Zhang and colleagues from the Department of Molecular Pharmacology, Albert Einstein College of Medicine, New York, in a study published in the journal Nature this week (May 1st), have found a way to prolong the life of mice, both male and female, by regulating the levels of the hormone gonadotropin-releasing hormone (GnRH), which is normally regulated by the hypothalamus. These findings show how age-related diseases, such as Alzheimer’s, diabetes, osteoarthritis etc. could be prevented.
“It supports the idea that aging is more than a passive deterioriation of different tissues. It is under control, and can be manipulated,” says Dongsheng Cai, who led the study.
There is evident link between areas in the brain and aging from experiments in fruitfly Drosophila melanogaster and the worm Caenorhabditis elegans. In these experiments, the lifespan of these laboratory models was increased by manipulating certain neurons, which subsequently altered protein pathways in the brain cells.
In this new study, scientists have uncovered a chain of events that takes place in the hypothalamus of mouse brains. First, they found that the activity of NF-κB (a complex of proteins which is involved in the regulation of expression of particular genes of the immune system in all cells of our body) in the hypothalamus is proportional to the age of mice. The hypothalamus is a small, almond-sized region in our brain with a variety of functions (control of body temperature, hunger, fatigue, sleep, to name a few) via the synthesis and secretion of neurohormones. Then, they created three groups of middle-aged mice and in the first group they inhibited NF-κB, in the second group they activated NF-κB, while the third was the control group. Then all mice were fed normally. The results were astonishing, the group with inhibited NF-κB lived longer (>200 days than the control) and exhibited much less age-related characteristics while the group with activated NF-κB lived much less. The role of NF-κB needs special attention as it is involved in carcinogenesis. The results were similar when IKK-β, an activator of NF-κB, was blocked without any side effect in brain function.
“Through activating or inhibiting immune pathway IKK-b and NF-kB in the hypothalamus of mice, we were able to accelerate or decelerate the aging process, leading to shortened or increased lifespan,” state the authors.
What IKK-β and NF-κB do in our brains? The researchers found that expression of GnRH, which has roles in reproduction and regulates sex hormones, was blocked when IKK-β and NF-κB were hyperactivated. And when they injected this hormone in the hypothalamus of old mice, but also in other parts of the body, they were surprised to see that aging defects were reversed.
The authors also stated: “Our findings provide a proof of principle to the hypothesis that aging is a life event that is programmed by the hypothalamus.”
Have we found the youth pill? Definitely not! Despite the fact that the lifespan of mice was extended, they eventually died. And would this work also in humans? We do not know that yet.
But “If validated, the results could have important implications for our understanding and treatment of age-related diseases, particularly those linked to inflammation” said Professors Dana Gabuzda and Bruce A. Yankner from Harvard Medical School, who did not participate in the study. How GnRH functions exactly in the body is something that has to be rigorously studied. And “Given the many effects of these hormones, however, their clinical use in diseases of aging, such as diabetes, Alzheimer’s and heart disease, will need to be carefully studied,” Yankner said to The Guardian.
