Diagnostics & Imaging Week National Editor

Theranostics is the emerging science of determining a person's susceptibility disease and then providing preventive therapies.

The ultimate theranostic? Perhaps the ability to predict early aging and thus help to develop anti-aging strategies and therapies.

Doing exactly this is a possibility foreseen in new research from the Buck Institute for Age Research (Novato, California). This research, on a "lower" form of life, offers a pathway for predicting which human may be long-lived, which susceptible to early aging.

But how accurately and what then ... given the possibility of a whole range of unpredictable, and unintended, consequences?

Led by Simon Melov, PhD, a Buck faculty member and lead author, the study involved the advanced genetic analysis of nematode worms (C. elegans), to predict their longevity, with Melov telling Diagnostics & Imaging Week that the work offers "proof of principle" that could ultimately provide the same information concerning human beings.

"Physiological age," he noted, "is independent of and may be different than chronological age that's something that we've had a good deal of difficulty getting a handle on, [lacking] predictive and robust methods."

The research identified biochemical features, used as biomarkers, that were employed in predicting which of the nematodes would live the longest, which would die off early, or earlier.

Nematode worms, the researchers say, are similar to humans in that some show premature aging and die much earlier than others, while these others remain "spry" and live longer ("spry," we can't help noting, being the demeaning term frequently used to describe an active elderly human being).

Utilizing whole-genome expression profiles of individual wild-type worms covering the entire nematode lifespan, the researchers were able to predict the aging of the worms. This was then correlated with age-related behavior and survival.

The conclusion of the study: that this offers "the first step toward identifying similar biomarkers in humans," according to the researchers.

The analysis was done by means of a fairly standard approach in current genetic analysis, Melov said, the use of microarrays. But he said that many more were used 104 in all than ever before for this type of predictive work.

"A lot of studies have been done looking at aging with microarrays in multiple different species, everything from mice to human beings," Melov said. "However, those studies weren't nearly meeting the rigor of our studies or such a uniform set of samples."

He added that he was sure "the numbers [of microarrays] will be continually going up and improving" in future studies.

This will be necessary and a likely next step in the research because the prediction of nematode lifespan was far from perfect.

"[W]e were able to predict the ages of the animals 70% of the time, which is far better than anything that has been done before," he said. But he readily acknowledged that this percentage would have to be much higher, 90% and higher, to be useful in humans.

The first step in human use might be in looking at individual tissues to determine their physiological age, he suggested, not for predicting an individual human's tenure on the planet.

The technique might help to determine, for instance, if a person's "muscles are performing better than expected, or function worse than their chronological age," and so be able to tell a person, "You're not in very good shape. You should do something about it."

As to determining whether you will live long, or die relative young, he said, "I'm not certain you could actually predict mortality" using this method. But it might help to identify if your physiological aging is moving faster than your chronological aging."

Another more important and relevant goal, he said, might be to use the biomarkers of aging to develop anti-aging therapeutics, through provision of a baseline for clinical trials of anti-aging medicines, otherwise impossible given the relatively lengthy lifetime of humans.

"Currently, we don't have the therapeutics which are effective against aging per se, nothing which really works in human beings," Melov told D&IW, "we only have interventions. We'd like to have some kind of a treatment, along with this prediction, which will improve function. And then you would take a second test, showing whether you have benefitted from this therapeutic.

"This is the first evidence that physiological age can be predicted non-subjectively," said Melov. "This is a first step."

The research appears in the Nov. 20 online edition of Aging Cell.

Melov plans to use this biomarker technology in studies involving humans who undertake various forms of exercise over a set period of time.

He published a study in 2007 showing that regular strength training reversed aspects of aging in skeletal muscle in healthy seniors.

Future steps will include a larger study involving wild-type nematodes to see if the same suite of genes remains active in the aging process and to see if the predictive rate can be increased. And mouse studies may focus on gene expression profiling in different types of body tissue for example, does heart muscle age faster than liver tissue given a certain set of environmental or nutritional factors?

Melov said, "I am confident that at some point there will be a non-subjective method of determining how old someone is with a high level of confidence."

The Buck Institute says it is the only freestanding institute in the U.S. devoted solely to basic research on aging and age-associated disease.