Longevity is one of the hottest areas of science, but there's a curious hole in the research: Scientifically speaking, nobody knows how to measure aging, much less predict reliably how people will respond to time's ravages.

After all, aging isn't just chronological. Some people are spry and nimble in their elder years. Others are afflicted by the diseases of aging — heart disease, diabetes, cancer, Parkinson's, Alzheimer's, dementia and stroke — by middle age.

Many researchers think those diseases are manifestations of a common underlying cause, known conversationally as aging but as yet undefined by science. They call for studies that would gather exhaustive clinical and genetic data from thousands of people over many years, hopefully identifying the biological mechanisms of growing both older and unhealthier.

"Unlike models of drug development for the diseases of aging, which have consensus endpoints to evaluate, we have not reached a consensus in aging," said gerontologist Don Ingram of the Pennington Biomedical Reseach Center. "We don't know how to predict how someone will function later in life, and we need to."

That such a basic gap exists seems counterintuitive. After all, longevity-enhancing research has never been so prominent. Following leads revealed by animals on calorically restricted diets — they tend to live longer, apparently because dietary stress triggers cell-protecting routines that prevent aging diseases — scientists have found genes and pathways that can be targeted by drugs.

Resveratrol, a natural compound that affects mitochondrial function and DNA repair, and its pharmaceutical derivatives have been used to prevent diabetes in obese mice. Now they're being tested in humans. Manipulations of the growth-regulating IGF-1 pathway have extended lifespans in lab animals. Rapamycin, used to suppress autoimmune responses in people receiving organ transplants, has extended the lives of elderly mice. It's now being tested in mice against specific diseases.

All these findings hint at a universal aging process, and the concept has finally gone mainstream. Longevity research earned a December U.S. News and World Report cover story, and a Time cover package this month. But these experimental results are preliminary, and only tweak pieces of a larger puzzle. Gerontologists say that to develop drugs that slow the aging process, they need to know far more about aging's biology.

"We need to have a set of thousands of people, representing all groups, that are closely followed on health measures. They'd be tested three or four times a year, for five or 10 years. Then you'd have a good sense of the trajectory of aging," said David Harrison, a Jackson Laboratory gerontologist who co-authored the landmark paper on rapamycin's life-extending potential.

According to Harrison, people enrolled in the proposed study could, after several years, opt to take rapamycin. That would let researchers see whether it works in people as it does in mice. If so, they'd also have a detailed account of resulting gene and protein changes, and insight into whether rapamycin works better in some people than others.

Rapamycin does have toxic side effects. Though treatment could be stopped immediately, safety couldn't be guaranteed. But as Harrison noted, "There are hundreds of clinics for rich people to take anti-aging treatments that are at best placebos, and they pay ungodly amounts of money. Wouldn't some people, at least, like to participate in a science-based study where they have their trajectory of aging measured and monitored?"

For now, such a study wouldn't be run by the Jackson Laboratory or a governmental funding agency, like the National Institutes of Health. It would likely take place under the auspices of a private foundation, with study participants footing much of the bill.

But take rapamycin out of the equation, and a long-term study of aging biomarkers would be suitable for institutional funding. Of course, it would still be expensive. But even a long-term study of aging in rodents would be useful, and it would also be more affordable, said Felipe Sierra, director of the National Institute on Aging's Division of Aging Biology.

"If we had a set of biomarkers that at 12 months of age predicted which mice would die younger or older, then we could shorten mouse studies to 12 months," said Sierra.

To get funding, such a study would have to overcome the mixed legacy of a decade-long project launched by the NIA in the late 1980s. Researchers looked for biological markers in rodents, but had neither the technology nor the understanding necessary to find them.

"We spent a lot of money and got nothing. Now it's taboo in our field," said Sierra. "But we weren't ready. Each one of us was looking for a single biomarker of aging. It turns out that there's no such thing. But with the advent of modern metabolomics and proteomics, it might be possible to do this."

Sierra noted that — at a moment of cheap gene sequencing and high-powered genome association studies, when desktop computers crunch terabytes of gene and protein data — the most reliable indicator of aging is still whether people look old. It's hardly scientific.

"The technology has advanced to the point where we should be able to try," said Sierra.

Image:Lynn Lin/Flickr

See Also:

Brandon Keim's Twitter stream and reportorial outtakes; Wired Science on Twitter. Brandon is currently working on a book about ecological tipping points.