9. Toward Living Better, for Longer

9. Toward Living Better, for Longer

With the aging of the baby boomer generation and ever-increasing life expectancy, our nation faces a “silver tsunami”: the number of Americans ages 65 and older is projected to nearly double between 2018 and 2060 — from 52 million to 95 million, according to the U.S. Population Reference Bureau. That means the number of people with conditions associated with old age — notably dementia, heart disease, osteoarthritis and diabetes — will skyrocket unless something changes.

Enter the CIM-supported Johns Hopkins Human Aging Project (HAP), led by geriatrician and gerontologist Jeremy Walston, the Salisbury Family Foundation CIM/HAP Scholar. The bold undertaking, launched in 2021 and based at Johns Hopkins Bayview Medical Campus, is ambitious in its scope: The HAP is assembling the very best minds at Johns Hopkins to slow aging’s impact and improve life for the nation’s rapidly aging population.

“In just four short years, the Human Aging Project has become a national leader in translating scientific advances into clinical breakthroughs that will dramatically improve the lives of older adults, allowing them to live independently for longer and with a better quality of life,” says Walston, the Raymond and Anna Lublin Professor of Geriatric Medicine.

Already, the Human Aging Project has attracted more than $60 million in funding, and 13 faculty members are now supported in aging research as HAP Scholars. Eleven of those HAP Scholars have been funded through CIM, Walston notes.

One component critical to the mission of HAP is the important role played by biomedical engineers at Johns Hopkins — work fueled by recent dramatic advances in computer networking capabilities, innovations in artificial intelligence, and “our ability to produce and handle data and do computation at unimaginable scales,” says Ed Schlesinger, dean of Hopkins’ Whiting School of Engineering, an important HAP partner. “All of these tools allow us to address complex problems, such as the infirmities of old age, that until just recently we considered intractable,” Schlesinger says.

Walston, whose own research focuses on the biology of frailty, says that early funding — and vision — provided by CIM has been key to HAP “building a bigger tent” for aging research and clinical advances.

“CIM has allowed us to dramatically expand the field of aging research at Johns Hopkins by bringing together faculty members who may not have been focused on aging — in fields like engineering, oncology, neurology, even business — and having them work directly with those providing patient care to older adults, such as nurses and geriatricians, who have identified problems that need to be solved,” says Walston.

He adds, “We’re building bridges in a way that can rapidly accelerate treatment advances for older adults.”

Leveraging Technology

Some of those important breakthroughs will no doubt unfold in an expansive new HAP hub for collaborative research, housed on the Bayview Medical Campus in space that was formerly a cavernous gymnasium.

The 10,000-square-foot center marks the first time that engineering students and faculty members from Johns Hopkins’ Homewood campus will have a dedicated research home for collaboration with clinicians and researchers at Johns Hopkins Bayview, a campus with a rich array of geriatrics-related clinics, centers and labs.

“The new space offers an exciting opportunity for our engineers to work together with clinicians, nurses, older adults and their caregivers to come up with technology-driven solutions to some of the biggest challenges older people face, such as social isolation or mobility issues,” says Najim Dehak, an associate professor of electrical and computer engineering and the 2021 Whiting School of Engineering/HAP Scholar. “We aim to leverage technology to extend the time that older adults can remain living safely and independently at home.”

With its plentiful conference rooms, labs and offices, the space will provide a new home for engineers affiliated with the Johns Hopkins Artificial Intelligence & Technology Collaboratory for Aging Research (AITC) — which was established in November 2021 with $20 million in funding from the National Institute on Aging — and for multidisciplinary teams working within the Gerotech Incubator Program.

The Gerotech teams bring together engineering students with nursing doctoral students, medical residents, business students and faculty mentors to tackle an aging challenge, develop a prototype solution and — in some cases — move the product through to commercialization.

The centerpiece of the new space, which is slated to open in late 2024, is a model apartment. It is equipped with many of the features of an actual home. “It will be here that we can bring older adults and their caregivers to conduct clinical tests of devices that have been developed through the AITC and by Gerotech teams,” says Dehak, who co-directs the Gerotech Incubator Program together with gerontologist Peter Abadir, the Salisbury Family Foundation CIM/HAP Scholar.

Technological solutions for healthier aging will run the gamut, Dehak says, from robotic social companions to sensors that could help prevent falls.

“It will be wonderful to have space for older adults to try out and test wearable devices and sensors that are being developed to monitor their health,” says Dehak, who is a leader of the technology core of the Johns Hopkins University Claude D. Pepper Older Americans Independence Center at Johns Hopkins Bayview, which was launched in 2003 and recently received a five-year renewal of federal funding.

The Secrets in Our Cells

Of course, biological processes are key to aging, and toward that end, some of the most exciting work coming out of the Human Aging Project is happening at the cellular level, as HAP researchers tease out just what goes wrong as our cells age.

Consider the research of cell biologist Hiromi Sesaki, the Karen and Ethan Leder CIM/HAP Scholar, who focuses on the “mighty mitochondria” — the powerhouses of our cells, which toil away to give our heart and brain and lungs the energy they need to function effectively. To do that work, the mitochondria are constantly dividing in a crucial process that “serves as a type of ‘quality control’ within the cell by removing damaged mitochondrial DNA that accumulates,” explains Sesaki.

This damage removal process is known as mitophagy. And as we age, our mitochondria become less adept at mitophagy — at removing the “trash” (DNA mutations and deletions) and other toxins that accumulate in our cells.

Sesaki and his lab are zeroing in on the biology of the mitophagy process. “We hypothesize that decreased mitophagy contributes to reduced mitochondrial health during aging, leading to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s,” he says. But there’s a bright side, he notes: “We also think that enhancing the mitophagy process could allow us to slow — or even reverse — some of the ravages of human aging.”

Ultimately, Sesaki and his colleagues aim to provide insights to allow for the future development of drugs “that could target cellular mitophagy to improve the quality of life during aging — and therapeutic interventions for neurodegenerative diseases,” he says.

Age-related frailty, both physical and cognitive, is another key area of study for HAP researchers. Two recent studies led by Abadir, associate professor of medicine in the Division of Geriatric Medicine, are particularly exciting. His team’s findings lay the groundwork for developing blood tests that could identify individuals at risk of physical and cognitive decline, potentially leading to earlier and more effective interventions.

In the first study, involving more than 600 adults, Abadir and his team discovered that higher levels of circulating cell-free DNA (ccfDNA) in the bloodstream may serve as a warning sign for dementia and frailty. These DNA fragments, released during natural cell death, can trigger chronic inflammation — a key factor in tissue and organ degradation, including the brain. This study was published in the Journal of Alzheimer’s Disease in October 2022.

Building on this research, Abadir’s subsequent study expanded the focus to mitochondrial DNA fragments. Unlike genomic DNA, which is inherited from both parents, mitochondrial DNA, found in the “power plants” of cells, is maternally inherited. This new study, which Abadir conducted with Lolita Nidadavolu, assistant professor of medicine, was published in Immunity & Ageing in June 2023. It showed that higher levels of mitochondrial DNA fragments in the blood are closely linked to chronic inflammation and physical decline. This provides further evidence, the researchers say, that these DNA fragments could serve as reliable biomarkers for aging.

Interestingly, notes Abadir, while both genomic and mitochondrial DNA fragments were associated with cognitive and physical decline, “the mitochondrial DNA was more strongly linked to physical deterioration.” This distinction highlights the potential for more targeted interventions to prevent frailty and preserve quality of life in older adults, he says.

“The implications of these findings are profound,” says Abadir. “With a simple blood draw, it may soon be possible to detect the earliest signs of aging-related decline, allowing for timely interventions that could extend the health span of millions of people.”

Don Willett October 30th, 2024

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10. Easing Isolation for Better Health

10. Easing Isolation for Better Health

Johns Hopkins geriatrician Thomas Cudjoe remembers his disbelief when he discovered that many of the older East Baltimore adults participating in his “Ask the Doctor” talk had never met some of their next-door neighbors.

“They shared that they didn’t really feel connected to one another or the community. They didn’t really engage with people outside of their building. It puzzled me that these people lived so close to one another but, for whatever reason, didn’t feel connected,” says Cudjoe, who is the Caryl & George Bernstein CIM/HAP Scholar.

So Cudjoe set out to explore the health risks of social isolation, especially for those who are aging. Although many scholars have discussed the effects of individual loneliness, he says, few examined how the phenomenon of social isolation might contribute to higher levels of illness and even death.

It’s a critical question given that one in four Americans aged 65 or older who are living in a community experiences social isolation, according to his research.

Among his various studies, Cudjoe has investigated how social isolation may lead to elevated inflammatory biomarkers in older adults as well as how isolation can increase one’s risk for functional decline. And last year, he published a report in the Journal of the American Geriatrics Society suggesting that social isolation may influence whether older people develop dementia. In a nine-year study of 5,022 Medicare beneficiaries who were community dwelling, Cudjoe and colleagues found the risk of developing dementia was 27% higher in those people who were socially isolated.

Cudjoe believes that clinical screening to identify social isolation may help older adults take steps to become more socially connected in order to maintain their physical and mental health. Since COVID-19 brought national awareness to the dangers of social isolation, he says, more researchers are developing novel programs and interventions to help to decrease it.

Cudjoe is also pushing to develop home-based solutions for his patients by working with School of Nursing researchers who use the Community Aging in Place — Advancing Better Living for Elders (CAPABLE) program. The brainchild of School of Nursing Dean Sarah Szanton, CAPABLE earned a prestigious Heinz Award in 2019.

Cudjoe is grateful to CIM and the Human Aging Project for encouraging such cross-disciplinary collaborations. “The CIM has been a great incubator of my ideas,” Cudjoe says. “It also continues to be a source of innovation and inspiration.”

Don Willett October 30th, 2024

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11. Music-Making for Measurable Gains

11. Music-Making for Measurable Gains

Johns Hopkins neurologist Alexander Pantelyat is exploring ways to use one of the world’s oldest healing therapies to improve the lives of patients confronting such debilitating neurodegenerative diseases as Parkinson’s and Alzheimer’s.

Supported as the Alafouzos Family CIM/HAP Scholar since 2021, the physician/violinist aims to make music and rhythm an integral part of treating aging-related illnesses.

Already, his studies have demonstrated that singing can help mood, speech and quality of life in patients with Parkinson’s disease. And in a study of patients with Parkinsonian disorders and poor gait, he showed that walking to a marchlike beat improved walking — even after the music stopped.

Another innovative study, supported by a generous donation from Anne and Eugene Fife, is evaluating the benefit of music therapy for patients with mild cognitive impairment and mild dementia due to Alzheimer’s disease in their homes. In virtual music therapy sessions intended to stimulate their autobiographical memory, participants first listen to their favorite piece of music, such as Frank Sinatra’s “My Way.” Then they listen to a scrambled version of the piece as well as to a song that is similar but lacks personal meaning for them.

MRI testing looks for differences in brain connectivity before and after the eight-week study. Pantelyat and his team are looking for improvements in patients’ memory, mood and well-being, and they are testing whether the MRI findings can help explain which participants are more likely to benefit from music therapy.

“Previous studies have suggested that exposure to music even for a short period of time could lead to measurable changes in the brain,” Pantelyat says. “We’re seeing how various networks of the brain respond to music and how that could potentially link back to improving memory loss.”

Justin McArthur, director of the Department of Neurology and a member of the CIM Committee, points out that the CIM/HAP scholarship has been instrumental in supporting Pantelyat’s work at Johns Hopkins, as well as the work of vascular neurologist Elizabeth Marsh, the Rubenstein Family CIM Scholar.

Says Pantelyat, “The CIM support has tremendously accelerated our pace of discovery and enabled us to take on several key projects that would otherwise have been delayed or may not have moved forward at all!”

Don Willett October 30th, 2024

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12. Deepening the Dialogue in Advance Care Planning

12. Deepening the Dialogue in Advance Care Planning

Most of us think of advance care planning as simply filling out a form designating someone to make health care decisions when we can’t and expressing our general wishes about the decisions we hope they’ll make on our behalf.

But for Jessica Colburn, who in 2019 was named the Mary Gallo CIM Scholar to support her innovative work in geriatric medicine, advance care planning is so much more: a unique opportunity to deepen the dialogue between aging patients and their primary care providers.

“I like to think of it as part of a continuum of thinking,” she says. “What is important to me in my health care? How am I making choices with my primary care provider about my health care? And, ultimately, if I couldn’t speak for myself, who would I want to make those choices for me?”

An associate professor of medicine in the Division of Geriatric Medicine and Gerontology, Colburn came to Hopkins as a trainee in 2005 and joined the faculty in 2011 because “geriatrics was embedded in the curriculum and the fellowship, and because there was such a strong focus, led by David Hellmann, on the importance of knowing your patients as people,” she says.

It’s a focus that has always informed Colburn’s work as a clinician and educator, and it is essential to her research into issues like advance care planning. Most recently, she helped lead a clinical trial that examined the process of initiating the advance care planning conversation.

“It’s a difficult conversation for many patients to have,” she says, “and its success depends on a relationship developed over time, on primary care providers and teams really knowing their patients and understanding not only their health care needs, but their personal values and health care priorities.”

As director of the Johns Hopkins Geriatrics Fellowship program and co-director of the Johns Hopkins Topics in Geriatric Medicine course, Colburn mentors medical students, residents and fellows, and has won multiple excellence in teaching awards. And as director of the federally funded Johns Hopkins Geriatric Workforce Enhancement Program, she has worked for years educating and collaborating with primary care providers in the larger Baltimore community who serve older adults.

“I get to do a lot of wonderful things as a program director,” Colburn says. “But Mrs. Gallo’s investment in me and my career has given me the luxury of protected time to study the effectiveness of the things I do. It’s been an incredible opportunity.”

Don Willett October 30th, 2024

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13. Pioneering Dramatic Advances in Patient Care

13. Pioneering Dramatic Advances in Patient Care

Alfredo Quinones-Hinojosa is a world- renowned brain surgeon whose research in finding better treatments for brain cancer has dramatically improved life for thousands of patients. Holder of more than a dozen patents, he has started several companies to translate his labwork back to the patient.

And there is even more hopeful news on the horizon.

Earlier this year, he and colleagues at Mayo Clinic published details of a biospecimen repository they have developed — the first of its kind in the world — that promises to unlock new insights into brain cancer and to speed treatment advances through new collaborations and clinical trials.

For Quinones-Hinojosa, the repository marks the culmination of a career-long quest (see box) that got its start at Johns Hopkins. As a young physician-researcher, he led the Brain Tumor Surgery Program at Johns Hopkins Bayview as well as the Brain Tumor Stem Cell Laboratory. It was during these years that he came into the orbit of David Hellmann and the Center for Innovative Medicine, when the clinician-scientist was invited to Hellmann’s office for early-morning leadership gatherings.

“I felt so blessed at the time to be part of something so spectacular,” says Quinones-Hinojosa. “We talked not just about leadership but about health care and politics, about the future not just of Johns Hopkins, but of medicine itself.”

Quinones-Hinojosa also shared with Hellmann his hopes and dreams for building a biospecimen laboratory that could revolutionize treatment for brain cancer and other neurological disorders. This was in the first decade of the new millennium, before today’s advances in high-speed data gathering and artificial intelligence.

“We were getting brain tissue samples from patients in the OR, but we weren’t able to collect and analyze other vital clinical data, such as imaging studies, family history, pathology reports, social history,” says Quinones-Hinojosa. “It was like trying to navigate the sea without a compass.”

Crucially, he says, Hellmann recognized the incredible promise of his ambitious quest — to create a biospecimen repository that would bridge the OR with the basic science laboratory — and provided CIM funding that proved pivotal to getting the biorepository off the ground.

Quinones-Hinojosa left Johns Hopkins in 2016 to join Mayo Clinic as the William J. and Charles H. Mayo Professor and Chair of Neurologic Surgery, and to direct the Neurosurgery Brain Tumor Stem Cell Laboratory, where his vision would ultimately come to fruition.

“The Mayo Clinic got a tree complete with leaves and branches,” says Quinones-Hinojosa, now the James C. and Sarah K. Kennedy Dean of Research at Mayo Clinic in Florida.

“But David Hellmann got a seed. He had to plant it and water it — and that ‘watering’ was the financial support for what today has become the most prominent biobank in the world for human tissue linked with data.

“None of this would have happened,” says the esteemed neurosurgeon, “without that seed being watered and planted back then.”

Always Breaking New Ground

Quinones-Hinojosa’s experience is hardly an isolated one. Time and again, over these past 20 years, Hellmann has identified physician-scientists with pioneering ideas, and CIM donors have generously come through with funding to jumpstart their pathbreaking research. The pay-off for patients at Johns Hopkins — and beyond — has been significant.

Consider those suffering from vasculitis, an autoimmune disease that causes inflammation of the blood vessels. Rheumatologist John Stone, who received early funding from CIM as a Cosner CIM Scholar in Translational Research, pioneered a game-changing new treatment, called rituximab, for a common form of the disease (ANCA-Associated Vasculitis HRAVe). Since the breakthrough was first published in The New England Journal of Medicine in 2010, rituximab has become the treatment of choice for vasculitis patients the world over, in what has been hailed as one of the most important advances in rheumatology in the 21st century. Stone, who co-founded the Vasculitis Center at Johns Hopkins, is now director of clinical rheumatology at Harvard’s Massachusetts General Hospital.

Rheumatologist Antony Rosen has served as vice dean for research at Johns Hopkins Medicine since 2013 and as director of the Division of Rheumatology from 2002 to 2022. Under his leadership, the division grew from 14 to 26 faculty and began its run of being ranked #1 in the country by U.S. News — now extended under Director Ami Shah — for 21 years in a row.

He’s seen firsthand the impact that CIM funding has had in advancing bench-to-bedside research in key areas.

“David Hellmann is an iconoclast at heart. He is always wanting to break new ground,” says Rosen. “To do that, he is focused on identifying the best young researchers with the best ideas — and keeping it tied to what really matters to real patients.”

Pulmonologist Michelle Sharp, a Mary Gallo CIM Scholar, can attest to that. Since joining the faculty at Johns Hopkins Medicine five years ago, she has led efforts to improve care for individuals living with sarcoidosis, a difficult-to-diagnose inflammatory disease in which the immune system overreacts.

While 90% of patients with sarcoidosis experience inflammation in their lungs, the condition can also impact the heart, eyes, nervous system, kidneys, bones, joints and skin. Every person with sarcoidosis is affected differently.

Sharp quickly moved to strengthen the multidisciplinary approach of the Johns Hopkins Sarcoidosis Program, which today cares for more than 2,000 patients a year. She’s also launched efforts to address disparities in care through new patient education efforts and established a Patient Advisory Board and Patient Support Group. “As we have been building our capacity, it has been so important to me that we hear from our patients so that we can learn firsthand their needs and the challenges they face,” she says.

The research side of Sharp’s work has gotten a significant boost from her CIM Scholar funding from Mary Gallo and also from the late Everardo and Elena Goyanes, she notes gratefully. She and her colleagues are building a biorepository holding patient data and biological samples. “Working together as a team,” she says, “we are well positioned to solve the mysteries that have remained in sarcoidosis for more than 100 years.”

For Johns Hopkins gastroenterologist Pankaj “Jay” Pasricha and psychiatrist Glenn Treisman, CIM funding enabled them to launch what was considered to be the first clinic in the world that brings together gastrointestinal and psychiatric experts to treat patients in both physical and psychological distress. Established in 2014 thanks to a generous gift from Courtney and Paul S. Amos, the Amos Food, Body and Mind Center has focused on studying the links between diet and disease, and also the role of good and bad bacteria in making us sick and keeping us healthy.

“People have talked about the gut-brain connection for a long time, but usually in the context of people who are depressed or anxious and, as a result, have physical symptoms. But that’s not the whole story,” says Treisman. “We are emphasizing that this is bidirectional. Signals emanating in the gut can influence how the mind feels.”

He estimates that close to 600 patients have come to the Amos Center for treatment — “complicated patients” who have been struggling for years to find relief. “We helped a lot of these people get better,” he says.

Well-Placed ‘Bets’

Bruce Bochner was already a professor of medicine and division chief, leading the Division of Allergy and Clinical Immunology at Johns Hopkins Bayview, when he received CIM funding as the CIM Cosner Scholar in Translational Research.

“The support that I received from CIM toward my salary was almost as good as having an endowed chair. It allowed me to do all the administrative things I needed to do as division chief and also see patients and do research in a way that was very impactful. That ability to wear all three hats at once was extremely important,” he recalls.

Wearing his physician-scientist hat, Bochner focused on advancing his research to find therapeutic targets for patients suffering from allergic and allergic-like conditions — ranging from gastritis to eczema to hives — caused by a problematic build-up of eosinophils (a type of white blood cell) and mast cells. Ultimately, he zeroed in on a surface protein called Siglec-8, developing an antibody that was licensed by Johns Hopkins to a start-up company, Allakos, with Bochner as co-founder.

Bochner left Johns Hopkins in 2013 to return to his hometown of Chicago, becoming the Samuel M. Feinberg Professor at Northwestern University School of Medicine’s Division of Allergy and Immunology. Once there, his work with Siglec-8 continued, hitting a high-water mark with a successful phase 2 clinical trial reported in The New England Journal of Medicine in 2020. More recently, Allakos, where Bochner continues to consult, has shifted its focus to a mast cell-specific target, Siglec-6.

“For me as a physician-scientist, the dream is to work on a project that somehow changes the way we diagnose and treat patients,” says Bochner, now professor emeritus at Northwestern. “It’s been a real thrill for me to have co-discovered and co-founded aspects of projects that have the potential to help many patients.”

Early support from CIM, he says, was crucial to his journey in academic medicine — and that of so many other physician-scientists at Johns Hopkins. “David Hellmann has an uncanny ability to place bets on people he thinks will not only succeed in various aspects of academic medicine, but also help them to go above and beyond what they are already accomplishing,” says Bochner. “CIM’s support enables them to thrive.”

Don Willett October 30th, 2024

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