk. The underlying basis includes integration between immunity and neuroendocrine of the hypothalamus, and immune inhibition and GnRH restoration in the hypothalamus or the brain represent two potential strategies for combating ageing-related health problems.


SOURCE  Extreme Longevity

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