Cerebrovascular Disease and Alzheimer’s: A lecture by IOA Visiting Scholar, Richard Mayeux, MD, MSc

Screen Shot 2017-12-13 at 1.55.13 PMOn Thursday, November 30, 2017, the University of Pennsylvania’s Institute on Aging (IOA) hosted their last Visiting Scholars Series lecture for the 2017 season featuring Richard Mayeux, MD, MSc. Dr. Mayeux is currently the Gertrude H. Sergievsky Professor of Neurology, Psychiatry and Epidemiology in the Gertrude H. Sergievsky Center and Taub Institute for Research on Alzheimer’s Disease and the Aging Brain. In addition, he is also the Chair of the Department of Neurology at Columbia University, New York.

Dr. Mayeux’s talk highlighted his research on cerebrovascular disease and its link to late-onset Alzheimer’s disease (LOAD). As described in a 2016 JAMA Neurology publication, Dr. Mayeux and his colleagues conducted a study of 6,553 participants — 4,044 women and 2,509 men with a mean age of 77 years. Upon using generalized mixed logistic regression models to test the association of cardiovascular disease (CV) risk factors with late-onset Alzheimer’s, they found that “in familial and sporadic LOAD, a history of stroke was significantly associated with increased disease risk and mediated the association between selected CV risk factors and LOAD, which appears to be independent of the LOAD-related genetic background.”

Essentially, the findings support the idea that 1) cerebrovascular disease is prevalent in the aged, and 2) cerebrovascular disease may trigger Alzheimer’s disease in a genetically susceptible person. Currently, Dr. Mayeux is working on a new grant to further investigate his idea and to look into how to handle the fact that cerebrovascular disease contributes to the phenotype of Alzheimer’s disease.

To read Dr. Mayeux’s full 2016 publication, “Contributions of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Center,” click here.

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The 2017 Joseph A. Pignolo Award in Aging Research: Nathan Basisty, PhD

On Wednesday, November 29, 2017, the Institute on Aging hosted their annual Joseph A. Pignolo Award in Aging Research. This year’s speaker, Nathan Basisty, PhD, a postdoctoral research fellow at The Buck Institute for Research on Aging, received the award for his 2016 paper titled “Mitochondrial-targeted catalase is good for the old mouse proteome, but not for the young: ‘reverse’ antagonistic pleiotropy?” published in Aging Cell.

Dr. Basisty’s research focuses heavily on the role of protein homeostasis in aging. Protein homeostasis is the process by which a cell retains an equilibrium of proteins to maintain its proper functions. According to a 2013 publication in Nature, it is believed that “a cell’s failure to maintain proper protein homeostasis has a major role in ageing and age-related diseases” (Nature Reviews Molecular Cell Biology 14, 55-61 (2013) BH Toyama and MW Hetzer). Dr. Basisty and his team are also looking at the role of this process in longevity with several interventions intended to extend lifespan in mammals.

In terms of future research, Dr. Basisty plans on expanding his studies to focus on method development to improve how well proteins can be characterized in the cell as well as how we can characterize the way proteins are regulated — or “turnover” — in the cell.

Learn more in Dr. Basisty’s short video interview below:

Learn more about the Jospeh A. Pignolo Award in Aging Research here.

“Modeling Neurodegenerative Diseases,” CNDR’s 2017 Marian S. Ware Research Retreat

Screen Shot 2017-11-09 at 1.27.43 PMOn Thursday, October 19, 2017, Penn’s Center for Neurodegenerative Disease Research (CNDR) hosted its annual Marian S. Ware Research Retreat. This year’s topic was “Modeling Neurodegenerative Diseases” and featured a variety of expert speakers within the field.

“As is the tradition with CNDR retreats, every year we focus on a different aspect of neurodegenerative disease. This year, our theme was how to model the complexity of these conditions, for example at the molecular, cellular, and systems levels. The internal and external speakers provided a rich sampling of cutting-edge work being done on each of these areas,” said Kelvin Luk, PhD, Research Assistant Professor of Pathology and Laboratory Medicine and organizer of this year’s CNDR Retreat.

“Among the highlights were the trainee presentations, while we were treated to some spectacular methods for visualizing intact tissues and modeling how disease might be spreading across the central nervous system. Our keynote speaker also finished off by giving a glimpse of the disease process as it advances in living AD patients.

Overall, I think/hope it was enjoyed by all that were present. The feedback was very positive and we were able to bring together many members of the local (Penn and extramural) community from very diverse backgrounds.” – Kelvin Luk, PhD

In addition to the lectures, the day-long event also includes an annual poster session where scientists in all stages of their career, from Penn and beyond, can present their current and recent neurodegenerative-disease related research. The top three posters are selected by experienced judges and are awarded prizes. See this year’s poster winners below!

2017 Marian S. Ware Research Retreat Poster Winners

1st Prize:

Poster Title: “Genome-wide Co-translational Decay of Canonical mRNAs”
Authors: Fadia Ibrahim, Manolis Maragkakis, Panagiotis Alexiou, and Zissimos Mourelatos
Affiliation: University of Pennsylvania Perelman School of Medicine, Department of Pathology and Laboratory Medicine, Division of Neuropathology

2nd Prize:

Poster Title: “Amnestic and Non-Amnestic Phenotypes of Alzheimer’s Disease: An MRI-Based Phasing Analysis”
Authors: Fulvio Da Re1,2,3, Jeffery S Phillips1,4, Laynie Dratch1, Carlo Ferrarese3, David J. Irwin1,4, Corey T. McMillan1,4, Eddie Lee5, Leslie M Shaw5, John Q Trojanowski5, David A Wolk4,6, and Murray Grossman1,4
Affiliation: 1) Penn FTD Center, University of Pennsylvania, 2) PhD Program in Neuroscience, University of MilanoBicocca, Milan, Italy, 3) School of Medicine and Surgery, Milan Center for Neuroscience (NeuroMI), University of MilanoBicocca, Milan, Italy, 4) Perelman School of Medicine, University of Pennsylvania, 5) Center for Neurodegenerative Disease Research, University of Pennsylvania, 6) Penn Memory Center, University of Pennsylvania

3rd Prize:

Poster Title: “Tau and Synuclein: a Tojan horse in the making?”
Authors: Hannah J. Brown, Fares Bassil, Shankar Pattabhiraman, Bin Zhang, Dawn Riddle, John Q. Trojanowski, Virginia M.-Y. Lee
Affiliations: Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine

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Full list of 2017 CNDR Retreat Speakers:Screen Shot 2017-11-09 at 1.26.02 PM.

Learn more about CNDR here.

REACT! Study, Round 2, comes to a close

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The University of Pennsylvania’s Institute on Aging wrapped up their second round of the Rhythm Experience and Africana Culture Trial (REACT!) on Monday, October 9, 2017.

The trial concluded with a celebratory award ceremony which included readings, art presentations, and a dance performance by the study participants. Dara Meekins, REACT! Study Coordinator, kicked off the ceremony with a welcome speech describing the importance and impact of this clinical trial. “This study was developed to investigate a culturally important form of physical activity that could enhance the neurocognitive health and physical and emotional well-being of older African Americans,” explained Dara. “Prior studies have shown promising effects of physical activity, but REACT! specifically seeks to provide a fun, engaging, and broadly translatable platform for reducing the health disparities that currently exist for older African Americans.”

Not all clinical trials are as pleasant and many require a variety of unfavorable medical procedures or testing. “I think this study shows you that if you don’t want to be probed or prodded with needles, we can still use your help,” says Dara.

REACT!Group2_endingceremony

Lewis Reddick, REACT! education group participant, is a perfect example of the many ways this study is bettering the lives of older African Americans. “This program has let me know about things that I still can do that I thought I couldn’t, such as my reading and writing,” he explained. “I couldn’t write the way I used to, I couldn’t read the way I used to… and [this study] got me started again and it has inspired me to maybe even go back to school!”

Mr. Reddick also expressed his praise and appreciation for Dara and the rest of the REACT! team, including Samuel Gorka, study coordinator, as well as several student interns. “Everyone was kind and we had a great time!” he said. “I looked forward to everyday that I came!”

Below are some highlights from the REACT! Dance Group’s wonderful performance led by African Dance Instructor, Yattah Jones! Their performance is set to the sounds of African Conga drums and tells a story of celebration, life, vitality, harvest & rebirth through a fusion of Afro-Caribbean dance styles.

REACT! is an Alzheimer’s Association-funded research study being conducted at the University of Pennsylvania and the University of Pittsburgh (Pittsburgh).

Learn more about the REACT! Study here.

Meet F. Bradley Johnson, MD, PhD: New IOA Associate Director!

johnson-brad.11052The 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.

Read Dr. Johnson’s full bio here.

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.

Penn Medicine’s 6th Annual 5K for the IOA & Memory Mile Walk

It was a warm Fall morning on Sunday, September 24, 2017 as 371 runners and walkers and 70 volunteers gathered for Penn Medicine’s 6th Annual 5K for the IOA and Memory Mile Walk.

The fundraiser, which takes place throughout Penn Park and the University of Pennsylvania campus, raised a total of $49,260 this year for Alzheimer’s and aging-related disease research efforts at Penn’s Institute on Aging.

In addition to its usual run and walk, the event also included pre and post-race yoga sessions, entertainment provided by DeeJay007, and photobooth fun for the whole family. This year’s overall male winner, Alexis Tingan (pictured below, left), finished the race in 17 minutes and 35 seconds, with the overall female winner, Sara McCuaig (pictured below, right), not far behind him with a time of 19 minutes and 24 seconds.

To view the full list of race results, click here.

Last week, CBS Philly interviewed PJ Brennan, MD, Chief Medical Officer at Penn Medicine who created the event in memory of his father who lost his battle with Alzheimer’s disease. “I thought it would be a fun way to get my community here together and bring some attention to the work that the Institute on Aging does and raise some money for this novel research,” said Brennan during the interview.

To view more photos of the event, click here.

Advancing the Health of an Aging Population: Friends of the NIA (FoNIA) Briefing 2017

Screen Shot 2017-07-12 at 12.31.50 PMOn Friday, July 7, 2017, Friends of the National Institute on Aging (FoNIA) hosted its annual briefing on ‘Advancing the Health of an Aging Population.’ These briefings provide important updates on the groundbreaking research that is supported by the NIA to promote the health and well-being of older adults. While registration for this meeting is open to the public, it is most heavily attended by representatives of other aging-related organizations, advocacy groups, and staff of Senators and House Representatives.

In addition to a lecture by NIA Director, Richard J. Hodes, MD, and Deputy Director, Marie A. Bernard, MD, this year also featured a presentation by Penn Medicine’s David J. Irwin, MD, MSTR, assistant professor of Neurology at the University of Pennsylvania and clinical neurologist at the Penn FTD Center. Dr. Irwin’s presentation titled “Bringing the microscope to clinic: improving the diagnosis of Alzheimer’s disease and related disorders” discussed some of the current challenges of diagnosing Alzheimer’s and other neurodegenerative conditions and how researchers at Penn and beyond are working to overcome these challenges through a variety of studies. Dr. Irwin also stressed the vital role that NIA and other institutes at the National Institutes of Health (NIH) play in making this research possible.

 “As a junior investigator, this has been a very exciting time for me to start my career with a rapid advance in our understanding of the genetics and pathophysiology of AD and related conditions – these advances would not be possible without publicly-funded programs through the NIA, NINDS and other institutes at NIH,” said Dr. Irwin. “I am very enthusiastic and thankful to have the opportunity to help advocate for the mission of the NIA, as this directly leads to the improvement in the care of patients I treat with AD and related disorders.”

Full presentation slides:

Kathy Jedrziewski, PhD, Deputy Director of the Institute on Aging, is the current Chair of Friends of the NIA (FoNIA). For more information on FoNIA, click here

Full 2017 FoNIA Briefing Flyer