High metabolic rate gives mice a longer life

Mice with sky-high metabolic rates live far longer than their sluggish cousins, UK researchers have found, raising the prospect that human lifespan might be lengthened with metabolism-boosting drugs.

Metabolic rate is the pace at which the body burns food to produce energy. John Speakman of the University of Aberdeen, UK, and his colleagues measured the metabolism of 42 mice, based on the amount of oxygen they consumed, and then waited until they died.

The group of animals with the highest metabolic rates lived over a third longer than the group with the lowest rates, they found, and had metabolisms that ran about 30% faster. If the same is true in humans, this means that people with a speedy metabolism might add an extra 27 years onto a typical 70-year lifespan.

The finding challenges a century-old theory that animals with higher metabolic rates die younger. This is based on observations that big animals with low metabolic rates, such as elephants, tend to outlive small, high metabolism ones, such as mice: hence the old adage, "live fast, die young."

While this overall trend may be true when comparing different species, the new study suggests it may be reversed for animals within one species. "It was a complete surprise," says Speakman.

The secret to longevity may lie inside mitochondria, the powerhouses of the cell that help to set the metabolic rate. Mitochondria use oxygen to 'burn' food molecules to produce chemical fuel that is used by the cell — but in the process they generate harmful free radicals that damage other molecules and are linked to ageing.

Speakman's team found evidence that mice with a high metabolic rate have more vigorous 'uncoupling proteins', which cause the mitochondria to generate heat instead of producing fuel. Since more of their energy escapes as heat, the mitochondria have to run at full speed in order to keep generating enough chemical fuel for the cell.

At the same time, the mitochondria may run more efficiently and release fewer harmful free radicals, hence slowing the ageing process. "That's when they run the cleanest," explains Wayne Van Voorhies, who studies ageing at New Mexico State University, Las Cruces.

Speakman now plans to test if a higher metabolic rate can prolong human life, but he cautions that a quick fix to ageing is unlikely to be just around the corner. Although drugs such as amphetamines are known to speed up metabolism, Speakman says that they may not simultaneously increase the activity of uncoupling proteins, the key to cutting free-radical production and thus potentially prolonging life.

Indeed, finding drugs that really do boost uncoupling proteins may be difficult, warns Van Voorhies. "You're really messing with some fundamental characteristics of [the cell]," he says.

References

1. Speakman, J.R. et al. Aging Cell, 3, 87, (2004). |Article|

© Nature News Service / Macmillan Magazines Ltd 2003

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