Fasting Protects the Brain

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Science  31 May 2013:
Vol. 340, Issue 6136, pp. 1017
DOI: 10.1126/science.340.6136.1017-b

Fasting has been shown to slow aging in a number of species. Caloric restriction acts on many different cell types and tissues and, importantly, also on the brain. There, it leads to a slowing-down of age-associated pathologies, such as brain atrophy or loss of synaptic plasticity. Moreover, in several animal models, a reduced consumption of calories seems to protect against cognitive deficits such as memory loss. However, it is not known whether caloric restriction can delay the beginning of neurodegeneration. The mechanisms underlying these observations are also largely unclear. In experiments using genetically modified mice, Gräff et al. found that caloric restriction effectively delayed the onset of neurodegeneration and preserved structural and functional synaptic plasticity as well as memory capacities. Fasting activated the expression and activity of the nicotinamide adenine dinucleotide (NAD)–dependent protein deacetylase SIRT1, a known promoter of neuronal life span. Surprisingly, this effect of reduced consumption of calories could be mimicked by a small-molecule SIRT1-activating compound. Mice treated with this substance recapitulated the beneficial effects of caloric restriction against neurodegeneration-associated pathologies. If this mechanism also applies to humans, SIRT1 may represent an appealing pharmacological target against neurodegeneration.

J. Neurosci. 33, 8951 (2013).

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