Are We Getting Closer to a Biological Time Clock?

Two of the principal theories of aging focus on wear-and-tear and a biological time clock. Of course, these may be complementary. Each cell may have a certain number of "ticks" built into, but the timing could be altered by wear-and-tear. Two recent articles got me thinking about this. First, in last week's Economist there was a review of a book on birds by field biologist Noah Strycker, titled "The Thing With Feathers: The Surprising Lives of Birds and What They Reveal About Being Human". Here is what really struck me:

PLATO suggested that humans were “bipeds without feathers”. People walk on two legs like most avian species. They are also largely diurnal and rely upon sight as their primary sense. All of this, incidentally, is unlike most mammals. Yet how much do humans really share with birds?..It turns out that humans and hummingbirds, despite differences of scale and style, enjoy a lifespan of about a billion heartbeats, a rule that holds good for many warm-blooded animals, from mice to elephants.

So, here is tacit acceptance of the biological time-clock theory with the added information that this may transcend species.

Then came an article in Nature today chronicling a fascinating research program by Steve Horvath at UCLA, in which he can tell with remarkable accuracy how old a person is by examining various cell samples.

He has discovered an algorithm, based on the methylation status of a set of these genomic positions, that provides a remarkably accurate age estimate — not of the cells, but of the person the cells inhabit. White blood cells, for example, which may be just a few days or weeks old, will carry the signature of the 50-year-old donor they came from, plus or minus a few years. The same is true for DNA extracted from a cheek swab, the brain, the colon and numerous other organs. This sets the method apart from tests that rely on biomarkers of age that work in only one or two tissues, including the gold-standard dating procedure, aspartic acid racemization, which analyses proteins that are locked away for a lifetime in tooth or bone.

Both Ideker [at UCSD] and Horvath expect that the most interesting use of the clock will be to detect 'age acceleration': discrepancies between a person's epigenetic and chronological ages, either overall or in one particular part of their body.

Such discrepancies could be signs that something is awry. In work due to be presented at the November meeting of the Gerontological Society of America, Brian Chen of the US National Heart, Lung, and Blood Institute (NHLBI) in Framingham, Massachusetts, teamed up with Horvath and others to analyse methylation data collected on more than 2,100 men and women aged 40 to 92 as part of the Framingham Heart Study. The researchers concluded that for every five-year increase in age acceleration, the risk of dying from any cause during the study jumped by 15%. Horvath says that unpublished work from two other large studies also finds epigenetic age acceleration to be a substantial risk factor for mortality, even after controlling for chronological age and other well-known risk factors.

The story of how this research came about and what it might mean seems like prime material for a movie, but in particular it seems that we may be inching closer to an improved biological theory of aging.