About 50 percent of human lifespan is determined hereditarily, writes an international team from researchers on Thursday Science. It was previously estimated that up to a quarter of lifespan is heritable, but these estimates often did not take into account external causes of death, such as accidents, infectious diseases and natural disasters. As a result, the role of genes remained underexposed. Once corrected for these causes of death, it turns out that genes play twice as important a role in lifespan and aging than previously assumed.
For research into the heritability of lifespan, twin research is the gold standard, says Joris Deelen, associate professor at the Leiden University Medical Center and involved in the study. “Identical twins are genetically identical. By looking at differences in mortality in twins who grow up together or apart, you can estimate the relative role of heredity and environment.”
But to make these kinds of estimates correctly, you have to work with a population that has now died. The cohorts that researchers can use for this are therefore at least a century old, sometimes even a hundred and fifty years old, and therein lies a methodological pitfall, says Deelen. “Due to poor hygiene and living conditions, many people died at a young age from childhood diseases and infections. These are causes of death for which the risk of death does not change with increasing age, so they say little about the heritability of longevity. Previous studies on this subject did not look at the cause of death, which is why they estimated the role of heredity at 10 to 25 percent: a systematic underestimate.”
It is not surprising that previous studies ignored the causes of death: in most datasets these were not recorded. The research team therefore developed new mathematical models that could include estimates of the various causes of death. They made a distinction between external causes of death such as accidents and infections, and causes of death that are driven by the aging process, such as non-communicable diseases.
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Data from existing databases showed that external causes of death are a constant factor in lifespan. This makes it possible to systematically exclude them from existing twin studies. They applied their model to a Danish and a Swedish study and saw that there was a stronger connection between the lifespan of twins who grew up together. A similar effect showed when they applied the method to an American database of brothers and sisters of centenarians. When they combined the results and then also corrected to exclude younger deaths, the researchers saw that around 50 percent of lifespan is genetically determined. Heredity seems to play a particularly important role in mortality from cardiovascular diseases and dementia, while mortality from cancer is more dependent on chance and environmental factors.
The outcome of the research is at odds with the growing skepticism about the role of genetics. In recent years, the idea has prevailed that genes contribute little to aging, says Deelen. “As someone who researches the genetics of aging, I am regularly asked whether this is useful at all. But the outcome of this new research shows that there is plenty of reason to do research into this.”
Scientists who study aging or diseases will start taking genetics a lot more seriously, according to two independent editors Science in a commentary on the study. In addition, lifestyle interventions may have less effect than thought, they write. But according to Deelen it is important not to go too far with that idea. “The other 50 percent is still determined by your environment: where you live, your lifestyle, whether you smoke, and your access to care. So you should not think that you cannot influence your lifespan.”
The research also shows that it is worthwhile to look for genetic variants that play a fundamental role in aging. Exactly which genes contribute to longevity is still largely unknown, says Deelen, but he hopes that his current research will change that. “In some families, people appear to be ‘genetically enriched’ and they live exceptionally long. This may be partly due to mutations in certain genes that combat inflammation and cell aging. By understanding how and why these people grow old healthily, we could imitate this effect with a lifestyle intervention or medicine and thus hopefully ensure that other people can also live healthily for longer.”
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