The Key to a Long Life Has Little to Do With Good Genes

July 1st, 2020 3:48 am

In 2013, Google cofounder and CEO Larry Page announced the formation of a new Alphabet entity dedicated to solving the pesky puzzle of mortality. Since then, the billion-dollar longevity lab known as Calicoshort for California Life Companyhas been trying to tease apart the fundamental biology of aging in the hopes of one day defeating death. The hyper-secretive research venture has released few details about what it actually does inside its Silicon Valley lab, but there have been hints. One of the companys first hires was renowned geneticist Cynthia Kenyon, a UC San Francisco researcher who 20 years ago doubled the lifespan of a lab roundworm by flipping a single letter in its DNA.

Shortly after joining Calico, Kenyon recruited a UCSF bioinformatics postdoc named Graham Ruby. He didnt want to dig into worm genetics or study the companys colony of long-lived naked mole rats. He wanted to first ask a much broader question: how big a role do genes play, anyway, in determining how long someone lives? Other scientists had tried to ask that question before, with conflicting results. To clear things up would require getting much, much more data. So Calico went to the biggest family history database in the world: the consumer genetics and genealogy firm Ancestry.

In 2015, the companies inked a research partnership to investigate the human heredity of lifespan, with Ruby leading the charge to sift through Ancestrys vast forest of family trees. What he found by analyzing the pedigrees of more than 400 million people who lived and died in Europe and America going back to 1800 was that although longevity tends to run in families, your DNA has far less influence on how long you live than previously thought. The results, published Tuesday in the journal Genetics, is the first research to be made public from the collaboration, which ended quietly in July and whose terms remain confidential.

The true heritability of human longevity for that cohort is likely no more than seven percent, says Ruby. Previous estimates for how much genes explain variations in lifespan have ranged from around 15 to 30 percent. So what did Ruby uncover that previous studies had missed? Just how often amorous humans go against the old adage that opposites attract.

It turns out that through every generation, people are much more likely to select mates with similar lifespans than random chance would predict. The phenomenon, called assortative mating, could be based on genetics, or sociocultural traits, or both. For example, you might choose a partner who also has curly hair, and if the curly-haired trait winds up being somehow associated with long lifespans, this would inflate estimates of lifespan heritability passed on to your kids. Same thing for non-genetic traits like wealth, education, and access to good health care. People tend to choose partners in their same income bracket with the same terminal degree, both of which are associated with living longer, healthier lives.

The first hint that something other than genetics or a shared family environment might be at work came when Ruby tried looking at in-law relatives. His analysis started with a set of family trees comprising 400 million individuals. The data had been cleaned, de-identified, and stitched together by genealogists and computer scientists at Ancestry based on subscriber-generated public information. Using the basic laws of heredityeveryone inherits half their DNA from one parent and half from the other, repeated across generationsRubys team looked at how related two people were and how long they lived. They investigated parent-child pairs, sibling pairs, various cousins, and so on. Nothing much surprising popped out there.

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The Key to a Long Life Has Little to Do With Good Genes

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