An illustration of two people biking

Credit: Illustration by Giulia Neri

Why do we all age differently?

Some 80-year-olds seem like they're 60, while some 60-year-olds seem closer to 80. Johns Hopkins researchers are part of a new program to understand and predict the differences in how we all age.

This article was originally published by Dome in its March/April 2023 issue

A new research program at Johns Hopkins is creating tools and frameworks to understand and improve the still-mysterious aging process.

The Human Aging Project, or HAP, brings together experts from the Johns Hopkins University schools of Medicine, Public Health, Nursing, Business, and Engineering to accelerate the development of knowledge and solutions.

Launched in 2021, its goal is to help people stay active and healthy in their later years, says HAP's director, Jeremy Walston, Raymond and Anna Lublin Professor of Geriatric Medicine and Gerontology at the Johns Hopkins School of Medicine.

One day, he says, it might be possible to gather enough genetic, social, and environmental information about individuals to predict their trajectories over their remaining years. Will they be riding bicycles and running for president at 80, or will they be navigating debilitating physical and cognitive declines?

"If you take a room full of 80-year-olds, 15% are frail and vulnerable," Walston says. "Sixty percent have some health problems that are slowing them down. The rest are robust and active."

"What drives some people toward frailty and others toward resiliency?" he asks. "For the group in the middle, the 60% that you can't quite tell, we're trying to tease out how to make those determinations. We need to understand the aging-related biologic changes better in order to improve health trajectories in older adults."

One HAP scholar looking at the many factors that can influence aging is genetic epidemiologist Rasika Mathias.

Mathias, a professor in the Johns Hopkins School of Medicine and the Bloomberg School of Public Health, is using data from whole-genome sequencing to parse out the factors that explain why a person's biological age can be so different from their chronological one.

Her research looks at important measures of biologic age, such as the shortening of telomeres, the protective caps on the ends of chromosomes that protect DNA from deteriorating. Her work is within the Trans-Omics for Precision Medicine, or TOPMed, program, as part of the National Heart, Lung, and Blood Institute's precision medicine initiative.

Those measures, however, are just the beginning, says Mathias, executive chair of TOPMed. "Aging is not just a function of your genes," she says. "A big part is your environment."

"In the past few years, we have seen an increasing number of older adults who live into their 80s and 90s. Our focus is on adding quality to those years, increasing independence. And this is where technologies, new biomarkers, new interventions come in."
Peter Abadir
Associate professor of geriatric medicine and gerontology

Ultimately, she would like to be able to deliver a mid-life "score" to patients, assessing how they are aging and what they could do to prolong healthfulness. She says that remains a long-term goal, though, because it requires combining genetic information with other factors.

"Even if you have all the tools, and that's a big if, we still need the ability to build all these connections," says Mathias, who is pushing for more diversity in the dataset to gain a better understanding of similarities and differences across populations.

By the time a person has lived on this planet for a few decades, the influences on aging seem almost endless. How much stress did that person live with? How was their access to education, health care, or nutritious food? Do they have one or more chronic illnesses?

Looking at Aging from Many Angles

When Mathias thinks of the Human Aging Project, she imagines dozens of people working together to push a boulder up a hill, each person adding perspectives and information.

Social connection, for example, is one factor that seems to influence a person's biological age. Geriatrician Thomas Cudjoe, a HAP researcher, is finding that people with few social connections tend to have higher levels of interleukin-6 and C-reactive protein—biomarkers linked to long-term negative consequences for people as they age, including decreases in cardiovascular and cognitive health.

Cudjoe, a Robert and Jane Meyerhoff Endowed Professor and assistant professor of medicine, says one patient in particular got him thinking about social connections.

It was about five years ago, and Cudjoe, a postdoctoral fellow at the time, was treating an older woman in her Baltimore apartment as part of the Johns Hopkins Home-based Medicine Program.

He saw that she had recurring hospitalizations, and that, "Over time, her connections with people had just disintegrated," he says.

Her outlook and health seemed to improve after Cudjoe introduced her to Johns Hopkins ElderPlus, a Program of All Inclusive Care for the Elderly that offers medical and social care for nursing home-eligible older adults.

HAP researcher Esther Oh, co-director of the Johns Hopkins Memory and Alzheimer's Treatment Center, is using biomarkers to give clinicians tools to predict whether a patient is at risk for delirium after surgery—knowledge that can help both clinicians and patients prepare.

"We used to think of delirium as something you either had or didn't have," explains Oh, associate professor in the School of Medicine's Division of Geriatric Medicine and Gerontology, with joint appointments in the departments of psychiatry and behavioral sciences and pathology. "Now we know that delirium severity and duration are also very important in determining health outcomes after discharge from the hospital. There are a lot of things that we can do to actually reduce the severity of delirium, as well as maybe even shorten its duration."

The Human Aging Project includes the Gerotech Incubator Program, which supports cross-disciplinary teams of trainees from the schools of Medicine, Engineering, Business, and Nursing.

Peter Abadir, the geriatrician who heads the program, says the graduate students, because they are not gerontologists, bring fresh perspectives to identifying problems associated with aging and thinking about how to solve them.

"I want them to observe for themselves and find the problem that interests them and do their problem-solving accordingly," says Abadir, associate professor of geriatric medicine and gerontology.

"When they come up with something they want to work on, we don't tell them how to fix it. Because quite honestly, if we knew how to fix the problem, we would have fixed it by now."

One Gerotech group, for example, has designed a headset that promotes the kind of deep sleep that may protect against Alzheimer's disease and other physical and cognitive decline.

Engineering graduate student Joshua Blair, who has since graduated, was on a team with four other engineering students who surveyed more than 20 clinical sites at Johns Hopkins before settling on the idea of the wearable technology. Called InWave, it uses electroencephalography to monitor brain activity and an artificial intelligence algorithm to time the delivery of specialized sounds that enhance the kind of brain activity needed for deep sleep.

With financial support from HAP and other grants, the group is building 20 prototypes for use in a pilot study, says Blair.

"In the past few years, we have seen an increasing number of older adults who live into their 80s and 90s," says Abadir. "Our focus is on adding quality to those years, increasing independence. And this is where technologies, new biomarkers, new interventions come in."

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Tagged aging