HPC-UK Bitesize (Health): Age is Definitely a State of Mind

Ageing is a result of gradual and overall functional deteriorations across the body. We have an idea about many of the processes involved, however a recent study has postulated that a specific part of the brain is central to the rate at which ageing occurs throughout the body.

This shouldn’t surprise anyone who has done the HPC-UK Lean for Life program, as we discover throughout that the brain is the key player in pretty much everything. This piece of research also wasn’t a surprise to me, as I had learned this specific pathway of ageing described in the study almost a decade ago.*

The part of the brain in question is the hypothalamus, an almond-sized structure located deep within the brain, which is known to have fundamental roles in growth, development, reproduction, and metabolism. The lead researcher on the study, Dr. Cai, suspected that the hypothalamus might also play a key role in ageing through the influence it exerts throughout the body.

As people age inflammation gradually increases in various tissues. We know that inflammation is involved in various age-related diseases, such as metabolic syndrome, cardiovascular disease, neurological disease and many types of cancer. Over the past several years, Dr. Cai and his research colleagues showed that inflammatory changes in the hypothalamus can give rise to various components of metabolic syndrome (a combination of health problems that can lead to, amongst a growing list, heart disease and diabetes).

To find out how the hypothalamus might affect ageing, 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, but NF-κB is a key regulator of the cascade.

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. This resulted in the mice showing a decrease in muscle strength and size, in skin thickness, and in their ability to learn -- all indicators of ageing. Activating this pathway promoted systemic ageing that shortened the lifespan.

Conversely, Dr. Cai and his group found that blocking the NF-κB pathway in the hypothalamus of mouse brains slowed ageing and increased average 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 increased levels of the hormone in the hypothalamic ventricle of aged mice and discovered that the hormone protected them from the impaired neurogenesis (the creation of new neurons in the brain) associated with ageing. The aged mice who received the daily GnRH augmentation for a prolonged period demonstrated benefits that included the slowing of age-related cognitive decline, probably via the result of neurogenesis.

Reference:

Guo Zhang, Juxue Li, Sudarshana Purkayastha, Yizhe Tang, Hai Zhang, Ye Yin, Bo Li, Gang Liu, Dongsheng Cai. Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature, 2013; DOI: 10.1038/nature12143

*Many of the programs offered by HPC-UK cover this process, especially the specific Anti-Ageing and Brain programs