Calorie Restriction Prevents Neurodegenerationby Jennifer Gibson, PharmD | June 14, 2013
Calorie restriction could be more than a weight loss technique. It may prevent nerve cell loss in the brain, and even contribute to increased lifespan and delayed aging. A new study published in The Journal of Neuroscience tested these hypotheses and discovered a potential target for drug therapy that could prevent diseases such as Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease.
Researchers at the Massachusetts Institute of Technology conducted a series of experiments on mice that had been engineered to undergo rapid neurodegeneration. To test the effects of calorie restriction, half of the mice were fed normal diets and half of the mice received only 70% of the calories of the normal diet. After three months, the researchers evaluated the learning and memory skills of all the mice. The mice that ate a normal diet showed significant decreases in learning and memory, while the calorie-restricted mice showed no deficits.
On further examination of the brains of the mice, the researchers discovered that the mice in the calorie-restricted group showed less nerve cell loss than the control group. The discovery focused on an enzyme named Sirtuin 1 (SIRT 1), which is expressed as a result of calorie restriction. In a second phase of experiments, the researchers administered a pharmacological dose of a SIRT 1-activating compound to a new set of mice, which were also engineered to experience rapid neurodegeneration. These mice received a normal diet during the course of the experiment. However, just like the calorie-restricted mice, after 3 months, they showed no learning or memory losses. Overall, the researchers concluded that nerve cell loss can be prevented, even without calorie restriction.
Calorie restriction, which is a regimen of reduced caloric intake without malnutrition, has long been associated with increased longevity and delayed aging processes in many mammal experimental models. Calorie restriction mitigates the onset and progression of age-related diseases by improving cellular resistance to stress, enhancing synaptic plasticity, and improving cognitive performance through nutrient-mediated cascades and signaling processes. Sirtuins are believed to play an active role in this process, conferring protective effects against cancer, diabetes, and cardiovascular disorders, as well as neurodegenerative diseases.
Though experiments to date have mostly been conducted in rodent and non-human primate models, pharmacological modulators of sirtuins, even without calorie restriction, could prevent age-associated diseases and possibly delay normal aging processes. It remains to be seen if simply reducing calorie intake by 20-30% could end the search for the elusive fountain of youth, but promising research is underway that may eventually clarify the mechanisms involved in aging and neurodegeneration, as well as the effects that nutrition has on both processes.
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Duan W, & Ross CA (2010). Potential therapeutic targets for neurodegenerative diseases: lessons learned from calorie restriction. Current drug targets, 11 (10), 1281-92 PMID: 20840070
Fusco S, & Pani G (2012). Brain response to calorie restriction. Cellular and molecular life sciences : CMLS PMID: 23269433
Gräff J, Kahn M, Samiei A, Gao J, Ota KT, Rei D, & Tsai LH (2013). A Dietary Regimen of Caloric Restriction or Pharmacological Activation of SIRT1 to Delay the Onset of Neurodegeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience, 33 (21), 8951-60 PMID: 23699506
Hursting SD, Smith SM, Lashinger LM, Harvey AE, & Perkins SN (2010). Calories and carcinogenesis: lessons learned from 30 years of calorie restriction research. Carcinogenesis, 31 (1), 83-9 PMID: 19969554
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