A new study by researchers at the Albert Einstein School of Medicine dramatically underscores the potential role of the NF-kB protein in aging. NF-kB is a master protein which controls many inflammatory chemicals throughout the body. Researchers at the Roskamp Institute have studied NF-kB for many years as a potential way of controlling chronic inflammation which accompanies aging and underlies conditions such as Alzheimer’s disease. This new study points to a part of the brain as regulating the aging process. The current view of aging generally suggests that enzymes, DNA, proteins and other constituents of the body essentially “wear out” with age, accumulating damage due to environmental insults until they no longer function properly. This new study suggests something quite different, namely that a part of the brain called the Hypothalamus deliberately induces aging throughout the body. It has been suggested that one reason why the brain might take such drastic action is to inhibit reproduction past a certain age. This suggestion is highly speculative at this stage, but the data offered by the Albert Einstein researchers suggests that, with age, increased NF-kB activity triggers degeneration in both the brain and other areas of the body. The researchers showed that as mice aged, they increasingly expressed NF-kB in the part of the brain that is normally responsible for the production of reproductive and growth hormones. The researchers artificially manipulated NF-kB activity using genetic techniques and showed that reducing NF-kB activity was associated with better performance in cognitive tests, greater muscle strength and greater bone mass and skin thickness. Conversely, exacerbation of NF-kB activity increased all of these peripheral signs of aging, as well as reducing cognitive abilities. Furthermore the research suggested that microglia (the inflammatory cells resident in the brain) are the originators of the NF-kB activity and this spreads to nearby neurons, including those responsible for growth and reproductive hormones. These findings are of direct significance to work at the Roskamp Institute as researchers there have shown that increased NF-kB collates strongly with Alzheimer’s pathology and pathology of other central nervous system disorders. Moreover, they have worked extensively on ways to reduce NF-kB activation, particularly using the naturally occurring compound Anatabine.  Roskamp Institute researchers have shown in multiple preclinical studies of neuroinflammation (such as Alzheimer's, traumatic brain injury and Multiple Sclerosis) that Anatabine (supplied by RockCreek Pharmaceuticals) has potent anti-inflammatory properties. This new finding suggests that NFKB inhibitors might also have a role in decelerating aging. In fact,  preliminary studies at the Roskamp Institute suggest that mortality in mice with Alzheimer pathology is reduced by Anatabine treatment. Additional studies are needed to clarify whether Anatabine might reduce the Hypothalamic inflammation and increase the release of hormones that oppose aging.

Dr. Michael Mullan M.D., Ph.D
President & CEO
Roskamp Institute
 
 
With the increased life expectancies, the number of the elderly over the age of 90 is rising worldwide. A paper published in the journal, Neurology, focused on a specific study of dementia rates in the very old. Performed in California with over 900 participants, it has shown that there are differences based on gender in risks of dementia or Alzheimer’s disease (AD) for men and women over the age of 90. For women, the chances of developing dementia double by five year increments after 90 years of age, which confirmed the fact that women over 90 are at a greater risk of dementia than men in the same age group. In dementia populations over 90 years of age, only 28 percent of men have dementia, whereas 45 percent of women suffer from the disease. However, the study has revealed that women who had consistently used their brains during their life and had received a higher education had less of a chance of developing dementia compared to those who did not have that benefit. The knowledge that women are at a greater risk than men in developing heart disease or stroke with age, both of which act as independent risk factors for dementia and intensify the symptoms of AD, may be beneficial in understanding why women over 90 are at more risk. In addition, research has shown that Alzheimer’s is also negatively affected by vascular factors, as the work Roskamp Institute scientists’ showed that vasculature damage increases in presence of amyloid. Vascular risk factors are found more frequently in women as they age, and patients in the earlier stages of AD receive a greater neurological impact than normal individuals from vascular damage. Roskamp Institute scientists are using these pieces of information along with other knowledge in order to develop new treatments for dementia.

For more details on this study, as well as additional information on Alzheimer’s disease, please visit

http://www.roskampinstitute.us/articles/archives/43

http://www.rfdn.org
http://www.roskampinstitute.us
http://www.michaelmullan.us
http://www.michaelmullangroup.com

Wendy Liu

July 27, 2012