New Genetic Model Accurately Predicts Who's Likely to Live to 100

In 1997, Jeanne Louise Calment of France died at the age of 122, making her the oldest documented human to have ever lived. But is there something genetically unique about centenarians that enables them to age gracefully and relatively disease-free?

According to the results of a long-term study at Boston University School of Medicine, the answer is yes. People who live to be 100 years or older are rare, and only about 1 in 600,000 people in industrialized nations live that long.

As part of the New England Centenarian Study, a team of aging research specialists led by Paola Sebastiani and Tom Perls looked at 300,000 genetic markers in 800 centenarians and compared their profiles with those of random individuals. They then developed a genetic model that can compute an individual's predisposition to living a long life and found that centenarians shared a common genetic signature that could predict extreme longevity — with 77 percent accuracy. The findings represent a breakthrough in understanding how genes influence human life spans.

"Out of 100 centenarians we could correctly predict the outcome of 77 percent, while we incorrectly predicted the outcome of 23 percent," said Sebastiani. The researchers believe the 23 percent error rate can be attributed to genetic variance not yet known and included in the analysis, as well as other factors that influence longevity. "Making healthy lifestyle choices such as eating a well balanced diet or exercising regularly and avoiding exposure to tobacco plays an undisputed role in determining how each of us will age," said Andrew Sugden, international managing editor of Science.

Centenarians are a model of aging well, and 90 percent of people who reach this milestone are disability free at the average age of 93, Perls said. But he advised caution about the possibility of "testing" people to determine longevity, saying that much more study needs to be done regarding how health care providers and the research community guide individuals about what to do with the information they get. "I think a test for exceptional longevity is not quite ready for prime time," he said. "We're quite a ways from understanding what pathways governed by these genes are involved and how the integration of these genes, not just with themselves but with environmental factors, are all playing a role in this longevity puzzle."

According to Perls, future analysis of the results may shed light on how specific genes protect centenarians from common age-related diseases, such as dementia, heart disease, and cancer. "I look at the complexity of this puzzle and feel very strongly that this will not lead to treatments that will get a lot of people to become centenarians, but it could make a dent in the onset of age-related diseases like Alzheimer's," he said.

Chemical patterns on DNA mark out obesity genes

Your genes play a big part in determining your body shape, but that role may not have been set in stone when your parents' egg and sperm got together. It now looks like chemical changes that happen to genes over a person's lifetime may influence how fat they become, without altering their inherited DNA sequences.

This is the first time that prolonged chemical changes to genes during life have been implicated in obesity and body weight.

The findings add to the mounting evidence that it's not only genes that dictate important bodily traits – environmental cues and conditions may also affect such traits by altering gene activity. These "epigenetic" changes influence whether genes are on or off, but do not change the DNA sequence.

The latest findings relate to epigenetic changes which involve methylation, the process by which the addition of chemicals called methyl groups to DNA can turn genes on or off, or moderate a gene's activity by changing the way it is read.

Icelandic obesity

A team led by Andrew Feinberg of Johns Hopkins University School of Medicine in Baltimore, Maryland, and Daniele Fallin of the Johns Hopkins Bloomberg School of Public Health, also in Baltimore, mapped methylation in the DNA of 74 adults with a range of body types, looking for patterns that seemed likely to have been prolonged and set early in life, or even in the womb.

To do this, they first screened the volunteers' DNA in 1991, and picked out 227 regions with methylation patterns that varied between the individual members of the group by an unusually large amount. They then screened the same people in 2002 to distinguish which methylation patterns had not changed over the 11 years, reasoning that the variation in these patterns must have occurred early in life, then become fixed, having a persistent effect on traits such as body weight or intelligence.

Of the 227 methylated sites, 119 were found to be the same in 2002 as they had been 11 years earlier. Feinberg and Fallin then matched these groups to the body type of the individual. They found 13 methylated genes that were more likely to be present in the participants who were overweight or obese.

These chemical changes could have arisen in response to environmental conditions, such as the childhood diet of the individual or even of their mother during pregnancy.

"We don't know yet the degree to which genes and environment add up to give these stable methylation changes, but we believe both are important," says Feinberg.

Usual suspects

The 13 methylated genes include those that make metalloproteinase enzymes, which have already been implicated in obesity through studies on mice. Another, called PRKG1, plays a role when insects and nematodes forage for food.

The researchers caution that it is not yet possible to say whether the methylation changes are a result of environment influence, perhaps in the diet, or whether they are ultimately genetic because they are orchestrated by other genes.

But if specific methylated genes linked with obesity can be identified, they may provide new ways to screen people for risk of becoming overweight or obese. "The results do suggest the importance of including epigenetic analysis with genetic analysis in personalised medicine research to predict risk," says Feinberg.

"Relationships between epigenetic markers such as methylation patterns and particular disease or body states are hard to establish with confidence," says Bryan Turner, a geneticist at the University of Birmingham, UK.

New Measurement of Telomere DNA Could Help Identify Most Viable Embryos for IVF

Scientists from the University of Warwick and University Hospitals Coventry and Warwickshire NHS Trust, are the first to directly measure a specific region of DNA in human embryos. The length of this region could be a quality marker for embryonic development.

Researchers at the University of Warwick's Warwick Medical School and University Hospital, Coventry, have measured telomeres, regions of repetitive DNA at the ends of a chromosome which protect it from deterioration. Telomeres shorten each time a cell divides and when telomere length becomes critically short, the cells die.

The research, published in Molecular Human Reproduction Journal, suggests that telomere length is shortest in the early stages of an embryo's development, at around two days, and then lengthens just before implantation in the womb at five days. This lengthening may be essential for normal development, because short telomeres may not be enough to survive the many rounds of cell division that take place as embryos grow.

Lead authors Professor Geraldine Hartshorne, from the University of Warwick's Warwick Medical School, and Sarah Turner, from University Hospital , Coventry, said this discovery could have implications for IVF treatment. Professor Hartshorne said: "It has already been shown that artificially shortened telomeres cause problems in animal embryos. Human embryos are highly variable, and many of them cannot develop normally. We think that telomere length might one day be used to help diagnose which are the most viable embryos. We also know that telomeres shorten with oxidative stress, so telomere length might also provide a measure of the stressfulness of the culture systems that we use in IVF and their impact on embryos."

The research project used oocytes and embryos donated by patients undergoing IVF treatment. Only material that could not be used for the patients' own treatment was accessed for research. Sarah Turner said: These results have given us plenty of new questions as well as answers. We now need to find out why telomere length is relatively short in early development. Our next steps are looking at single sperm and eggs to work out where the telomere length in early embryos is coming from. "