They are:

• ABO Determines blood group

• CDKN2B Helps regulate cellular life cycles


• SH2B3 Has been shown to extend lifespan in fruit flies

• One of the HLA genes, which are involved in how the immune system recognises the body’s own cells

Uncovered by searching the genomes of centenarians, the genes join a variant of APOE, which increases the risk of Alzheimer’s, as the bits of our genome most clearly associated with longevity. They’re tantalising clues to uncovering the mystery of why we age, and could help us find ways to prevent age-related diseases.

“I’m motivated because I really don’t understand why we get old,” says lead author Stuart Kim at Stanford University. “What is the clock that gives us 80?”

Gene trawl

Studies of identical twins suggest that genetic make-up has a significant influence on lifespan. It is common for siblings of the same family to live very long lives. “Those sorts of things argue persuasively that about 20 per cent of lifespan is genetic, possibly more for living to be extremely old,” says Kim.

But which genes are responsible? Several studies have looked for variations that are more common in long-lived people, but until now, only APOE consistently came up.

For example, in 2014, Kim published a study comparing the genomes of 17 supercentenarians – people aged 110 and over – with those of the general population. The study included a 116-year-old woman who was the world’s oldest living person at the time. He hoped the supercentenarians might share a rare variant that explained their tenacity but nothing turned up, and the media announced the death of the “longevity gene”.

Zoning in

This time Kim had more success. He expanded his search to include 800 people over 100 and about 5000 over 90 – but narrowed the focus to genes known to influence age-related diseases. His idea was that this would point the way towards common mechanisms associated with ageing.

He was right. Of the four new genes and APOE that showed up in the search , each has a variant that can reduce or increase a person’s chances of reaching 100. The variations are common in the general population, but centenarians seem to have fewer “bad” variants.

“It’s an elegant and refreshing approach,” says Henne Holstege from the VU University Medical Center in the Netherlands, who also studies supercentenarians.

Lifespan prediction

“It’s the first time someone has shown that particular disease [variants] are depleted in centenarian populations,” says Timothy Cash of the Spanish National Cancer Research Centre in Madrid. “It points to important processes that are impaired in ageing populations.”

Predicting people’s lifespan based on their genes remains a distant dream, however. “I don’t think we’ll ever have concrete genetic determinants that will allow us to say this person is going to live to be 100-odd,” says Cash.

But Kim is convinced that longevity is strongly influenced by genetics, and believes that the search will lead to answers. “The amount of data is going up extremely fast and the way we look at the data is improving all the time,” he says. “I’m optimistic that in our lifetime or our children’ lifetime, there are going to be amazing scientific advances that could change how we think about longevity.”

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