Geroscience

Medical care for older adults didn’t become a distinct practice until the dawn of the 20th century—a time, it is worth noting, when the average life expectancy in the United States was roughly 47 years. It emerged in part from the differing points of view of two medical pioneers: Élie Metchnikoff, a Russian microbiologist, and Ignatz Nascher, MD, who received his medical degree from New York University School of Medicine and later became New York City’s chief physician.

Metchnikoff coined the term gerontology, the study of aging, in 1903, and later won the Nobel Prize in Physiology or Medicine. Focusing on immunology, he developed the theory that aging is caused in part by toxic bacteria in the gut, and he recommended daily consumption of yogurt to extend life.

Nascher had a different hypothesis. Based on his experiences with patients, some of whom lived in almshouses, he believed that natural death results from the decay of the body’s organs and that the length of a person’s life depends in large part on their “mode of living,” including their diet. In 1909, Nascher set out to distinguish the medical treatment of older adults and coined the term geriatrics (from the Greek geras, meaning old age, and iatrikos, meaning physician).

Both terms stuck. Geriatrics has become a specialty for physicians, and gerontology has become a fast-evolving area of study for medical scientists and health professionals. These complementary domains—and the intersection of microbiology and medical practice—are now critically important because the world’s population is rapidly aging. Over the last decade, more than 10,000 Americans have turned 65 each day—a trend that is projected to continue until 2030.

To address this wave of older adults, leaders in geriatrics and gerontology at Yale School of Medicine (YSM) say that nothing less than a revolution in medicine for older adults is underway. Advances in the understanding of the biological mechanisms, syndromes, and diseases of aging are enabling physicians to extend healthy lifespans, giving patients the power to choose their quality-of-life priorities, and perhaps even to slow the aging process.

“Formerly, the focus was on extending life,” says Thomas M. Gill, MD, Humana Foundation Professor of Medicine (Geriatrics). “Now, we don’t want people to just live longer; we want them to live longer and healthier. That’s why we talk about ‘health span’ rather than ‘lifespan.’”

The revolution in care for older adults came about in part because of discoveries that identified some of the fundamental mechanisms of aging at the cellular or organismal level. These mechanisms, including metabolic changes, inflammation, epigenetics (heritable traits that occur without changes to the DNA sequence), and protein regulation, are now known within the scientific community as “hallmarks of aging.”

At Yale, one of the key research topics is geroscience, a field in which scientists explore the biological mechanisms of aging and use that knowledge to develop interventions that can delay the onset of age-related diseases. Last year, Yale launched a Translational Geroscience Initiative that funds cross-disciplinary research and brings visiting professors to campus. The recipient of the first research award was Daniel Jane-Wit, MD, PhD, associate professor of medicine (cardiology) and immunobiology. His project explores the molecular underpinning of the aging of blood vessels.

The first visiting professor was Luigi Ferrucci, MD, PhD, a geriatrician and epidemiologist who is the scientific director of the National Institute on Aging. Ferrucci is best known for refocusing the landmark Baltimore Longitudinal Study of Aging to explore the geroscience hypothesis, which posits that it is possible to delay or prevent the onset of multiple age-related diseases and extend the healthy lifespan by targeting the biological mechanisms of aging. The hypothesis suggests that aging itself is the major risk factor for chronic conditions like heart disease, diabetes, and Alzheimer’s, and that interventions slowing the aging process could have widespread health benefits.

In 1983, Yale recognized medical treatment for older adults as a distinct discipline by establishing geriatrics as a subsection within general medicine; it became a section within the Department of Internal Medicine in 1999 with Leo M. Cooney, Jr., MD, now Humana Foundation Professor Emeritus of Medicine (Geriatrics), as the first section chief. Since that beginning, Yale faculty members have stood at the forefront of many initiatives and discoveries in the field.

Mary Tinetti, MD, Gladys Phillips Crofoot Professor of Medicine (Geriatrics), who headed the geriatrics section for many years, is now leading a national effort called Patient Priorities Care, which seeks to transform the way geriatric medicine is practiced. Instead of physicians treating individual diseases of aging in isolation, Tinetti calls on physicians not only to treat patients’ diseases holistically but also to discover the goals of each patient to personalize their care decisions. “It begins with a conversation with the patient,” Tinetti says. “You start with the individual’s goals, not by focusing on the disease or the organ.”

Several Yale faculty members also have produced innovations addressing “syndromes of aging,” such as falls, delirium, and functional decline, among others. Gill, Tinetti, and their colleagues observed that these syndromes have multiple risk factors and multiple consequences—many of which share the same causes and effects. Recognizing this pattern, the faculty members designed interventions aimed at forestalling the onset of such syndromes and helping people recover from them.

Similarly, it’s well established that several major diseases are age related, including cardiovascular disease, cancer, arthritis, type 2 diabetes, hypertension, and Alzheimer’s disease. Even though these diseases don’t occur solely in older people, their incidence increases exponentially with age. In addition, some infectious diseases, among them COVID-19 and West Nile virus, take a greater toll on older adults.

To better understand the barrage of health risks facing older adults, much of the research at Yale seeks to identify the actual mechanisms of aging that contribute to age-related diseases. For example, Vishwa Deep Dixit, DVM, PhD, Waldemar Von Zedtwitz Professor of Pathology and professor of immunobiology, focuses on the role of inflammation in the diseases of aging. His lab helped establish that age-related inflammation can trigger chronic diseases; the team further demonstrated that reducing calorie intake can curb inflammation and potentially forestall the onset of disease.

Meanwhile, Ruth Montgomery, PhD, professor of medicine and professor of epidemiology (microbial diseases), researches the effects of aging on the immune system. She and her colleagues have studied the role of natural killer (NK) cells—the white blood cells we count on to fight off infections—in defeating West Nile virus. With close colleague Albert Shaw, MD, PhD, professor of medicine (infectious diseases), they also study how aging reduces the effectiveness of innate immune cell types and responses to vaccines. The end goal for much of this research is discovering methods for slowing the effects of aging on immune function. “If you can delay the process of aging, you can address the associated diseases, too,” Montgomery explains.

Until very recently, scientists believed that nothing could be done medically to slow the body’s tendency to decline with age. However, studies of the molecular mechanisms underlying aging indicate that by influencing those cellular processes, we may be able to slow the inherent physiological changes and live longer, healthier lives.

Researchers at Yale also are exploring the potential of senolytics, a new category of therapeutics designed to reduce aging’s ill effects on cells. The idea is that if we can remove senescent cells from the body—the ones that have deteriorated—the remaining cells will be healthier and function better. To venture into this area of research, medical scientists are focusing initially on therapies that have already been approved by the U.S. Food and Drug Administration and repurposing them to address health in older individuals. An example is dasatinib (Sprycel), which is used to treat certain types of leukemia and is now used also as a senolytic. At the same time, investigators are doing early investigations that may produce novel senolytic therapies not yet approved for any medical use that may someday be available to patients.

The search for answers is all the more urgent, considering that there are only about 8,000 geriatricians in the United States today—not nearly enough to treat the more than 58 million Americans who are age 65 or older. That’s why Yale School of Medicine, in addition to training geriatricians, embeds the principles of personalized holistic geriatric care into its medical school and residency programs.

As part of this training model, all Yale residents rotate through the Acute Care for the Elderly Unit in Yale New Haven Hospital. There, the attending physicians impress on residents the importance of listening to patients’ stories and understanding their priorities. “Residents see the radical opposite of doing disease- or organ-based decision-making,” says Terri Fried, MD, Humana Foundation Professor of Medicine (Geriatrics) and section chief for geriatric medicine. “This will have a profound effect on how they think about care for older patients throughout their careers.”

To sum up the collective impact of Yale’s intense focus on aging, Gill says, “We’re all invested and committed to having Yale be a top institution for the entire continuum of aging research. And we’re well on the way to making that happen.