Will you live to 100? Last year, scientists published a study proposing a “genetic signature” that could help answer that question. But they retracted the paper when critics discovered errors that invalidated the results. Now the team is back with a revamped study that proposes a different signature; it’s less predictive in most people but, they say, it still underscores that your chance of living a very long life has a powerful genetic component.
The flap began 18 months ago, when biostatistician Paola Sebastiani, geriatrics specialist Thomas Perls, and their colleagues at Boston University reported in Science that they had identified 150 gene variants that, taken together, could predict with 77% accuracy one’s chance of becoming a centenarian. The work was immediately criticized by geneticists who said it incorrectly inflated the importance of a number of gene variants, making the signature look more powerful than it really was. Sebastiani and Perls subsequently said they had not realized that the microarray technology they used to identify the various gene variants had certain limitations. Last July, acknowledging that they had failed to take those into account, they retracted the paper.
At the time, Sebastiani and Perls promised to redo the work and publish any new results. They recruited additional researchers from Yale University who have expertise in analyzing genomewide association studies. While the research team analyzed the original study group of just over 1000 very elderly people—mostly centenarians but some in their 90s—and about 1200 controls, they added another small cohort of 60 extremely elderly individuals, whose median age was 107.
The genetic findings from this reanalysis were less startling than the original ones: Unlike in the Science paper, in which several specific gene variants carried a significant association with a 100-year-plus life span, here almost no variants were very significant on their own. Only when the 281 gene variants were taken all together was there a signature with enough statistical power to predict old age, the team reports this week in PLoS ONE. In most of the cohorts studied, the predictive power was also less, about 60% compared with 77% in the Science work. However, the researchers did find that the older the cohort, the more likely the genetic signature was to correctly predict extremely long life—predictability reached 85% with the oldest group. “It’s very consistent with the idea that the heritability of longevity increases with age,” because the power of genes becomes ever more important, Perls says.