YCCI’s renewed CTSA grant award allows Yale to continue its leadership in cutting-edge areas of research. One such novel initiative under the grant renewal is Diseases Across the Lifespan, which will explore the rising field of lifespan research—a new approach to examining the ways in which diseases that commonly strike adults have their roots in infancy and early childhood.

A trio of physician-researchers who are experts on both ends of the lifespan leads the new initiative:

• Clifford W. Bogue, MD, Professor and Chair of the Department of Pediatrics
• Thomas M. Gill, MD, the Humana Foundation Professor of Medicine (Geriatrics) and Professor of Epidemiology (Chronic Diseases) and of Investigative Medicine, and Director of the Yale Program on Aging and of the Claude D. Pepper Older Americans Independence Center
• Linda C. Mayes, MD, the Arnold Gesell Professor of Child Psychiatry, Pediatrics, and Psychology; and Chair of the Yale Child Study Center.

Lifespan research seeks to recognize risk factors in early childhood that can cause problems later. “We are looking at a lifespan perspective on how diseases emerge,” says Mayes. Doing so opens the door for earlier diagnosis and intervention, and the capacity to lessen the impact of disease as people age. “We talk about how biology is adapted to a given period or context, but then becomes a disease later in life.”

“Sometimes, the die is already cast when someone enters old age from events that occur earlier in life,” says Gill. “The aging process operates from the beginning of life. There are many biological, social, environmental, and clinical issues that are of great importance, and there are a lot of unanswered questions.”

While the leaders of this new initiative have yet to determine particular diseases of interest for lifespan research at Yale, one obvious candidate is obesity. “We know that our society is becoming increasingly obese, and there are some startling statistics about the high rates of obesity in childhood as well as the increase in metabolic conditions such as diabetes,” says Gill. Obesity is also a strong candidate for lifespan research because of its link to diabetes and such other conditions as heart disease.

Addressing these conditions more deliberately and earlier in life may not only improve a patient’s health, but also has the potential to reduce the high health care costs related to treatment of chronic disease in the long term. “By making the right intervention earlier and diagnosing it properly, we can have a huge impact on our national health picture,” says Bogue.

The diseases that will ultimately be chosen will harness Yale’s current strengths in a variety of areas. “Historically, Yale has been one of the leading institutions studying diabetes and metabolism, with considerable expertise in childhood diabetes, and increasingly, old age,” says Gill.

Lifespan research may also broaden understanding of how stress in childhood may be linked to adult disease. “In child mental health, one of the most compelling questions is how early stress and adversity, defined not just as child abuse or neglect, but family alcoholism, or profound family stress, break up, or exposure to war, can regulate a child’s stress system,” says Mayes. “We are just beginning to learn that those individuals that appear in our internists’ offices at age 40 with serious heart disease are often the individuals that are more likely to have had these early kinds of stressors in childhood.”

Yale has a reputation for robust collaboration between a variety of departments, and the new initiative also has the capacity to spawn ever more collaborative efforts between disparate departments. “In many places where departments are siloed, we have people who are willing to work collaboratively because they want to find answers,” says Bogue.

“Lifespan research provides a much broader perspective, and opens up many new avenues for scientific inquiry and opportunities to collaborate,” says Gill. “I think that that is one of the important objectives of this new initiative—to foster and promote collaborations between investigators who have been focusing their research on a specific segment of the lifespan.”

Collaborations between pediatricians and internists, however, are less common, and lifespan research aims to change that. “When we do get together, we realize we have more in common than not,” says Gill. “There are a lot of issues involving caregivers, for example, which are common between the populations. There are also issues relating to cognitive capacity. Judgment doesn’t often become fully developed until someone is 25, and we often start losing our cognitive and physical capacity as we get older.”

Lifespan research seeks not only to examine the impact of disease within the life of an individual, but also to examine how factors that influence health can be transmitted from one generation to the next. The field aims to understand how adults can affect children’s development, and how children’s development affects adults in turn through the parenting relationship. “In the act of being a caregiver, we know that caring has potential psychological as well as health benefits,” says Mayes. “Is the role of being a primary grandparent health-promoting? For me, being able to take this lifespan perspective, not just on disease but on health, on how things are transmitted generation to generation, is incredibly exciting.”

In the United States, lifespan research is still an emerging field. To date, most of the work in the field has come from the United Kingdom, where the discipline is known as life course research. University College London, a partner institution of Yale with strong connections to the Yale Child Study Center and the Program on Aging, has many resources in the field that Yale can look to, says Gill. In some ways, the United Kingdom is ideally positioned to conduct research across the life of an individual because of the existence of a national health service; the infrastructure is already in place to enroll an entire generation into a birth cohort study. Part of the challenge of building a lifespan research initiative at Yale would be to determine how to proceed without built-in birth cohorts. This goal can be achieved, says Mayes. “Lifespan studies require investment and some creativity,” says Mayes.

Although the initiative is in its very early stages, its leaders have begun to investigate the best direction to take. “At this point, we are brainstorming about the best opportunities in which Yale is positioned to take a leading role,” says Gill. These initial meetings have already led to a new pilot RFA and the development of the new Gesell Lifespan lecture series launched in April 2017 with its inaugural visiting scholar, Steve Suomi, PhD, currently Chief of the Laboratory of Comparative Ethology at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. During the visit, Suomi met with the lifespan team and gave several lectures to students, trainees, and faculty focused on multi-generation studies among rhesus monkeys reared under a range of different conditions.

Plans are also underway to develop a registry service to support lifespan research with linked biologic samples. “There’s an amazing depth of expertise both in basic science and in clinical translational areas that will provide a very strong foundation for our initiatives,” says Bogue.

“Yale has been a leader in child/adolescent research with the world-renowned Yale Child Study Center; at the other end of the aging spectrum, the Yale Program on Aging/Claude D. Pepper Older Americans Independence Center is focused on research directed at enhancing the independence of older persons,” says YCCI Deputy Director Melinda L. Irwin, PhD, MPH. “YCCI can and should coordinate research and training efforts between these centers and other Yale centers/programs, with a focus on translational research that can ultimately shape policies that impact the entire lifespan.”

“I think YCCI is the logical vehicle to bring investigators together to advance this type of initiative,” says Gill. “YCCI can help provide the infrastructure that others who are working in this area can leverage, and ideally provide incentives so investigators in different disciplines will come together.”