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Longevity primarily hereditary in extremely long-living families

Newswise Jan 09, 2019

Longevity is heritable, but that primarily applies to persons from families where multiple members are among the top 10% survivors of their birth cohort. The key to a long life can probably be found in the genes of these families. These are the conclusions of researchers at Leiden University Medical Center, together with their colleagues from Nijmegen and the US, in an article in Nature Communications.

The researchers reached their conclusions after studying the genealogies of 314,819 people from 20,360 families dating back to 1740. The research data were obtained from two large datasets, one at the University of Utah in the US and one in the Dutch province of Zeeland. Authors of the study include Niels van den Berg, a doctoral student studying molecular epidemiology, and Eline Slagboom, professor of molecular epidemiology, both at Leiden University in the Netherlands, and University of Utah professor Ken Smith, director of the Utah Population Database.

“We observed...the more long-lived relatives you have, the lower your hazard of dying at any point in life,” said van den Berg, lead author. “For example, someone whose parents are both ‘top survivors’ has a 31% lower hazard of dying than someone of the same age without such parents.

“Moreover, that person’s hazard of dying is reduced, even if the parents themselves did not live to be extremely old but aunts and uncles were among the top survivors,” van den Berg said. “In long-lived families, parents can therefore pass on longevity genes to their children, even if external factors prohibited them from reaching the top survivors.”

Different populations but the same pattern

The researchers identified similar results in Utah and Zeeland, despite the very different environmental circumstances. In Zeeland, people stayed in the same place for a long time, while in Utah there was a high influx of migrants during the 19th century. Moreover, during the study period in Zeeland, there was a lack of clean drinking water, whereas in Utah fresh water was available from the mountains for some communities.

“Despite these differences we reached the same conclusions regarding the inheritance of longevity in families,” van den Berg said. “This reinforces our idea that there really are longevity genes to be discovered in humans.”

Searching for genes in the wrong group

The search for genes associated with human longevity has been ongoing for a long time but those genes turned out to be much more difficult to discover than genes for diseases, for example, according to Slagboom, research coordinator.

“This research has led us to be far stricter in selecting the people in whom you have to look for those genes,” Slagboom said. “If you investigate a random group of people aged over 100, however exceptional they may be, it’s highly likely that many of them do not in fact belong to a family in which longevity is heritable. Their age is probably a matter of chance, the result of a healthy lifestyle or healthy circumstances for example during childhood, and isn’t, therefore, reflected in their DNA.”

Smith said that the findings underscore the importance of constructing high-quality family trees that “allow us to observe complete life-spans of individuals over generations and in diverse locations.

“With these carefully constructed data sets, we observed the same family patterns of extreme longevity observed across diverse circumstances which demonstrate the value of deep genealogies for identifying specific families that potentially harbor genes for exceptional survival,” Smith said.

The message for fellow researchers is, therefore, that when investigating longevity, they should examine people from families where multiple members are among the top 10% of survivors of their birth cohort.

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