Dr. Michael Mullan M.D., Ph.D
President & CEO
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
Amyloid-Beta precursor protein (APP) gene which has shown to have a significant effect in those with Alzheimer’s disease
Research has shown that nearly two-thirds of dementia cases of patients over 60 in the Western Hemisphere are cases caused by Alzheimer’s disease. This correlation with age continues as the frequency of Alzheimer’s nearly doubles by five year increments after the age of 65.To gain a better understanding of this prevalence, scientists are looking into the amyloid-b precursor protein (APP) gene which has shown to have a significant effect in those with Alzheimer’s disease. Through their research, derived from 1,795 Icelandic citizens, scientists have discovered a mutation in the APP gene that safeguards individuals from cognitive deterioration and Alzheimer’s disease. Because mutations on this site (A673T allele) also prevents cognitive decline in patients without Alzheimer’s, this suggests that the two conditions may be controlled by or related through the same mechanisms.
Patients enrolled in this study were registered through the Memory Clinic at Landspitali University Hospital and the cognitive condition was assessed through the Minimum Data Set (MDS) for nursing homes. Genotypic data was then collects for the APP site A673T for all 1,763 patients. This data reveals that this site on APP is vital to the production of amyloid plaque, making it able to protect patients from the cognitive decline seen in Alzheimer’s and non-Alzheimer’s patients. These results make this mutation the first genetic variant discovered that can create a strong shield from Alzheimer’s disease. It also confirms the hypothesis that the pathogenesis of regular cognitive deterioration and Alzheimer’s disease may be partially related, suggesting that Alzheimer’s disease may be the driving force of the correlation between age and decline in cognitive function.
By Alec Waid, Intern Roskamp Institute