The Institute on Aging (IOA) at the University of Pennsylvania is pleased to introduce our new Associate Director, F. Bradley Johnson, MD, PhD!
In addition to this new title, Dr. Johnson is also an Associate Professor of Pathology and Laboratory Medicine at the University of Pennsylvania. His research is focused primarily on the biologies of telomeres, genome stability, and cellular senescence, and how they impact age-related diseases. Dr. Johnson’s clinical duties include serving as Assistant Director of the Clinical Immunology Laboratory at the Hospital of the University of Pennsylvania, where he helps oversee tests facilitating solid organ and bone marrow transplantation. Related to these clinical activities, he is also investigating roles for the major histocompatibility complex in the regulation of RNA biology and Alzheimer’s disease.
Prior to joining the Department of Pathology and Laboratory Medicine here at Penn, Dr. Johnson earned his MD and a PhD in biochemistry from Stanford Medical School in 1995, followed by a residency in clinical pathology at Brigham and Woman’s Hospital at Harvard Medical School and postdoctoral research at the Massachusetts Institute of Technology.
Learn more about Dr. Johnson’s research interests and plans for the IOA in our Q&A here!
Q: How did you first get involved with the Institute on Aging?
A: I first learned about the IOA form John Trojanowski and Virginia Lee when I was interviewing for faculty positions back in 2001. The fact that Penn had such a well-established and active aging institute was one of the key features that attracted me to join the university.
Q: What goals do you hope to achieve as the new Associate Director?
A: First, I hope to learn more from current IOA leaders, particularly John Trojanowski and Kathy Jedrziewski, about how they run things, and where they see problems and opportunities for growth. Second, I’d like to see how we might enhance interactions among people studying features of aging at Penn in disciplines that have traditionally been considered separate. We have a remarkable breadth of expertise, and an unusually collegial environment, so there are many opportunities for cooperation. Finally, I’d like to expand our efforts to inform the public about new findings in gerontology, and to involve them in debates on related issues.
Q: How has your thinking about aging changed over the years?
A: Quite a bit. I first began to wonder about how aging happens when I was a young kid. Some of my great-grandparents and grandparents were lucky enough to live to exceptional ages with few health problems and I wondered what explained their good fortune. My mom’s mom’s mom, who i got to know well, was given a ceremonial cane by the town government in recognition of her 100th birthday, and the newspaper reported her remark that what she’d really have enjoyed was a motorcycle and that upon leaving the ceremony she carried the cane in a fashion that conspicuously avoided it touching the floor! At the same time, other family members and older friends were suffering from various age-related problems, and it started to become apparent to me how much aging increases the risk of many different diseases and, ultimately, death. As a kid, it was the death aspect that really got my attention, but as I came to recognize and accept the transient nature of all things, I became increasingly motivated by the idea that the more that people understand how aging works, the better we can minimize its negative impacts. I thought aging would be a great problem to tackle – to me it’s a manifestation of the very human drive to improve the situation of oneself and others, and I thought (and still think) it’s a good bet that the more people can understand and slow aspects of aging, the more we can enhance wellbeing.
Even by the time I got to college and graduate school, in the mid 1980s, aging was still broadly considered to be something that was fundamentally unalterable, because it was thought to be a simple manifestation of entropy – in other words, just like any complex system, biological molecules, and tissues have a tendency to fall apart over time. For a number of reasons, this viewpoint never made sense to me, and indeed it started to become apparent from studies in model organisms in the 1990s that simple genetic or dietary interventions could dramatically extend lifespan which, importantly, was accompanied by improved health overall. For my postdoctoral work, I was fortunate to join Lenny Guarente’s lab at MIT because it was genuinely focused on investigating the molecular genetics of aging. It was a stimulating and fun environment, and the early successes in the field at the time raised hopes that aging might not be so hard to understand and control. Today, I believe aging is in fact complicated – it involves lots of little problems that affect different people to various extents, and which can sum into bigger problems. All of these problems can be addressed in principal, and indeed great strides are being made, but there’s no single “magic bullet.” Mostly, I think of aging as something that changes individual strengths and weaknesses over time. I hope that by understanding more about how aging works, we can expand the tools available for people to use as they wish to enhance their own happiness.
Q: What do you find most interesting and/or challenging about the field of aging?
A: Worldwide, people are living to older ages than ever before. This is because we’ve made progress in solving many of the problems that have plagued people for most of our history – especially starvation, infectious disease, political instability and violence, and, more recently, cardiovascular disease and cancer. Therefore aging has become one of the ultimate barriers to physical health. You can do everything possible to follow a healthy lifestyle, and if – like most people these days, you avoid death by things like automobile accidents, natural disasters or violence – you will get old, likely get sick, and will most certainly die. Aging is now the biggest risk factor for most of the diseases that still affect us. The challenge now is to understand the details of how aging does this so as to minimize disease.
Q: What do you think are the most important issues that need to be addressed in the area of aging right now? And how, if at all, do you see this evolving in the next several years?
A: One important issue is to extend the successes the aging research community has had in model organisms, e.g. flies and mice, to human biology. It’s become apparent that there are some conserved mechanisms impacting aging, that is, there are biological processes that operate similarly in different species to regulate the pace of aging. However, aging mechanisms are freer to vary between species than many other biological mechanisms, because they evolve due to a decline in the force of natural selection as individuals get older (this is because these mechanisms are manifest after genes have already been passed on to offspring, and so the die is cast for genes that have negative impacts only later in life). In other words, important aspects of aging will be different in different species, and so if we really want to understand how human aging works, we can’t rely solely on model organisms, and ultimately we have to study it in human systems. Fortunately, the tools for doing this type of work are developing rapidly, e.g. growing human tissues in culture or using new bioinformatics tools to study the impact of natural human genetic variation on health, and thus there are many opportunities to make progress.
Another challenge is to dispel negative perceptions of aging research. When asked what he thought of Google’s new “immortality” spin-off company, called Calico, Bill Gates said, “It seems pretty egocentric while we still have malaria and TB for rich people to fund things so they can live longer. It would be nice to live longer though, I admit.” Gates is obviously a thoughtful and caring person, and I totally understand his point of view. But it’s interesting to note that age is actually the biggest risk factor for dying from TB (tuberculosis) – because as the immune system weakens with age it allows for reactivation of latent TB infections. Even in the case of malaria, which indeed primarily kills children, who frequently die upon their first infection because they are not yet immune, aging remains a big risk factor for dying from any subsequent infections. Another concern frequently voiced is the potential for overpopulation, but this is a danger raised by aging research no more than from improvements in human health made possible by things like safe drinking water and antibiotics, and I don’t think we would seriously wish we hadn’t made those advances. The bigger point is that the aging research community is not focused on immortality, but is rather aimed at using an understanding of aging to improve wellbeing. I think this is in line with what innovators in the fields of science, medicine, and government have always tried to do.
A third challenge is to address some of the hype surrounding things like “anti-aging” therapies. I know from interactions with friends and family members that people are remarkably willing to spend resources on special foods, supplements, and other types of regimens that are advertised to slow or reverse aging. In fact, Americans spend more money on these sorts of things than on the entire NIH budget! Mostly these therapies are unproven, and are even potentially harmful, and I think organizations like the IOA can help people understand what really is known, what’s plausible, and what’s more likely to be snake oil. On a more positive note, there really are some potential “anti-aging” therapies that have arisen from recent research, for example metformin, which is being studied in a clinical trial. It will take time and effort to see if any of these therapies prove worthwhile for broadly protecting people from age-related diseases, but the only way to know is to do the work.
Q: You’ve received two separate IOA Pilot Awards as a Co-Principal Investigator (Co-PI) in Fiscal Years 2015 and 2018. How has this pilot program helped to share or guide your career as a researcher?
A: My co-PIs and I are very grateful for the support we’ve received from the IOA pilot grant program. This program is one of the most impactful functions of the IOA, because it helps provide seed money to explore high risk/high reward avenues of investigation, which if successful can be turned into more substantial support from outside sources. For example Chris Lengner (at the Penn Vet School) and I received an IOA pilot in 2015 to study the possibility of treating the rare disease dyskeratosis congenita using a novel approach to improved telomere maintenance. Things went well, and we have obtained NIH funding to continue our work, which we believe has implications for the treatment of not only dyskeratosis congenita but also certain age-related diseases found in the broader population, e.g. pulmonary fibrosis. With a new IOA pilot, Dimitri Monos (at CHOP) and I are investigating connections between Alzheimer’s disease and a part of the human genome called the major histocompatibility complex, which plays important roles in the immune system. We’re excited to see where these studies lead us.