Monday, October 22, 2018

Want to Know When You’re Going to Die?

It's the ultimate unanswerable question we all face: When will I die? If we knew, would we live differently? So far, science has been no more accurate at predicting life span than a $10 fortune teller. But that’s starting to change.

The measures being developed will never get good enough to forecast an exact date or time of death, but insurance companies are already finding them useful, as are hospitals and palliative care teams. “I would love to know when I’m going to die,” says Brian Chen, a researcher who is chief science officer for Life Epigenetics, a company that services the insurance industry. “That would influence how I approach life.”

The work still needs to be made more practical, and companies have to figure out the best uses for the data. Ethicists, meanwhile, worry about how people will cope with knowing the final secret of life. But like it or not, the death predictor is coming.

The clock

Steve Horvath, a UCLA biostatistician who grew up in Frankfurt, Germany, describes himself as “very straight,” while his identical twin brother is gay. So he had a personal interest when, a few years ago, a colleague asked him for help analyzing biological data from the saliva of twins with opposite sexual orientations. The colleague was trying to detect chemical changes that would indicate whether certain genes were turned on or off.

The hypothesis was that these so-called epigenetic changes, which alter the activity of DNA but not the DNA sequence itself, might help explain why two people with identical genes differ in this way. But Horvath found “zero signal” in the epigenetics of the twins’ saliva. Instead, what caught his attention was a powerful link between epigenetic changes and aging. “I was blown away by how strong the signal was,” he says. “I dropped most other projects in my lab and said: ‘This is the future.’”

Horvath became particularly intrigued by how certain chemical changes to cytosine—one of the four DNA bases, or “letters” of the genetic code—make genes more or less active. Given someone’s actual age, looking for these changes in that person’s DNA can tell him whether the person’s body is aging unusually fast or slowly. His team tested this epigenetic clock on 13,000 blood samples collected decades ago, from people whose subsequent date of death was known. The results revealed that the clock can be used to predict mortality.

Because most common diseases—cancer, heart disease, Alzheimer’s—are diseases of aging, the ticking of Horvath’s clock predicts how long someone will live and how much of that life will be free of these diseases (though it doesn’t foretell which ones people will get). “After five years of research, there is nobody who disputes that epigenetics predicts life span,” he says. (...)

Slow the ticking

As we age, the cytosine at hundreds of thousand of spots in our DNA either gains or loses methyl chemical groups (CH3). Horvath’s insight was to measure these increases and decreases in methylation, find the 300 to 500 changes that matter most, and use those to make his clocks. His findings suggest that the speed of the clock is strongly influenced by underlying genes. He estimates that about 40% of the ticking rate is determined by genetic inheritance, and the rest by lifestyle and luck.

Morgan Levine, who completed postdoctoral research in Horvath’s lab and now runs her own lab at Yale, is starting to compare an individual’s epigenetic profile with the profile of cells from the lining of a healthy umbilical cord. The more people deviate from that standard, the worse off they are likely to be. She thinks she will eventually be able to compare various epigenetic age measures to predict even in childhood who is going to be at greatest risk of which diseases—when it’s still early enough to change that future. “Your genes aren’t your fate, but even less so with things like epigenetics,” she says. “There definitely should be things we can do to delay aging if we can just figure out what they are.”

by Karen Weintraub, MIT Review | Read more:
Image:Vera Kratochvil/public domain
[ed. Whether it's epigenetics, bionics, gene editing or transhumanist brain uploads, immortal life is coming. We just need to survive politicians, climate change, bio-terrorism and nuclear war first. See also: Actors are digitally preserving themselves to continue their careers beyond the grave.]