Ask the Expert: Jeremy D. Walston, MD, on the importance of understanding frailty and resilience in older people and his 2024 Irving S. Wright Award

A geriatrician expert in basic aging research and as a clinician, Dr. Walson’s work has focused on frailty and resiliency for more than three decades, bolstered by an early career Paul B. Beeson Emerging Leaders Career Development Award in Aging from AFAR in 1998. He is widely recognized for developing the leading tool to assess frailty in older people by measuring weight loss, exhaustion, energy expenditure, grip strength, and walking speed. It has been used in multiple studies of frailty outcomes, aging and frailty related biological underpinnings, and prevention and treatment plans for older adults.

In addition, he is a principal investigator and chair of the Research and Dissemination Core of the National Institute on Aging’s Clin-STAR (Clinician-Scientists Transdisciplinary Aging Research) initiative, which AFAR helps manage.

For his dedication to healthy aging and his numerous contributions to the field of aging research, Dr. Walston received AFAR’s Irving S. Wright Award of Distinction this year. AFAR talked with Dr. Walston to glean insight into his work. His answers were edited for brevity and clarity.

What led you into your career in aging research?

I had lots of grandparents and great grandparents at home when I was a kid. So, by the time I went to medical school at the University of Cincinnati, I was very interested in the health problems of older people. During my internal medicine residency at Hopkins, I just became more and more interested in taking care of older people and the complexity of their aging. I stayed for a geriatrician fellowship that started as mostly clinical research, but also some very basic research into the biology that's changing older people and changing diseases that impact them. That led to my first paper, on type 2 diabetes in older adults, getting published by the New England Journal of Medicine when I was 30. And that’s what led me towards the study of frailty.

In the late 1990s, nobody had yet defined what frailty is; physicians basically just used their clinical gut sense and said somebody was frail if they were in poor condition and going to die relatively quickly. With Linda Fried, then an epidemiologist at Hopkins and now dean of the Columbia University School of Public Health, we set out to discover how to easily measure to create a good definition of frailty — then figure out how older adults become frail. Our team worked carefully with biological and clinical information to better understand how older adults become frail or stay robust or somewhere in between.

How has your work on the frailty exam informed your work measuring resilience?

One of the important things about older people is they don't like to think of themselves as frail. They like to think they're in good shape. And what we've done most recently is see how often that’s actually true, by studying the physical resilience of two groups – 115 knee transplant patients and over 100 individuals after bone marrow transplants. What we wanted to find out is, why do some older people who get new knees stay in a lot of pain, and never really walk well again, while others after a few months are so much better, and feel so much better. What are the major biological differences between them? Knowing those could help decide who should get a knee replaced right away and who needs to wait until some conditions are met. There are a number of inflammatory pathways. Indeed, there could be illnesses without any outward symptoms so patient care teams and patients don't really know about them.

The results of the new study, which we hope to publish in the first half of 2025, say which subsets of people really need to be looked at differently. Oftentimes, physicians don't even know what the important differences are between people that need a knee replacement. Some may benefit right away, but some ought to wait a while and get some other medical issues healed up because they're not going to do well with surgery if they're not well.

One problem with the surgery world is that many doctors don't think twice about whether older people can tolerate surgery. People with AML leukemia and younger than 60 readily get all the treatments, even though they are very difficult for even younger people. But for patients in their 60s or 70s, the decision is too often not even to try surgery or treatment and so these people die of the disease after maybe 18 months. Our study is hoping to describe the biological characteristics of older people who get through some treatments and look pretty good – they’ve pulled the systemic cancer down and can go through this bone marrow transplant and are still going to do great.

You’ve had the unusual opportunity to work with human subjects. How does this build on research with animals?

We've known for a long time that higher levels of chronic inflammatory measures found in the blood were really the most accurate predictor of becoming frail and moving on more quickly to a poor outcome. So, we started looking at the mouse to see if we can get more specific information about biological changes. What we're doing now is going backwards and working with humans and asking, what is it in this subgroup that drives this bad one so much? We're not exactly sure, but it’s probably coming from three or four chemicals and it's often probably systemic in some ways. It changes their muscles quickly, these inflammatory changes driving them down faster than others.

Now we have to figure out what is triggering that. It's not just aging, but probably also things that are tough to detect with standard tests but can be figured out earlier if we're careful.

That’s why I think our physical frailty phenotype has been so helpful for clinicians: They can figure out inflammatory measurements that are going downhill quickly and then try to address them right away. For people in that pre-frail category, you can often pull them out of that big, big barrel. So that's what we work at all the time – making sure people don't get into that too quickly. And if they are, figure out ways to pull them back out.

Tell us more about how your interdisciplinary approach enhances your work and also improves the care of older patients.

We work with a lot of the subspecialties – cardiology, pulmonology, oncology, orthopedics, nursing, even engineering – because they all have seen a subset of patients who don’t tolerate surgery, and they haven’t quite figured out why. Of course, they all want their patients to get through surgery and recover well. By identifying the differences between who’s frail and who’s robust, you can probably still get the frail person to surgery because you’ve been far more careful about what they're like.

And that's been our big message to these subspecialists: All 80-year-olds are not alike. There are those who are doing great and can probably tolerate almost any surgery, and a subset that has frailty or something in between that you have to carefully evaluate before deciding to do a procedure. And then, of course, there are some who are so frail where it’s so likely you’ll damage them or kill them in the operating room that it's best to make their lives as great as possible without surgery.

So, a current focus of your efforts is spreading the word?

If doctors who are not gerontologists know this, they can jump in a little sooner and slow their patients down from that rapid decline.

So that's one important area that we encourage. And all of these subspecialists who a lot of patients end up with, we talk to those doctors and collaborate with them on lots of articles about physical frailty and help them think with their colleagues about how to better take care of this older frail subset. So that's one big piece.

The second big piece of my current research is looking for early indicators of late-in-life frailty. Is there something in the bloodstream by the time people are 50 or 60 that signals they will decline more quickly? Sometimes people do great, and they've had a history of long life in their family and, even if they smoke cigarettes, somehow, they're living to 90. But there's another subset, and we’re trying to figure out how to find them a bit earlier, not wait until they're already so frail we can’t do much to keep them up. We’re looking into inflammatory, metabolic, and mitochondrial factors.

Your award is named for the person who founded AFAR. More than four decades later, what inspires you about where aging research is headed?

It’s inspiring to see how far aging research has come. There are so many great scientists doing clinical and research work to benefit older adults. Those working in aging-related basic science and clinical translation are improving the movement rapidly. What excites me most is the collaborative momentum—bringing together those passionate about caring for older people to translate scientific discoveries into tangible improvements in care. Dr. Wright’s vision to enhance the lives of older adults laid the foundation for much of this progress. His commitment to fostering research that elevates clinical standards remains a guiding influence, and today we’re able to build on his legacy to improve the health of this population.