2008-09-03

Men who have two copies of a "long life gene" triple their odds of living nearly a century, according to a study published today.

The advantage is all down to having two "letters" of the six billion letter human genetic code that are the same and the scientists who report the find believe that this kind of understanding could have important implications for living longer and lowering the risk for age-related disease and disability.

The gene linked with better health and a longer life is called FOXO3A and although similar genes have been shown to prolong life span in other species, this is the first time that FOXO has been linked directly to longevity in humans.

The findings from the Hawaii Lifespan Study will be published in the Proceedings of the National Academy of Sciences by Drs Bradley Willcox, Tim Donlon, David Curb and colleagues at the Kuakini Medical Centre, Honolulu, and colleagues in Japan.

They conclude the link is "strong, highly significant."

They have been following the health of 8,000 Japanese-American men who have had periodic health exams since the mid 1960s and, says Dr Willcox, no other study has tracked such a large group of men for this long, in such detail.

One location on the gene FOXO3A stood out as having a link with enjoying old age.

Genetic code is written in an alphabet of four chemical units, strung together to make the double helix molecule of DNA. Of the four letters in the alphabet (A, T, C, G), the majority of participants in the study had the T letter at a key location in the gene. However, those who had G at this location had better health at the date of the original exam.

Each gene comes in two copies and the team found the longevity effect of this letter was additive: those with one copy doubled their odds of living an average 98 years, with some living as long as 106 years.

Men who had two G copies did even better and almost tripled their odds of living nearly a century, and were markedly healthier at older ages, in terms have having less heart disease, stroke and cancer "We screened 213 of the long-lived participants' DNA and 402 of the average-lived, focusing on five genes," explained Dr Willcox.

These genes were selected for good reason because they involved in the insulin pathway and signalling, which studies of other animals have shown is linked with longevity, for instance through the influence of a gene called DAF-16 in the case of nematode worms.

"We then calculated how the DNA bases found at three locations on each gene were correlated with a comprehensive set of health criteria including chronic diseases, disability and insulin levels. What we found was very surprising and exciting."

While non-genetic factors, including diet, physical activity, health habits, and social influences are important, up to half of the variation in human lifespan might be explained by genetic differences.

However, studies of candidate "longevity-associated" genes in humans, "longevity genes," have generally been disappointing. Few replications have been observed across populations, with the exception of the APOE gene.

The team says that studies of FOXO genes and their effect on ageing should now be extended to other populations, such as Caucasians.

Carriers of the G version are more common in whites and blacks than Japanese, according to the Haplotype Map data from the Human HapMap project, a sister project to the Human Genome Project, that looks at variation within the human genome in four main populations - blacks, whites, Japanese and Chinese.

"FOXO3A does not appear to account for the Japanese or Okinawan longevity advantage (we looked at both populations - no differences)", said Dr Willcox, "but it could help explain longevity advantages within different human populations."

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