October 5, 2015

Read this if you want to have the time of your life


Steve Horvath, a geneticist and biostatistician at UCLA, has developed a cellular biological clock that has impressed researchers with its accuracy, how easy it is to read and the fact that it ticks at the same rate in many parts of the body — with some intriguing exceptions that might provide clues to the nature of ageing and its maladies.

Horvath's clock emerges from epigenetics, the study of chemical and structural modifications made to the genome that do not alter the DNA sequence but that are passed along as cells divide and can influence how genes are expressed. As cells age, the pattern of epigenetic alterations shifts, and some of the changes seem to mark time. To determine a person's age, Horvath explores data for hundreds of far-flung positions on DNA from a sample of cells and notes how often those positions are methylated.

“I wanted to develop a method that would work in many or most tissues. It was a very risky project,” Horvath says. But now the gamble seems to be paying off. By the time his findings were finally published last year1, the clock's median error was 3.6 years, meaning that it could guess the age of half the donors to within 43 months for a broad selection of tissues. That accuracy improves to 2.7 years for saliva alone, 1.9 years for certain types of white blood cell and 1.5 years for the brain cortex. The clock shows stem cells removed from embryos to be extremely young and the brains of centenarians to be about 100.

The reviews came back in the spring: more disbelief, and another rejection. Horvath didn't blame the reviewers for being sceptical. “Everyone who develops biomarkers knows what to expect: a very strong biomarker gives you a correlation of, say, 0.6 or 0.7.” For example, the correlation between age and the length of telomeres is less than 0.5. For Horvath's clock algorithm, that figure is 0.96. He confesses that he had trouble believing it himself until other researchers independently confirmed the tight association.

“Such tight correlations suggest there is something seemingly immutable going on in cells,” says Elizabeth Blackburn of the University of California, San Francisco, who won a Nobel prize for her research on telomeres — caps on the ends of chromosomes that shorten with age. It could be a clue to undiscovered biology, she suggests. And there may be medical implications in cases in which epigenetic estimates do not match a person's birth certificate.


Picture; Compact Object (1962) by Natsuyuki Nakanishi
A plastic egg with bones, watch and clock parts, hair, eggshells, lens bits, ...

Times as artificial constructs born form synthetics. A plastic egg giving birth to both flesh and time, to the real, the material, and the ephemeral and elusive. Can one exist without the other? Is time internalized mechanically by the flesh, or is it the other way around? Time made flesh... by the machine? Our time isn't really all that similar to physical or even biological time. Ours ticks at different rates from day to day, from cradle to the grave. From atomic vibrations measuring millions of intervals in a single second, to the number of pressure waves transmitted by your local church bell, not all times are made equal. Then again, pulsars are very good clocks but they do not tell time the way Chicxulub did when it reshaped Mexico's Yucatan peninsula.

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