Scientists identify part of brain that may hold the key to aging

Even as the fountain of youth proves elusive, scientists at the Albert Einstein College of Medicine at New York City’s Yeshiva University may have discovered its exact opposite, the region of the brain that holds the key to aging. Researchers at the institute conducted studies in mice that revealed the hypothalamus potentially controls whole-body aging. In humans, the hypothalamus is an almond-sized structure located at the base of the brain. It controls many key processes in the body. The scientists identified a specific signaling pathway associated with aging. This discovery can open up opportunities to modify the pathway and combat diseases of old age, and ultimately, extend a person’s lifespan. “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 study author Dongsheng Cai, M.D., Ph.D., professor of molecular pharmacology at Einstein. The hypothalamus plays an important role in growth and development, metabolism, and reproduction. The study authors felt that given this wide-ranging influence, it would not be surprising if the hypothalamus plays a key role in aging. As a person ages, inflammatory changes occur in the different organs of the body. Inflammation is associated with many of the most common age-related diseases that afflict humans, such as cardiovascular disease, metabolic syndrome, and neurological disorders. Dr. Cai and his colleagues suspected that inflammation regulated by the hypothalamus could be responsible for the various components of metabolic syndrome, a collection of health conditions that can lead to diabetes and heart disease. There are hundreds of molecules involved in inflammation. To study the role of hypothalamus-mediated inflammation, the scientists focused on the nuclear factor kappa-light-chain-enhancer of activated B cells, or NF-κB in short. This is a collection of proteins that plays a key role in the regulation of inflammation. The group demonstrated that when the NF-κB pathway was activated in mice hypothalami, there was a significant acceleration of the aging process, as measured by different cognitive, physiological, and behavioral tests. “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,” says Dr. Cai. Interestingly, the team found that blocking the same pathway in mouse brains delayed the aging process. Also noted was a significant increase in median longevity (approximately 20 percent) compared to controls. “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.” – Donghseng Cai, M.D., Ph.D. So, how does activation of the NF-κB pathway speed up aging? The researchers found that when this pathway in the hypothalamus is activated, there is a reduction in the synthesis of gonadotropin-releasing hormone (GnRH). GnRH is a hormone that is produced by the hypothalamus and is linked to reproduction. The scientists suspect that lower levels of GnRH could contribute to whole-body senescence. Interestingly, when the researchers injected GnRH into the hypothalami of aging mice, they observed a striking effect. The GnRH injections had a protective effect that prevented impaired neurogenesis. Neurogenesis is the formation of new brain cells and is often impaired during old age. With continued daily hormone injections over an extended period, the benefits were even more obvious with a slowing down of cognitive decline, possibly due to neurogenesis. The study has demonstrated that preventing inflammation regulated by the hypothalamus and improving neurogenesis through GnRH therapy are potential strategies to delay aging, treat age-related health conditions, and increase lifespan.