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Calorie Restriction with Optimum Nutrition Forum
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CRON4healthyfuture
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 Posted: Sat Jun 03, 2006 5:21 am Post subject: CR activates SIRT1 and steers APP to non-amyloidgenic form |
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This is an interesting paper. These scientists placed female mice on a diet that had a 30% reduction in calories, and watched as SIRT1 expression increased and NAD+ increased. In contrast, NAM (nicotinamide) decreased.
Furthermore, they found that alpha-secretase activity was increased during CR. This is important because the protein that ultimately forms the plaques in Alzheimer's disease is formed from a precursor protein that can either be processed by a good secretase or a bad secretase. Alpha-secretase is the good one, and so it will disfavor the development of Alzheimer's disease.
They also found that in the presence of Rho-kinase (ROCK) activity, alpha-secretase was inhibited. This implies that ROCK activity is incompatable with the health-promoting effects of CR in neurons.
All in all, a fascinating piece of work!
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| "Most importantly, we report that the predicted attenuation of -amyloid (A) content in the brain during CR can be reproduced in mouse neurons in vitro by manipulating cellular SIRT1 expression/activity through mechanisms involving the regulation of the serine/threonine Rho kinase ROCK1, known in part, for its role in the inhibition of the non-amyloidogenic -secretase processing of the amyloid precursor protein (APP). Conversely, we found that the expression of constitutively active ROCK1 in vitro cultures significantly prevented SIRT1 mediated response, suggesting that -secretase activity is required for SIRT1 mediated prevention of AD-type amyloid neuropathology. Consistently we found that the expression of exogenous human (h)SIRT1 in the brain of hSIRT1 transgenics also resulted in decreased ROCK1 expression and elevated -secretase activity in vivo. These results demonstrate for the first time a role for SIRT1 activation in the brain as a novel mechanism through which CR may influence AD amyloid neuropathology. The study provides a potentially novel pharmacological strategy for AD prevention and/or treatment." - June 2, 2006 J. Biol. Chem |
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