Life Extension Update
Mechanism defined for calorie restriction's preventive benefit in Alzheimer's disease
A report that will appear in the July, 2006 issue of the Journal of Biological Chemistry contributes evidence to the hypothesis that restricting calories and carbohydrates may prevent Alzheimer's disease by stimulating longevity-associated molecular mechanisms in the brain.
Professor of Psychiatry and Neuroscience and Director of the Mt Sinai School of Medicine's Neuroinflammation Research Center Giulio Maria Pasinetti, MD, PhD, and colleagues administered a low calorie, low carbohydrate diet to mice and observed a reduction in amyloid beta peptides, which lead to the formation of plaques in the brains of Alzheimer's disease patients. Other mice given higher calorie, high fat diets experienced an increase in the peptides. The reduction in amyloid beta occurring in the calorie restricted mice coincided with an increase in brain levels of SIRT1, a member of a family of proteins called sirtuins that are associated with longevity. SIRT1 may initiate the activation of alpha-secretase, an enzyme that can inhibit the generation of amyloid beta. Dr Pasinetti told Life Extension, “When we expressed SIRT1 in brain cells [in vitro] that produce beta amyloid, we found that SIRT1 expression prevented beta amyloid generation.”
"Both clinical and epidemiological evidence suggests that modification of lifestyle factors such as nutrition may prove crucial to Alzheimer's disease management," Dr Pasinetti stated. "This research, however, is the first to show a connection between nutrition and Alzheimer's Disease neuropathy by defining mechanistic pathways in the brain and scrutinizing biochemical functions. We hope these findings further unlock the mystery of Alzheimer's and bring hope to the millions of Americans suffering from this disease."
Compelling and growing evidence links inflammation and oxidative stress to Alzheimer's disease. According to the inflammation theory (discussed in dozens of recent clinical trials), inflammatory cytokines gather at the neurons of people who have Alzheimer's. These cytokines set off an inflammatory cascade. The inflammation generates high levels of free radicals that contribute directly to the formation of beta-amyloid plaques. The result is more inflammation, free radicals, and beta-amyloid plaques. Iron has also been linked to the generation of free radicals. Studies have shown that free iron accumulates on the surface of dying neurons, where it generates oxygen-derived free radicals that hasten the spread of the disease (Mandel S et al 2006).
Other possible causes include high levels of homocysteine in the brain and specific nutrient deficiencies. Although these ideas are still developing, they have opened up exciting new targets for therapy. In clinical studies, the most cutting-edge researchers are turning to therapies such as anti-inflammatory nutrients, antioxidants that reduce oxidative stress, and metal chelating agents (such as green tea) that reduce the levels of free iron in the brain.
Ashwagandha is a medicinal plant used in India to treat a wide range of age-related disorders. Its most remarkable effect may involve its ability to preserve the health of the aging brain. Research indicates that ashwagandha extract is capable of halting and even repairing damage to brain cells in an experimentally induced model of Alzheimer's disease (Kuboyama T et al 2005). Scientists in Japan induced Alzheimer's-type brain cell atrophy and loss of synaptic function in mice by exposing them to the toxic protein beta-amyloid (Kuboyama T et al 2005). In laboratory experiments in India in 2004, researchers discovered that ashwagandha root extract inhibits acetylcholinesterase in much the same way as the prescription drug donepezil, which is currently used in the treatment of Alzheimer's disease (Choudhary MI et al 2004).
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