Amazing Science

"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."

To find out how the hypothalamus might affect aging, Dr. Cai decided to study hypothalamic inflammation by focusing on a protein complex called NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells). "Inflammation involves hundreds of molecules, and NF-κB sits right at the center of that regulatory map," he said.

In the current study, Dr. Cai and his team demonstrated that activating the NF-κB pathway in the hypothalamus of mice significantly accelerated the development of aging, as shown by various physiological, cognitive, 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," he said.

Conversely, Dr. Cai and his group found that blocking the NF-κB pathway in the hypothalamus of mouse brains slowed aging and increased median longevity by about 20 percent, compared to controls. The researchers also found that activating the NF-κB pathway in the hypothalamus caused declines in levels of gonadotropin-releasing hormone (GnRH), which is synthesized in the hypothalamus. Release of GnRH into the blood is usually associated with reproduction. Suspecting that reduced release of GnRH from the brain might contribute to whole-body aging, the researchers injected the hormone into a hypothalamic ventricle (chamber) of aged mice and made the striking observation that the hormone injections protected them from the impaired neurogenesis (the creation of new neurons in the brain) associated with aging. When aged mice received daily GnRH injections for a prolonged period, this therapy exerted benefits that included the slowing of age-related cognitive decline, probably the result of neurogenesis.