Huntington's Disease Gene and Enhanced Longevity

Published at PLoS Genetics, an unexpected longevity gene: "Expansion of a stretch of glutamines near the amino-terminus of huntingtin (htt), the protein product of the IT15 gene, is a deleterious mutation that causes Huntington's disease (HD). Here we show, in contrast, that deletion of htt's normal polyglutamine stretch (deltaQ-htt) is a potentially beneficial mutation that can ameliorate HD mouse model phenotypes when deltaQ-htt is expressed together with a version of htt with the HD mutation. In addition, deltaQ-htt expression can enhance longevity when expressed in either an HD mouse model or in non–HD mice. deltaQ-htt's effects on both lifespan and HD model phenotypes are likely due to an increase in autophagy, a major recycling pathway in cells that is involved in the turnover of cellular components, and aggregated protein. Based on our results, we suggest that development of therapeutic agents that can stimulate autophagy may help both in treating neurodegenerative disorders like HD and also in increasing longevity."


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