A DUTCH woman who lived to 115 years old credited her longevity to pickled herring, refraining from smoking and limiting alcohol. But scientists are looking to the woman's genetic blueprints, hoping to uncover the secrets of successful aging.Any genetic secrets are still buried in the DNA that makes up the woman's genome, but it has become clear that she did not lack genetic variants that may predispose other people to heart disease, Alzheimer's and other aging-related illnesses, geneticist Henne Holstege of the VU University Medical Centre in Amsterdam said October 14 at the International Congress of Human Genetics. Instead, the woman may have carried variants that protected her from the ravages of age.Also, bigger, better human brains may be the result of a double dose of a gene that helps brain cells move around. At least twice in the past three million years, a gene called SRGAP2 has been duplicated within the human genome, says Megan Dennis of the University of Washington in Seattle, United States, in a study published in Nature.Also, new evidence suggests that many genetic variants linked to disease may play a role in regulating gene activity rather than altering the gene itself. In recent years, scientists have discovered genetic variants associated with a wide variety of diseases, but in most cases it has not been clear exactly how the variant leads to disease.What those protective variants might be remains a mystery. 'We cannot say anything about the genome pieces that have to do with longevity,' Holstege said. The researchers will have to compare the woman's genetic makeup with that of other extremely long-lived people, as well as average Joes and Janes, to find potential keys to long life.The woman, Hendrikje van Andel-Schipper, agreed to donate her body to science at age 112. At that time, Holstege's father, neuroscientist Gert Holstege of the University of Groningen, performed mental tests and found van Andel-Schipper to be at least as mentally sharp as a person nearly half her age.After van Andel-Schipper's death from a stomach tumour in 2005, researchers examined her brain and blood vessels for signs of disease that often accompany aging. They found nothing: She had no sign of the plaques or other degenerative proteins that build up in the brains of people with Alzheimer's disease, and her arteries were clog-free.Her case seemed to negate the idea that everyone develops dementia if they live long enough. 'Here was proof of principle that it doesn't have to happen,' Holstege said.Now researchers have compiled genetic blueprints from blood and brain cells of van Andel-Schipper (whom they refer to only as 'W115'). Analysis has begun to try to find genetic determinants of long life and to track the mutations that accumulate in a person's body over a lifetime.Dennis and her colleagues have now shown that extra copies of this gene may account for humans' thicker brain cortex, the brain's gray matter where thinking takes place.The team had previously discovered that SRGAP2 is one of 23 genes duplicated in humans but not in other primates. Dennis found that an ancient form of the gene, which is located on human chromosome 1, was partially duplicated on the same chromosome about 3.4 million years ago. That partial copy makes a shortened version of the SRGAP2 protein.Then, about 2.4 million years ago, a copy of the partial copy was created and added to the short arm of chromosome 1, Dennis reported October 13 at the International Congress of Human Genetics.But just having extra copies doesn't mean the gene is evolutionarily important. So Dennis and her colleagues examined the duplicate genes in more than 150 people and found that the copy made 3.4 million years ago is missing in some people. But the younger version of the gene has become fixed in the human population, meaning that absolutely everyone has it. Millions of years may seem like a long time, but it is actually quite speedy for fixing duplicated genes, Dennis says. The rapid assimilation could indicate that the gene is important in human evolution.Working with collaborators, the researchers have found that the shortened version of the SRGAP2 protein interferes with brain cells' ability to make projections called filopodia, which the cells use to move around. Reducing the number of projections streamlines the cells so that they can migrate further in the brain, perhaps allowing humans to build extra cortex layers, the team proposes.
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