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.”