In Iron Man 3, botanist, Rebecca Hall, developed Extremist which harvested the immense hidden power of the human brain to regenerate tissues, creating a virtually immortal supervillain and his army of fire-breathing minions. In reality, this dream of turning the tap on for our internal “Fountain of Youth” may not be too far-fetched after all: Scientists think they might have uncovered the biological command centre for ageing in the brain.
As we get older, all our organs start to deteriorate across the board like time worn spare parts. It’s possible that this happens independently for each organ and randomly. But animal studies suggest that parts of the brain might help to coordinate this body-wide decline. And scientist, Dongsheng Cai, from the Albert Einstein College of Medicine suspects that the nut-sized hypothalamus sitting right at the floor of the brain might be the secret button to push to unleash the “Fountain of Youth”.
Hardly bigger than an almond, the hypothalamus is a 24-hour brain control centre that helps keep our body in stable homeostasis. It uncodes constant information and feedback about the state of our body to coordinate the release of various hormones regulating many vital non-voluntary functions such as body temperature, thirst, hunger and sleep cycles. By tinkering with specific protein signalling in the hypothalamus, Cai and co. managed to speed up or slow down the ageing process in mice!
His team of researchers found that the NF-kB protein became more active in the hypothalamus of mice as they got older. By blocking this chemical early on in life, the scientists could increase the longevity of these mice by a fifth. Better still, those extra months were healthier ones: These mice had stronger muscles and bones, they performed better in learning and memory tests, and had healthier skin than controls. Conversely, when the levels of NF-kB were tuned up, the opposite was true. The rodents’ bodies declined and they died more quickly.
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As if is prolonging lifespan isn’t cool enough, these results highlight an important link between ageing and the immune system as well. Over several years, Cai and his colleagues showed that chronic inflammation in the hypothalamus can give rise to various components of metabolic syndrome too – a combination of health glitches, like diabetes, that paves the path to heart disease and stroke. Although inflammation involves hundreds of molecules, the NF-kB protein (a key responder of the immune system) seems to sit right at the centre of that regulatory map.
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Further investigation also showed that NF-kB lowered levels of GnRH, a central sex hormone produced by the hypothalamus that influences the development of sperm and eggs *surprise, surprise*. To find out more about this bizarre connection between our reproductive system with ageing, the scientists gave old mice daily jabs of GnRH. And this too, helped maintain their youthfulness and extended the animals’ lives. It even triggered fresh brain neurons to regrow – not only back in the hypothalamus, but also in other areas like the hippocamus (which is involved in memory).
This work of Cai et al. raises the tantalising prospect of new drugs that would allow us to actively put the brakes on the natural ageing process, fulfilling our dreams of eternal youth and triumphing over serious and common age-related diseases such as diabetes, heart problems, and Alzheimer’s. That is…when we finally solve the increasingly complex puzzle between the immune system, reproductive axis, and the brain, with the hypothalamic cerebral “pacemaker” in the middle of it all.
– By Gene Yeo
*This article has been selected Editor’s Choice for May 2013*