Gene variant found that may help people live to be 100

Hold the butter! The genetic secrets of centenarians are starting to be unravelled and they hint that low cholesterol plays a role in their unusual longevity.

"This is one of the first studies to detect rare genotypes in these exceptional individuals," says Joo Pedro de Magalhes of the University of Liverpool, UK, who was not involved in the research.

It is thought that genetics accounts for up to 30 per cent of the variability in human lifespan. But so far just two genes have been linked to longevity, and neither has a large influence creating a genetic puzzle sometimes called "missing heritability".

Suspicion has been growing that rare mutations are behind longevity. But these get missed by standard genetic studies, which sequence small snippets of DNA for known variants rather than scouring the full genome to find unknown ones.

To look for unknown rare mutations, Timothy Cash of the Spanish National Cancer Research Centre in Madrid and his colleagues sequenced the entire exome the protein-coding part of DNA of three Spanish centenarians and four of their long-lived siblings. These were compared with the exomes of 800 people, many of whom could be assumed to have average lifespans, as only one in 5000 people live to 100.

One gene apolipoprotein B had rare mutations in all three long-lived families that were less common in the 800 controls. The protein made by this gene helps carry "bad cholesterol" in the blood, high levels of which lead to heart attacks. It is possible that the mutations reduce levels of this bad cholesterol.

The team is now investigating whether the centenarians' cholesterol levels bear out this theory. If they do, "this would definitely reinforce the idea that cardiovascular health is an important factor in overall ageing", says Cash.

Intriguingly, previous work has shown that another gene for which there is strong evidence for a role in human lifespan is apolipoprotein E, which also helps transport cholesterol. However, the beneficial variants of this gene also reduce the risk of Alzheimer's disease, which is usually thought to be the main reason behind their effects on longevity.

Another gene that has recently been implicated in longevity is FOXO3A, which may affect people's sensitivity to insulin.

Journal reference: Aging Cell, doi.org/vfv

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Gene variant found that may help people live to be 100