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We show that the progression of neuropathological (formation of huntingtin inclusions and apoptotic protease activation), behavioral (motor dysfunction), and metabolic (glucose intolerance and tissue wasting) abnormalities in huntingtin mutant mice, an animal model of HD, are retarded when the mice are maintained on a dietary restriction (DR) feeding regimen resulting in an extension of their life span. DR increases levels of brain-derived neurotrophic factor and the protein chaperone heat-shock protein-70 in the striatum and cortex, which are depleted in HD mice fed a normal diet. The suppression of the pathogenic processes by DR in HD mice suggests that mutant huntingtin promotes neuronal degeneration by impairing cellular stress resistance, and that the body wasting in HD is driven by the neurodegenerative process. Our findings suggest a dietary intervention that may suppress the disease process and increase the life span of humans that carry the mutant huntingtin gene.<\/jats:p>","DOI":"10.1073\/pnas.0536856100","type":"journal-article","created":{"date-parts":[[2003,3,4]],"date-time":"2003-03-04T18:36:00Z","timestamp":1046802960000},"page":"2911-2916","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":349,"title":["Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice"],"prefix":"10.1073","volume":"100","author":[{"given":"Wenzhen","family":"Duan","sequence":"first","affiliation":[{"name":"Laboratory of Neurosciences and Comparative Medicine Section, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224; Department of Human Genetics, Emory University, 615 Michael Street, Atlanta, GA 30322; and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihong","family":"Guo","sequence":"additional","affiliation":[{"name":"Laboratory of Neurosciences and Comparative Medicine Section, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224; Department of Human Genetics, Emory University, 615 Michael Street, Atlanta, GA 30322; and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Laboratory of Neurosciences and Comparative Medicine Section, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224; Department of Human Genetics, Emory University, 615 Michael Street, Atlanta, GA 30322; and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melvin","family":"Ware","sequence":"additional","affiliation":[{"name":"Laboratory of Neurosciences and Comparative Medicine Section, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224; Department of Human Genetics, Emory University, 615 Michael Street, Atlanta, GA 30322; and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Jiang","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Neurosciences and Comparative Medicine Section, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224; Department of Human Genetics, Emory University, 615 Michael Street, Atlanta, GA 30322; and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark P.","family":"Mattson","sequence":"additional","affiliation":[{"name":"Laboratory of Neurosciences and Comparative Medicine Section, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224; Department of Human Genetics, Emory University, 615 Michael Street, Atlanta, GA 30322; and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"341","published-online":{"date-parts":[[2003,2,14]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.15.5733"},{"key":"e_1_3_3_2_2","first-page":"513","volume":"7","author":"Andrew S E","year":"1993","unstructured":"S E Andrew, Y P Goldberg, B Kremer, H Telenius, J Theilmann, S Adam, E Starr, F Squitieri, B Lin, M A Kalchman, et al. 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