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Boston, MA – March 12, 2007 – An animal's metabolic rate does not determine how long it will live, disproving the age-old theory that metabolic rates determine longevity and rate of aging. The study, led by Joao Pedro de Magalhaes from Harvard Medical School, is reported in the latest issue of the Journal of Gerontology: Biological Sciences.

The reason why mice age and die within four years while dogs are old in their second decade of life and humans can live over a hundred years has puzzled scientists for decades, if not centuries. One of the oldest and most popular explanations is the idea that short-lived animals like mice and shrews have high metabolic rates and thus accumulate molecular damage faster than animals with lower metabolic rates, such as elephants. "Even now it's one of the most cited explanations for why different species age at different rates," says de Magalhaes. The new study, however, disproves this simple, even intuitive explanation by finding no correlation between metabolic rate and longevity using data for several hundred species, the largest dataset ever employed in such an analysis.

The study also takes advantage of contemporary statistical tools that allow researchers to eliminate the confusing effects of phylogeny and body size. "We know bigger animals live on average longer and have a lower metabolic rate," says de Magalhaes. "It is thus not surprising that early studies found an association between lower metabolic rates and longevity, but this was caused by the confusing effects of body size. When we statistically corrected for the effects of body size to focus solely on the association between metabolic rate and longevity we found no correlation." Previously, some species of bats and birds had been shown to be exceptions of this "rate of living" theory by having high metabolic rates and long lifespans. "We knew we wouldn't find a perfect correlation between metabolic rate and longevity, but to find no correlation at all in hundreds of primates, rodents and other mammals, and birds was surprising. At least in warm-blooded animals, metabolic rate does not appear to be a factor in longevity and aging."

Not only the study disproves the "rate of living" theory, but it also raises doubts regarding another popular theory of aging: the free radical theory of aging, which argues that damage caused by toxic by-products of oxygen metabolism called reactive oxygen species accumulates with time resulting in aging. Because metabolic rates were estimated from oxygen consumption at rest, the study also raises questions of whether damage caused by reactive oxygen species plays a role in differences in longevity between species. "All things being equal, one would expect animals with a higher oxygen consumption to produce more reactive oxygen species and age faster, so in that sense our results clash with the free radical theory. However," de Magalhaes warns, "we know that not all things are equal. For example, there could be differences in antioxidant levels that we did not take into consideration."

The study does not completely disprove the "live fast, die young" concept, though. A strong correlation was found between the timing of development, growth, and reproduction and lifespan. "Humans take longer to reach sexual maturity than mice, so we knew beforehand that these life-history traits are proportional to each other, but our results show a much stronger correlation than previously reported, even after correcting for body size and phylogeny. What this means is that, for instance, when developmental timing is extended by evolution, so is longevity." The question remains of whether the timing of development, growth, and reproduction could be related to longevity and pace of aging. "Nobody knows for sure," de Magalhaes says, "but there does appear to be some kind of timekeeper. Rather than believe in two timekeepers, one for development and one for aging, I would be more inclined to think that there is one timekeeper for both aging and development."

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