Secrets of a century

Always wanted to know what your chances are to live to 100? The answer lies in your genes, or so researchers from Leiden and Delft, who are working together in the Medical Delta program on aging, believe. They are unravelling the genetics of longevity.


Some people are born lucky. Their genetic make-up gives them good prospects for a long and healthy life. That is beyond doubt. Much more elusive however is the question as to what extent individual gene variants contribute to or even predict longevity.

In 2010 a Science paper on longevity claiming to have an answer on that question caused quite an uproar. Scientists from the University of Boston had undertaken a genome-wide association study of exceptional longevity in 1055 centenarians and 1267 controls and reported that they had found 150 genetic variants that could be used to predict, with 77% accuracy, whether or not a person is genetically predisposed to living for a hundred years or longer. Some of these variants would give people a tenfold increased chance of seeing their hundredth birthday compared to an average person.

It all seemed too good to be true. And it was. The paper was retracted. The study’s centenarian cases and control samples were analysed in different labs and using different technologies. In other words, the researchers did a terrible job.

All the more reason why the article about longevity, with first author Marian Beekman of the molecular epidemiology lab of the Leiden University Medical Centre (LUMC), that appeared last month in the journal Aging Cell, was much anticipated. Led by the University of Leiden and the University of Bologna a European research consortium on aging performed the largest genome-wide linkage scan for longevity thus far. The research included 2118 sibling pairs aged between 89 and 107 years old that were enrolled in 15 study centres across 11 European countries as part of the so-called Genetics of Healthy Aging project.

The research-team identified four regions in the human genome that harbour genes responsible for the long life of the siblings. For these regions the siblings shared more genetic similarity than you would expect based on Mendels laws of inheritance only. The fact that the siblings inherited the same beneficial genetic variants in these regions may thus have contributed to their survival.

The researchers linked these regions to longevity. “By doing so we refined the search for healthy ageing genes from 20 thousand human genes to about 800”, says Prof. Eline Slagboom, head of the molecular epidemiology lab of LUMC.

So what does this mean for me? If I want to know what my chances are on seeing my hundredth birthday would it suffice to have my DNA sequenced and have the four regions of interest subsequently compared with those of people aged more than 100 years?

“Unfortunately not”, laughs one of the authors, PhD student ir. Erik van den Akker, of the section Pattern Recognition and Bioinformatics (EEMCS faculty) and LUMC. “The results we found are very nuanced. Something interesting is going on in those four regions, but now we have to figure out to what genes and mechanisms this hints. Only for one of the four regions we know which gene (the APOE gene) can be directly linked to longevity. That gene also happens to be connected to cardiovascular health and Alzheimer disease.”

Van den Akker and his colleagues believe there is a myriad of genetic variants within those four regions, many of which may be family specific and very rare, that play a role in longevity. Why they are specifically located in these four regions is not clear.

The Delft researcher is now taking a next step in the analysis of the long living families of the Leiden Longevity Study. He is analysing the complete genome sequence of 220 centenarian siblings that belong to the longest living families in this study cohort and he will zoom in more on the regions of interest.

M. Beekman, et. al., ‘Genome-wide linkage analysis for human longevity: genetics of healthy aging study‘, April 2013, Aging Cell

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