Biology of Frailty
The first of its kind in the country, a new program at Hopkins Bayview tries to improve the quality of life for older adults.

Co-director Jeremy Walston (left) and Neal Fedarko: “If you understand the basic biology, the basic pathways, that give rise to frailty,” says Fedarko, “then looking at other diseases is going to be very similar.”

Growing old is inevitable. Becoming frail as you age is not. Samuel Durso, acting director of the Division of Geriatric Medicine and Gerontology, has a photo of a spry, brightly smiling elderly woman in his Hopkins Bayview office that reminds him of that fact.
Willie Mae Mitchell was 93 and living independently in late 2005 when she went to the Johns Hopkins geriatrics and gerontology clinic at Keswick, a long-term care facility in Northwest Baltimore. She wanted a physician’s note clearing her to take a class—in line dancing.

Although Mitchell’s muscle mass had declined and she was walking more slowly—telltale signs of frailty—she didn’t have the fatigue often associated with it. “She was at an early stage. We were thrilled that she was going to be celebrating her birthday with family back in Los Angeles,” Durso recalls.

Within a year, however, Mitchell became ill, declined rapidly over a short period of time and died. Because of her frailty, she was vulnerable to something others her age or younger might have overcome.

Frailty—characterized by weight loss, muscle weakness, exhaustion and other symptoms—is a distinct medical syndrome with molecular and genetic causes that might be prevented or alleviated, according to research by Hopkins’ geriatrics and gerontology division.

To understand the biological mechanisms that underlie frailty and develop treatments for them, the division recently launched a new Biology of Frailty Program—the first of its kind in the country. The program’s researchers will focus exclusively on uncovering the biochemical, physiological, immunological and other factors that cause some 7 percent to 10 percent of older people to become frail. For a far larger percentage of elderly people, frailty is a complicating factor in other conditions, such as heart disease.

The researchers hope to translate their findings into clinical treatments to improve the quality of life for these older adults, a group projected to be 20 percent of the population by 2020.

“This is such an important program and initiative,” says Durso. “This clinical syndrome is at the heart of geriatric medicine.” 

For the past decade, Jeremy Walston, co-director of the new program, has conducted groundbreaking research on frailty. His 1998 study included clinical measurements—such as grip strength, walking speed and weight loss—that could be used to define the frailty “phenotype,” or group of characteristics. That definition remains essential to diagnosing the syndrome and addressing its causes.

Frail patients are more susceptible to graver consequences of illness. “If they catch a cold during flu season or fall and break their hip, everything just starts going downhill, versus somebody who is the same age but not frail who would convalesce for awhile and get better,” explains Neal Fedarko, a Ph.D., the program’s other co-director, who is a specialist in the biochemistry of cancer, which may be similar to that of frailty.

The multidisciplinary group’s next step is to delve more deeply into the syndrome’s roots. They will explore declines in the immune systems of the elderly, study the impact of chronic inflammation, investigate the role of chronic viral infections on frailty and develop novel interventions that target specific physiological systems. The group also wants to convince physicians to use clinical measurements to routinely screen elderly patients for frailty.

Fedarko is enthusiastic about the program because the factors that underlie frailty may have ties to other illnesses, such as heart disease or cancer.

Looking at Willie Mae Mitchell’s photo, Samuel Durso says, “She’s the kind of person we’re trying to help. She was delightful. If we could have kept her going to 120, that would have been great.”

—Neil A. Grauer