Columbia’s Linda P. Fried: Robust Research on Frailty
Scientist Interview: January 2011
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Assuming this hypothesis is true, where do you go with it? How does it change clinical practice and perhaps research agendas as well?
One question that we’re investigating, along with many other people, is this: if so many systems are dysregulated, is there something that’s kicking all of them off? Is there either an underlying biologic shift that drives all these different systems in parallel or in a cascade? I hypothesized originally that the vicious cycle of frailty was a manifestation of energy dysregulation.
We have asked in that regard, for example, if, for example, mitochondrial function—energy production in the cell—is playing a role in this. This might explain why so many systems are getting dysregulated simultaneously. On the other hand, this syndrome of frailty also seems to be associated with certain catabolic diseases, like HIV, congestive heart failure, and chronic obstructive pulmonary disease. This would suggest that this syndrome of frailty might be a final pathway that can be kicked off by some disparate processes.
So how do you approach it to prevent or at least postpone frailty? Do you see a day when someone takes a drug to prevent frailty from developing, or is that far too simplistic?
Obviously there are lots of drug companies very interested in this. If we could find the lever that kicks this off, that would be a big deal. Another clinical implication is that if people already have early frailty, as our early papers showed, they’re at a very high risk of becoming frail. So this is a point at which we want to intervene. Should we be doing clinical screening for people at risk of severe frailty? And if we want to intervene, what do we intervene on? The biology suggests this is a multi-systems problem, so just intervening on any one thing is probably unlikely to yield any meaningful effect.
If this latter is the case, then we have an interesting model, and that’s physical activity. If you look at the literature on the biological and physiological effects of physical activity—of the impact of physical activity on health—you’ll see one group of papers says that physical activity increases strength, another group says it increases muscle mass, another says physically fit people extract oxygen better and actually function better.
Yet another set of papers will show that exercise lowers blood pressure and that it’s a good intervention for hypertension. Physical activity, of course, improves insulin sensitivity and glucose tolerance; it keeps weight down and may actually modulate inflammation and some hormonal functions. There’s some evidence that physical activity up-regulates mitochondrial function. So if you wanted to choose one intervention that might tune many systems involved in frailty—at least for a proof of principle—you might look at physical activity for a model.
And does it work with frailty?
"From the (Science Watch, July/August 2010)
feature: "Where Everything Old is News."
An elderly couple sit on a bench next crocus flowers
in a park in Duesseldorf March 17, 2010. REUTERS/Ina
Fassbender
There’s informative data from Maria Fiatarone Singh, of the University of Sydney, and her colleagues. They published a landmark trial in JAMA showing that nursing-home patients she defined as fail actually improved strength and walking speed with an exercise intervention, and that they could still respond even though they were so old and frail. Indeed, they responded dramatically. If that’s the case, it might be that at least in the early stages of frailty a physical-activity intervention might be successful and it might be an ideal intervention for greatest effect, because it affects so many different parameters of the organism.
We’re also investigating the idea, from clinical observations, that if older people are engaged in contributing to society, to make a difference, it helps them stay more physically, cognitively, and socially active—and that would be a key preventative intervention.
That certainly seems reasonable, but is it something that can be tested with a clinical trial?
In the early 1990s, I designed a model for testing that—with Marc Friedman, president of an organization called Civic Ventures—and this model is now a program called Experience Corps in 22 U.S. cities. It’s an evidence-based senior volunteer program, high intensity, 15 hours a week, in which older adults volunteer in public elementary schools to improve the success of children. Hidden in there simultaneously, however, is a design for health promotion for these older adults, by increasing their physical activity, cognitive activity, and social activities while giving them meaningful roles in society.
We’re now three years into a randomized-controlled trial in Baltimore to evaluate the impact on health and well-being of older adults, and at the same time to demonstrate that the social capital of older adults in our aging society could make a profound beneficial difference for our kids. We randomized older adults to either Experience Corps or to a control, which is a referral to a standard current volunteer opportunity in the community and the opportunity in two years to go into Experience Corps. So, on the clinical side, we hope to be able to tell in a couple of years whether by keeping these older adults active in this way—physically, cognitively, and socially—we can prevent frailty and disability.
Do you have any preliminary data suggesting that it works?
We do. My colleague Erwin Tan published two papers showing that older adults who go into Experience Corps and who were not previously physically active increased their physical activity at a rate equal to that of older people in exercise trials. So they’re getting an increase in the dose of prevention.
My colleague Michelle Carlson published the evidence just in the last year that black women with just a high school education who work in Experience Corps show an increase in brain activity on an fMRI. She published a really elegant paper showing breathtaking changes in brain activity in executive-function areas of the brain, and these are people in Experience Corps who started out with low education and being at risk for dementia. She had previously published a paper showing dramatic improvements in executive function in older people with low-to-normal cognitive abilities.
Can you give us a prediction for the near future on your research on frailty and the lessons from Experience Corps?
The science is hopefully going to roll out at all levels. And the potential is for interventions like Experience Corps to create win-wins from our aging society and while bringing prevention of frailty into communities and improving wellbeing for multiple generations through one vehicle.
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Photo: Manuello Paganelli.