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Discovering the Biological Roots of Frailty

By Jim Duffy

Most people can recognize frailty: It's somewhere in the mix of advanced age, stooped shoulders, wobbly gait, iffy grip and shrinking body mass.

But where, exactly? Biostatistician Karen Bandeen-Roche is seeking to translate frailty into precise diagnostics by studying participants in the Women's Health and Aging Study (WHAS).

Actually a progression of linked studies dating back to the early 1990s, WHAS is tracking the progress of women as they age in an effort to determine predictors of the changes in physical functioning that lead many older adults to experience difficulties completing everyday tasks. Frailty is more than just a matter of weakness and low energy levels, however; it's also strongly associated with falls, hospitalizations, disability and death.

One hypothesis Bandeen-Roche, PhD, is testing posits that frailty is a full-blown syndrome rather than a mix-and-match collection of symptoms. For a study published last year in the Journal of Gerontology, she tried to employ a combination of five measures to distinguish the frail from the non-frail: weakness in a hand-grip test, observed walking speed, amount of reported physical activity, level of reported exhaustion and weight loss over time.

If frailty is a syndrome, those measures should aggregate quite clearly into two main groups: the frail and the non-frail. In fact, that's just what happened with the numbers.

Now Bandeen-Roche is trying to understand the biological roots of the proposed syndrome. Working through the Johns Hopkins Older Americans Independence Center, she's looking for biomarkers that may help predict who is most at risk of becoming frail. Interventions designed to delay or even prevent the onset of frailty could then be targeted more efficiently and more effectively.

She is also part of a new working group of researchers from various disciplines who are sharing ideas about how to delve into the biological underpinnings of frailty. Bandeen-Roche was originally trained as an engineer, and she still sounds like one when describing where this work might lead.

"If you have water behind a dam, there are forces at work that may become so great that the dam breaks," she says. "Whatever those forces are—rainfall, erosion, or what have you—we can describe them in engineering through a system of equations. We can make some predictions and prepare for things. We want to do the same thing with respect to frailty."

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