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Increasing Mammalian Lifespan, One Gene at a Time

New research has shown that lowering the activity of a gene called mTOR dramatically increased the average lifespan of a group of mice and allowed them to maintain high function in several—although not all—tissue and organ systems that typically decline with age. Found in mammals, the mTOR gene has been implicated in such key processes as metabolism and aging. However, the mechanism of how mTOR reduction affects lifespan and tissue aging has not been fully understood. Previous studies showing that mTOR is involved in metabolic functions indicated that this gene may be connected with the increased lifespan associated with caloric restriction. In this study, researchers bred a group of mice to have genetic alterations that reduced their mTOR levels. Compared to normal mice, these mutant mice had an increased lifespan of around 20 percent, showed reduced signs of aging in many organ tissues, and, as they aged, retained more balance, grip strength, and cognitive abilities like learning and memory. Mice with reduced mTOR protein also appeared to have fewer malignant tumors than normal mice. These effects of mTOR reduction did not appear to result from altered metabolism, since mice with less mTOR had similar metabolic profiles compared to normal mice. However, these benefits did not come without a price: mTOR-deficient mice contracted more serious infections as they aged and had more pronounced bone deterioration than their normal counterparts. Together, these results suggest that tissue aging may occur on related, but separate, “clocks” or be subject to other distinct biologic regulation compared to aging of an entire organism. Further research into the mechanism of how mTOR reduction affects the body is ongoing and may guide future therapies to increase both lifespan and “health span” in humans.


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