For Dr. John Sedivy, Hermon C. Bumpus Professor of Biology, the study of molecular biology and genetics offers answers to life's big questions on its smallest scale. "I think real creativity comes from an intuitive understanding of how biology works and how things are connected. You're always making baby steps and then using the evidence to direct your future steps." Sedivy says he has stayed with that approach throughout his career.
He started working on cancer, then moved to cell biology and an area known as senescence—a form of cell death. "I have a pretty good track record of being able to find new things," says Sedivy. "Most recently, we discovered a process where viral-like elements that inhabit all of our cells become activated during aging." These elements are troublemakers by design, and they have a devastating impact on some very common age-related diseases.
Old drugs, new tricks
In addition to studying the causes and mechanisms of aging, researchers at Brown's Center on the Biology of Aging focus on the intersection of age-related diseases and how we might treat them. This field is what the National Institutes of Health calls geroscience, and to explore it, Sedivy collaborates—a lot.
In partnership with Dr. Gideon Koren, professor of medicine and director of the Cardiovascular Research Center at Rhode Island Hospital, Sedivy discovered that the heart actually contains senescent cells (fibroblasts, among others) which influence the functioning of the entire organ and may be responsible for sudden cardiac death. "Together, we came up with a completely new idea for how this disease could be treated, and we now have a multiyear, multimillion-dollar grant from the National Institutes on Aging to investigate our theory."
Early in 2019, Sedivy published a paper about cell senescence and how it can be regulated with certain drugs that are typically used to treat HIV. Then, with Dr. Stephen Salloway, Martin M. Zucker Professor of Psychiatry and Human Behavior and professor of neurology, Sedivy received a grant from the Alzheimer's Association to conduct a clinical trial with one of these drugs, which could reduce brain inflammation in Alzheimer's patients.
Senescent cells also promote the deterioration of joints, which manifests as osteoarthritis. Sedivy and Dr. Qian Chen—Michael G. Ehrlich, MD, Professor of Orthopedic Research and professor of medical science—share a patent on the use of a class of HIV drugs, reverse transcriptase inhibitors, to treat osteoarthritis. It was a "new direction, a new class of drugs that had never been thought of as a treatment for osteoarthritis," says Sedivy. "It was completely unexpected."
Survival of the fittest
“Most people are concerned with living better in old age,” says Sedivy, so he hopes that his research can improve people's quality of life. "Aging well is very straightforward," he says. "It means surviving to very old age, remaining active, avoiding frailty, and being free of major chronic diseases like Type 2 diabetes, cancer, cardiovascular disease, and dementia. The amazing thing is that we all know people like that ... [and] we know that their biology has allowed them to lead that type of life. We just have to understand them, and then we'll all share it."