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The Live Longer Diet, Part 1: Eat Fewer Calories

October 6, 2009
As far back as the 1930s scientists showed that reducing the calorie intake of laboratory rats while maintaining sufficient quantities of vitamins, minerals and other nutrients can have health benefits. Calorie restriction appeared to increase the lifespan of the animals and evidence also suggests that it can have health benefits for people, though increasing longevity is still unclear. Now scientists have found that they can extend the lifespan of mice by up to a fifth and reduce the number of age-related diseases the animals suffer by blocking a key molecular pathway that mimics the health benefits of reducing calorie intake and suggests that drug treatments for aging and age-related diseases are feasible. In research primarily funded by the Wellcome Trust, Professor Dominic Withers and colleagues from the Institute of Healthy Ageing at University College London have discovered changes in the aging process in a strain of knockout mice unable to produce a particular protein known as S6 Kinase 1 (S6K1). S6K1 is involved in the body’s response to changes in levels of the food that we eat. Such nutrient sensing systems are crucial in enabling the body to respond appropriately to changing food levels in terms of growth and reproduction and also, it seems, aging. Deleting the S6K1 protein in mice has a wide range of health benefits, which appear to mimic the action of calorie restriction. "Blocking the action of the S6K1 protein helps prevent a number of age-related conditions in female mice," explains Professor Withers. "The mice lived longer and were leaner, more active and generally healthier than the control group. We added ‘life to their years’ as well as ‘years to their lives.’" (Their male counterparts showed some of the health benefits, but little difference in lifespan, though the reasons for these differences are unclear.) On average, the female mice lived for 950 days, over 160 days longer than the control group. Further studies showed that the beneficial effects of blocking S6K1 were mediated via increased activity of a second molecule, AMPK, which has been called a master “fuel gauge” as it regulates energy levels within cells. In particular, it is activated when cellular energy levels fall, as calorie intake is reduced.