The Brain's Influence on Aging and Bone

As we age, our body slowly loses function--cell activity weakens, tissue loses strength, organs fail--until a point where biological function can no longer sustain life. But some people age more rapidly than others. Why is this? Genes certainly have a lot to do with how long you will live but is this process coordinated, and if so how and by what? An article published recently in Nature suggests that the aging process is actually programmed from within the brain, and it looks like we may be able to influence our longevity!

Chronic systemic inflammation is the predominant force behind the development of chronic disease. This type of inflammation is characterized by the elevation of the immune system's proinflammatory signaling molecules and the activation of a cell protein called NF-kB. This protein is found in every cell. When activated, NF-kB commands the cell's nucleus to turn on inflammatory genes within its DNA. The destructive forces of NF-kB-directed inflammation can be insidious, slowly but steadily burrowing into every organ of the body.

In a study conducted using mice, researchers Zhang et al. discovered that inflammation not only damages cells and tissues in the body but it also activates NF-kB in the hypothalamous of the brain. The hypothalamus links the nervous system to the endocrine system and is responsible for many metabolic processes attributed to the autonomic nervous system. When the body is stressed and inflamed, microglia cells within the hypothalamus sense this and trigger a release of the proinflammatory cytokine TNF-alpha which then stimulates NF-kB activation in surrounding neurons.

The TNF-alpha-induced NF-kB activation, in turn, inhibits the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. GnRH controls fertility through follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary gland, but the actions of GnRH don't stop there. This hormone is also involved in maintaining skin integrity, memory, and muscle and bone mass. When GnRH levels decline, we age...our skin thins, we begin to forget things, we loose muscle tone, and our bones become more fragile.

Chronic systemic inflammation, therefore, is behind this aging process and it is orchestrated by the hypothalamus. The domino effect goes something like this: stress, inflammation, oxidative stress...activation of NF-kB within microglia cells in the hypothalamus...increase TNF-alpha in the hypothalamus...increase NF-kB activity in neurons of the hypothalamus...decrease production of GnRH from these neurons.

Highlights of the author's conclusions:

• Aging is a life event that is programmed by the hypothalamus
• The hypothalamus is important for systemic aging and lifespan control
• The underlying causes of aging includes integration between immunity and the neuroendocrine system of the hypothalamus.
• Calming of the immune system's inflammatory response and GnRH restoration in the hypothalamus represent two potential strategies for combating aging-related health problems.

This discovery has the potential to help us all optimize our lifespan and fight aging-related health issues such as osteoporosis. By maintaining a healthy low-inflammatory diet, adding antioxidants such as alpha-lipoic acid, N-acetyl cysteine, berberine, and curcumin to the menu, and exercising regularly we can all reduce inflammation, limit oxidative stress, and live a longer, more productive and healthy life.

Zhang, G., et al. 2013. Nature. Hypothalamic programming of systemic ageing involving IKK-B, NF-kB and GnRH. doi:10.1038/nature12143.