FANCY living for a century? Your luck may be in if you carry protective variants of four newly discovered genes. One gene determines blood group, another helps regulate cellular life cycles, while the third is involved in how the immune system recognises the body’s own cells. The fourth has been shown to extend lifespan in fruit flies.
Uncovered by searching the genomes of centenarians, the genes join APOE, which is known to influence Alzheimer’s risk, as the bits of our genome most clearly associated with lifespan. They are tantalising clues to uncovering the mystery of why we age, and could help us prevent age-related diseases.
Studies of identical twins suggest that genetic make-up plays a big part in longevity. It is common for siblings 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 Stuart Kim at Stanford University in Calfornia, whose team carried out the latest research.
But which genes are responsible? Several studies have looked for variations that are more or less common in long-lived people, but until now, only APOE turned up consistently.
For example, in 2014, Kim published a study comparing the genomes of 17 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 these supercentenarians might share a rare gene variant that would explain their tenacity but nothing turned up, and the media announced the death of the “longevity gene”.
This time Kim 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 indicate 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 seems to 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 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 how long someone will live 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. “I’m optimistic that in our lifetime or our children’s lifetime, there are going to be amazing scientific advances that could change how we think about longevity.”
(Image: Juan Carlos Ulate/Reuters)
This article appeared in print under the headline “Genes that help you live to 100”