Mice may hold the key to longer life

Scientists from the University of Aberdeen, the Aberdeen-based Rowett Research Institute and the Medical Research Council (MRC) in Cambridge have made a major breakthrough in understanding how metabolism affects lifespan.

In a seven-year study of mice they found that those with the highest metabolic rate lived the longest, raising the prospect that the effect could be mimicked in humans.

Scientists have long thought that a high metabolic rate was linked to a shortened life-span. The present discovery turns this century old belief on its head and changes dramatically our understanding of the regulation of life-span.

Metabolism is the series of chemical changes necessary for the maintenance of life which take place inside the cells of the body. It is the means by which nutrients are broken down to smaller building blocks and chemical energy, which are used to make new body materials and to do work.

The researchers discovered that the most metabolically active 25% of the mice studied, far from having shorter life-spans, in fact lived 36% longer than the least active. If the same effects are mimicked in humans then the finding would imply that a higher metabolic rate could add an extra 27 years to the average human lifespan.

When the muscles of the most metabolically active mice were examined, they were found to contain factors that increased their metabolism by making it less efficient.

Although the scientists do not yet fully understand how these factors work, it is suspected that while they make the metabolism less efficient, on the positive side they reduce the generation of toxic by-products called "oxygen free radicals".

Free radicals can cause damage to the genetic information held in cells, but if fewer of them are produced, less cellular damage will take place, enabling the mice to live longer.

Professor John Speakman, leader of the Aberdeen research team, said: "We are really excited by this finding. Exactly how energy metabolism is linked to lifespan has been an issue of debate for decades.

"Our work provides a real step forward in our understanding of what is going on at the individual level, and has started to reveal the underlying mechanisms involved."

Professor Speakman added: "This is the first direct information on individuals within one species and the result is striking: living fast means dying old."

Dr Martin Brand, leader of the research team at the MRC Dunn Human Nutrition Unit in Cambridge added: "This finding gives us the first hint of a new way to try to achieve an increase in lifespan in humans by lowering our metabolic efficiency so that we burn more energy.

"The next step is to better understand the molecular basis of the effect in mice, to discover if we can exploit it in humans."

Professors Tim Cowen and Marc Tatar, Joint Editors-in-Chief of Aging Cell said: "The science of aging abounds with theories, which, when you get down to investigating them, turn out to be less easily justified than expected. This latest study has important implications for the idea that free radicals, generated by cellular metabolism, are key determinants of lifespan."

Professors Cowen and Tatar added: "We are excited to be publishing a paper from Professor John Speakman and his co-workers which suggests that when comparisons are made between animals of the same species, the theory that living fast - having a high metabolic rate - leads to dying young is not borne out."

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