The key to a long life has little to do with "good genes"

In 2013, Google Co-founder and CEO Larry Page has announced the formation of a new Alphabet entity dedicated to solving the pesky puzzle of mortality. Since then, the $ 1 billion longevity laboratory known as Calico – named California Life Company – is trying to unravel the fundamental biology of aging in the hope of eventually defeating death. The hyper-secret research company has published few details about what it's actually doing in its Silicon Valley lab, but there have been hints. Cynthia Kenyon, a renowned geneticist, was one of the company's first recruits. She is 20 years old, she has doubled the life of a laboratory worm by returning a single letter in her DNA.

Shortly after arriving at Calico, Kenyon recruited a postdoc in UCSF bioinformatics, Graham Ruby. He did not want to be interested in the genetics of worms or study the colony of naked and perennial mole rats in society. He wanted to first ask a much broader question: what role do genes play, anyway, in determining a person 's lifespan? Other scientists had already tried to ask this question, with conflicting results. To clarify, it would require a lot more data. Calico has joined the largest family history database in the world: the consumer genetics and genealogy firm, Ancestry.

In 2015, the companies signed a research partnership to study the human inheritance of the life span. Ruby was at the head of the complaint to review the vast family tree forest of Ancestry. By analyzing the genealogies of more than 400 million people who have lived and died in Europe and the United States since 1800, he found that while longevity tends to reign in families, your DNA has much less influence that you do not think about the duration of your life. The results, published Tuesday in the newspaper Genetic, is the first study to be made public by the collaboration, which ended quietly in July and whose terms remain confidential.

"The true heritability of human longevity for this cohort should not exceed 7%," says Ruby. Previous estimates of the amount of genes explaining life span variations ranged from about 15 to 30%. So what did Ruby discover that previous studies had missed? How often do human lovers go against the old adage that "opposites attract".

It turns out that, in each generation, people are much more likely to choose partners with a lifespan similar to what chance might predict. The phenomenon, called "assortment assortment", could be based on genetics or socio-cultural traits, or both. For example, you can choose a partner who also has curly hair, and if the curly line ended up being associated with a long life, this would inflate the heritability estimates of the life span passed on to your children . Same for non-genetic features such as wealth, education and access to good health care. People tend to choose partners in the same income bracket with the same terminal diploma, both of which are associated with a longer and healthier life.

The first clue that something other than genetics or a shared home environment might well be at work came when Ruby tried to watch in-laws' parents. His analysis began with a set of family trees including 400 million individuals. The data had been cleaned, unidentified and assembled by genealogists and computer scientists at Ancestry based on public information generated by subscribers. Using the basic laws of heredity – each inherits half of its DNA from one parent and the other from the other, repeated over generations – Ruby's team examined the relationship of two people and their life span. They investigated parent-child couples, sibling couples, various cousins, and so on. Nothing very surprising happened there.

But when Ruby examined the in-laws, things started to get strange. The logic suggests that you should not share large pieces of DNA with your brother's or sister's spouse, such as your brother's wife or your sister's husband. But in Ruby's analysis, people linked by the marriage of a close relative were almost as likely to have the same lifespan as people linked by blood. "I get hurt a little bit by being surprised by that," Ruby said. "Even though no one has previously demonstrated the impact of assortment matching, it fits well with the way we know that human societies are structured."

The research could affect the entire field of longevity studies. Ruby says that this does not invalidate previous work on identifying individual genes involved in aging or age-related diseases, but he suggests that finding more of these genes will be much harder to come by. To find them, scientists will need huge cohorts to achieve sufficient statistical power. This should not be a problem for Calico who, in addition to the family trees, also had access to anonymized DNA information from millions of genotyped Ancestry clients as part of the research partnership.

The companies have at least one other article on the genetics of longevity that is currently under review by peers. A spokesperson for Ancestry said that, in accordance with the original terms of the agreement, the partnership between Calico and Calico is concluded by the presentation of the research covering these results. Calico is free to follow any leads from the analysis, but the company says nothing about what they might be for the moment. (A spokesman for Calico declined to comment on Ancestry's collaboration beyond the results of today's release.)

For the moment, the big advantage seems to be that humans have more control over the length of their lives than their genes. It's all the other things that families share – houses and neighborhoods, culture and cooking, access to education and health care – that make a much bigger difference in the overall numbers that might one day honor your falls.

Perhaps that's why Catherine Ball, Annestry's chief scientist, said the company was not planning to offer a longevity score for its DNA test products in the near future. "At the moment, a healthy life seems to be more dependent on the choices we make," she says. It shows places in the data where the life span has been very successful – for men during the First World War, then in two waves in the second half of the twentieth century, while men, then women, took the habit of smoking.

"Do not smoke and do not go to war. These are my two tips, "she says. And maybe take the time to do some exercise. Ball already has a Tuesday morning pencil workout in her schedule. This time, she says, she will not cancel it at the last minute.

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