Beeson Annual Report - American Federation for Aging Research

Paul B. BeesonCareer Development AwardsIn Aging Research Program

2011 ReportFeaturing the 2009 Scholars

Sponsors

National Institute on Aging

National Institute of Mental Health

National Institute of NeurologicalDisorders and Stroke

The Atlantic Philanthropies

The John A. Hartford Foundation

The Starr Foundation

National Institutes of Health Office ofDietary Supplements

And an anonymous donor

Administered by


American Federation for Aging Research

The Paul B. BeesonCareer DevelopmentAwards in Aging ResearchProgram

About Paul B. Beeson, MD(1908-2005)

Dr. Paul B. Beeson, arenowned physician,researcher, and teacher, wasthe inspiration behind the cre-ation of the Paul B. BeesonCareer Development Awardsin Aging Research Program.It was his vision to increasethe number of physicians withthe combined clinical, aca-demic, and scientific expertiseto care for a growing olderpopulation.

At the time of his death, Dr.Beeson was professor emeri-tus of medicine at the

University of Washington. Although retired,he remained active in the field of agingresearch, attending meetings and advisingmany Beeson Scholars. In his long and distin-guished career, he profoundly influenced thecareer paths of many physician-scientists andwas stalwart in his concern for the care anddignity of patients.

To date, 170 physician-scientists throughoutthe United States and the Island of Irelandhave emerged as leaders in the field, chang-ing the landscape of geriatric medicine andaging research. They serve as a testament tohis enduring legacy, not only providing thebest possible care for older adults, but alsotaking on the charge to train the next genera-tion of leaders.

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The Paul B. Beeson CareerDevelopment Awards in AgingResearch Program, now in its 16thyear, has come to exemplify one ofthe most successful public-privatepartnerships in aging research,teaching, and clinical practice.

To be a Beeson Scholar is to join aprestigious group of emergingleaders who are improving the careof older adults and adding new

knowledge about age-related diseases and disorders.Their work is increasing our understanding of the basicmechanisms underlying age-related diseases anddisorders, opening the door for potential drug trialsand clinical interventions. Their work is changing thelandscape of how we treat the clinical and social needsof older adults, whether it is identifying how exerciseand depression affect long-term health and implementingnew tools to combat it, challenging long-heldassumptions that exclude older patients from clinicaltrials, or exposing the alarming rise of elder abuse.

Message from Stephanie LedermanExecutive Director, American Federation for Aging Research

Beeson Scholars are also influencing patient treatmentdecisions and their research findings are adding to thediscourse about healthcare reform, healthcare access,public health, and health policy.

The 2009 Scholars, whose work we are highlighting andcelebrating in this year’s report, are studying ways todevelop age- and disease-specific treatment protocols,identify new strategies to protect against neuro-degenerative diseases, and reduce the high incidenceof hospital-acquired infections in older adults. They arealso looking at seemingly unrelated conditions such asheart disease and its impact on falls and cognitivefunction.

We thank our sponsors for supporting such work andthat of the many other Scholars and we welcome newpartners to join us to ensure that more researchers canbenefit from all that is Beeson.

Stephanie Lederman

StephanieLederman

“TobeaBeesonScholaris to joinaprestigiousgroupofemerging leaders.”

Paul B. Beeson Career Development Awards In Aging Research Program2

As part of the first group of BeesonScholars, it has been very gratifyingto witness the success of the Beesonprogram and the leadership rolesBeeson Scholars have assumed inacademic medicine and agingresearch. This significant network oftop physician-researchers withdiverse and complementary interestshas advanced knowledge in a broadarea of scientific investigation — from

the molecular to the societal — that will impact thehealth and well-being of our nation’s unprecedentednumber of older adults.

Our Scholars do not work in a vacuum. They arecollaborating with their peers across multiple disciplinesand educating and mentoring the next generation ofleaders in geriatric medicine and aging research.

The program has remained resilient and strong despitethe enormous changes that have taken place during thelast two decades and the challenges affecting ourhealthcare system and the new funding environment.

It takes time and resources for junior faculty to establishindependent research programs while meeting clinicaland administrative responsibilities. Yet grant funding ismore limited and there is a great deal more competitionto obtain funding. These promising researchers arespending an ever increasing portion of their time seekingand writing grants, curtailing their ability to study,conduct research, and elicit new discoveries that will gofrom the lab to the clinic.

The strength of the Beeson award is that it providessignificant financial and career development support, thelatter through the annual meeting of present and formerBeeson Scholars and their mentors. This allows Scholarsto establish research platforms, initiate new researchprojects, and meet and interact with others who will notonly help advance their careers by providing a launchpad for obtaining long-term extramural funding but alsoadvance the field. An example of the success of theBeeson program— especially since this has become ajoint NIH-private foundation joint venture — is thatBeeson Scholars are able to convert their K08 or K23Beeson awards to R01 grants at a much higher rate thanother K award grantees. However, these are challengingtimes for the various funding agencies and I hope thisnovel and highly successful program will continue foryears to come.

I am encouraged by the enormous commitment andcontributions of the Beeson Scholars and the work of the2009 awardees that is already in progress. And I amhonored and pleased to introduce them.

Edward H. Koo

Letter from Edward H. Koo, MDChair of the Program Advisory Committee

Edward Koo

research and geriatric medicine. In 1999 The StarrFoundation joined the partnership and an anonymousdonor joined in 2004. With the addition of the NationalInstitute on Aging, also in 2004, and of more recentpartners the National Institute of Mental Health and theNational Institute of Neurological Disorders and Stroke, theBeeson program has benefited some 170 juniorinvestigators to date.

Beeson History

To understand the enormous influence of the Beesonprogram is to know its history. When it was created in 1994,the field of geriatric medicine and aging research was notone that many physicians and scientists were encouraged topursue. Medical school curricula did not put a greatemphasis on training the next generation of physicians tocare for what was going to be a burgeoning agingpopulation. And there were few leaders to mentor early-career clinicians and researchers.

A 1993 report from the Institute of Medicine (IOM)highlighting the need for more physicians trained ingeriatrics spurred the creation of what is now called thePaul B. Beeson Career Development Awards in AgingResearch Program. Starting in 1994 with funding from TheJohn A. Hartford Foundation, The Atlantic Philanthropies,and The Commonwealth Fund, the program has grown tobe one of the largest and most successful public-privatepartnerships supporting development of leaders in aging

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Beeson Scholars are learning about and taking a largerrole in advocacy and outreach efforts to inform andinfluence leaders, policymakers, and the public aboutthe need for more support of aging research.

4 Paul B. Beeson Career Development Awards In Aging Research Program

In addition, The Atlantic Philanthropies provided supportfrom 2007-2009 for an expansion of the program to theIsland of Ireland, bringing the benefits of the BeesonProgram to the Republic of Ireland and Northern Irelandand supporting the academic careers of 5 additional Scholars.

Two decades later in its 2008 report, Retooling for an AgingAmerica: Building the Health Care Workforce, the IOM onceagain sounded the alarm that the nation was woefullyunprepared to care for the growing aging population. Thedifference is that the age shift has arrived. The number ofolder adults — with multiple and complex needs — isgrowing faster than the number of physicians and otherhealthcare providers trained in geriatric medicine andgerontology. Approximately 37 million Americans are 65and older. By 2030, it will grow to more than 71 million,accounting for nearly 20% of the population.

Benefits of Beeson

The Beeson Award has helped drive interest in geriatricmedicine and aging research by attracting top physician-scientists who are not only expanding knowledge in thefield but who are in turn mentoring others. Many successfulcollaborations among Scholars from multiple disciplineshave resulted from the wealth of networking opportunitiesthe grant provides, from the annual meetings to the Beesonwebsite (www.beeson.org).

Most Beeson Scholars would attest to the tremendous valueof the annual meeting, which is a cornerstone of theprogram. For example, Dr. E. Wesley Ely, a critical carespecialist from Vanderbilt University Medical Center and Dr.Malaz Boustani, a geriatrician from Indiana UniversityCenter for Aging Research, first met at a Beeson annualmeeting and realized that they had a shared interest inpreventing delirium and its long-term effects, particularlydelirium that results from stays in the intensive care unit(ICU). Their work has resulted in new treatment modelsbeing put into practice in hospitals worldwide and thecreation of a new medical society — see page 5. Anotherexample of collaboration among Beeson Scholars is that ofDrs. Laura Dugan and Jeremy Walston. They developed aninflammation and cognition project which was funded and isshowing promising results in initial data development.

Taking on New Roles — Advocacy andOutreach

As the political climate is changing, there is a greater needto be heard. Beeson Scholars are learning about and takinga larger role in advocacy and outreach efforts to inform andinfluence leaders, policymakers, and the public about theneed for more support of aging research.

AFAR will establish an Outreach Fund which will provideresources to the Scholars for a range of activities to bringthe issues of aging and age-related diseases and conditionsto the forefront of their institutions, specialty associations,and beyond. For example, Scholars and alumni can requestfunds to establish or support an Aging Task Force/SpecialInterest Group, invite a visiting professor to come to their

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institution, or organize symposia with an aging focus atspecialty meetings and other societies, allowing them topresent their Beeson-supported research findings and otheractivities to increase the visibility of aging research.

“The Beeson Scholars are powerful, strong, and becomingincreasingly influential,” says Corinne Rieder, executivedirector of The John A. Hartford Foundation. “Theirpresence is widely felt in academic, clinical, and political

Scholars report that the following features of the BeesonProgram have been most helpful in advancing their careers:

• Flexible and generous funding with ample resources topursue a research program.

• 75% of a Scholar’s time is protected for research.

• An outstanding support system. Senior faculty membersserve as mentors and Scholars are matched withmembers of the Beeson Program Advisory Committee,some of the most talented leaders in geriatrics andaging research.

• Extensive networking opportunities through the Beesonannual meeting, an interdisciplinary conference forScholars, mentors, and leaders in the field.

• Exchange of information among current and formerScholars from many disciplines.

• Alumni participation. Many Scholars continue to attendannual meetings, assume leadership roles in theprogram, and become mentors to the next generation.

circles. They have helped build and promote the field ofaging research and geriatric medicine far beyond peerswho share common interests and goals. And they havecreated an excitement not just in the scientific communitybut the larger public.”

The Basics of Beeson

Each year, as many as ten clinically-trained researchers areawarded a Beeson grant of $600,000-$800,000, coveringthree to five years for protected time in aging-relatedresearch.

Selecting Scholars from the top medical schools andresearch institutions, the program invests in developingmedical faculty in order to expand the nation’s capacity totrain physicians in geriatric medicine and conduct researchon aging. The award is often life and career-changing. ManyBeeson Scholars go on to devote their careers to advancingprogress in the basic mechanisms of aging and effectiveprevention and management of illnesses, and serve as rolemodels for future generations of physicians.


What You Do in the ICU: Beeson ScholarsImprove Health for the Long-Term

Beeson Scholars are changing the practice of clinical care.One striking example is redefining the way intensive careunit (ICU) patients are treated in order to reduce seriousand long-term complications.

Traditional ICU treatments rely on heavy sedation, highdoses of pain medications, machine monitoring, andkeeping patients immobile. This seemingly compassionatecare is aimed at reducing pain and anxiety and speedingrecovery, but it also dramatically increases the incidence ofdelirium. ICU-acquired delirium can affect patients longafter they leave the hospital in the form of reduced brainfunction, which is often manifested as problems withmemory and executive function. ICU survivors also sufferfrom an intense loss of muscle mass and an increase in theincidence of depression and post-traumatic stress disorder.2001 Beeson Scholar E. Wesley Ely, MD, MPH, professor ofMedicine and Critical Care at Vanderbilt University MedicalCenter and associate director of Aging Research for theTennessee Valley Geriatric Research Education ClinicalCenter (GRECC), explains that whether they are young orold, patients who arrive at the ICU because ofcomplications from their primary conditions often leave withnewly acquired and tremendously debilitating cognitive andfunctional deficits.

Research led during the past decade by Dr. Ely and hismany colleagues at Vanderbilt University's ICU Delirium andCognitive Impairment Study Group (www.icudelirium.org)spurred the creation of a five step protocol to improve theassessment and outcomes of medical and surgical ICUpatients. Called the ABCDEs of Critical Care, this qualityimprovement program includes measuring spontaneousAwakening and Breathing trials, Coordination between ICUteam members, Delirium monitoring and management, andEarly mobility and exercise. This evidence-based approachushers in some dramatic changes in the culture of care thathad become standard during the past three decades. It isdesigned (and some elements have shown) to helpstandardize communication, improve interdisciplinarypatient care, reduce length of hospital stay and mortality,and improve long-term cognitive and functional outcomes.Approximately 40% of hospitals have incorporated somepart of the ABCDE protocol in their ICUs and the deliriumtool is now translated into more than 20 languages andused worldwide.

Overall, this change in the culture of the ICU, itsorganization, and focus on vulnerable older patients istaking time but making progress. There are well-documented and marked improvements in patients’physical, cognitive, mental, and long-term health but on alarge-scale basis, more studies and cohort data are needed.

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In a recent Vanderbilt randomized, controlled trial of theABC section of the protocol published in The Lancet,patients’ ICU and hospital stays were reduced by four daysand one-year survival rates improved by 15% (up to 65%from 50%) simply by cutting the amount of sedation in half.

“We are finding that both patients and their families are sorelieved that ICU teams are now focusing on the brain bothduring and after the ICU stay,” says Dr. Ely. In the past, weused our ‘beeps and buzzers’ to help patients survive, butnow we are paying close attention to the quality of survivaland we know that the brain is the most important organdetermining that quality.”

The ABCDE program is garnering a lot of attention outsideof the hospital. Recently, The Wall Street Journal featuredthe ABCDEs and the work of other researchers studying therole of delirium during and post-ICU. It has also become amajor focus of a national quality improvement effort led bythe Institute for Healthcare Improvement (IHI) to implementthe ABCDEs at hospitals across the country.

Other Beeson Scholars are adding to the knowledge thatcan help improve ICU and post-ICU care. A 2007 grant fromThe John A. Hartford Foundation allowed 1997 ScholarHelen Hoenig, MD, MPH, associate professor of medicine

at Duke University Medical Center, to collaborate with Dr.Ely on one of the first pilot studies in cognitive and physicalrehabilitation of ICU survivors in the home-care setting.They evaluated functional mobility and home safety, whichincluded exercises to improve physical impairment instrength, balance, and endurance, and cognitive training toimprove decision-making and daily functioning. After 12weeks, participants showed significant improvement inexecutive function and mobility.

Malaz Boustani, MD, MPH, a 2005 Beeson Scholar who isassociate professor of Medicine at the Indiana UniversityCenter for Aging Research and scientist at the RegenstriefInstitute, is leading a study to improve pharmacologicmanagement of critical care ICU patients. Manymedications commonly used in the ICU, such asbenzodiazepines, contribute to delirium. Dr. Boustani’sresearch seeks to create a multi-componentpharmacological intervention that would include human andcomputer-based decision support systems to reduce drug-induced adverse events.

In July 2011, Indiana University Medical Center will open apost-ICU survivor clinic. The Critical Care Recovery Centerwill closely track and assess patients’ cognitive andfunctional status at three-month intervals and developindividualized treatment protocols to improve rehabilitation.Vanderbilt University Medical Center will also open an ICUSurvivor Clinic in July.

Drs. Ely and Boustani realized that they had shared interestswhen they first met at an annual Beeson meeting. Alongwith 1999 Beeson Scholar Edward Marcantonio, MD,director of Research in the Division of General Medicineand Primary Care at Harvard Medical Center, they helpedfound the American Delirium Society,(http://www.americandeliriumsociety.org) a collaborativeinterdisciplinary effort designed to better understand thescience of delirium and its prevention, treatment, and long-term consequences.

Dr. Cynthia Boyd has always beendrawn to older and more complexpatients. During her internalmedicine residency program, shesays, “I went out on house calls witha geriatrics fellow and I realized veryquickly that this was for me. Irealized that I really loved olderpeople, that I loved their stories andthinking about their health in

context of their whole life and their history and theirrelationships to other people.”

At the same time, Dr. Boyd was intrigued by thechallenge of figuring out how to best medicallyintervene for these patients. “As these two thingsmelded together, I was really struck by what we knowabout evidence-based medicine and how poorly muchof it applies to people with multiple chronic conditions,particularly older people,” she says.

Early in her medical fellowship, she started a projectlooking at how well clinical practice guidelines forpeople with single diseases worked for older peoplewith multiple chronic conditions, or multi-morbidities.“What we found backed up my hypothesis, which isthat they didn’t apply very well,” she says. Only rarelydid the guidelines discuss how well the evidenceactually applied to older people with multiple chronicconditions or address the breadth of issues importantto them. “People would end up on these incrediblycomplicated regimens with many, many medicines, anda lot of visits to doctors and healthcare professionals.”

For her Beeson project, Dr. Boyd is aiming to improvethe lot of such patients by examining how doctorsdeliver their healthcare. “We want to make them feelbetter, we want to make them more functional, and wewant to make better decisions that will directly lead toimproved outcomes in a way that is patient-centeredand evidence-based,” she says.

In other words, the care should account for individuals’unique circumstances and consider variables like theirmedical conditions, social support, values, goals, and

healthcare preferences. To get at these personalaspects, Dr. Boyd and her team are collectinginformation from patients, their family members,caregivers, and physicians. With the brief assessment —essentially a short survey — busy clinical practicesmight be more able to identify those who should be onphysicians’ radar screens. The results of that assessmentcould then inform follow-up conversations.

Among older patients, for example, researchers havefound that adherence goes down for every medicineadded. How can clinicians measure that treatmentburden and use it in an appropriate way in decision-making? “It’s not just a simple matter of knowing whenwe’re asking patients to do too much,” Dr. Boyd says.For a patient feeling particularly burdened by atreatment regimen, the assessment could help identifypriorities or ways to overcome the stumbling blockspreventing adherence. And a thoughtful approach andan open discussion regarding how much benefit variousoptions really deliver could help patients decide whichrepresent the best way forward for them, making themmore active participants of their treatment plans.

The Beeson award, Dr. Boyd says, has granted her the“enormous privilege” of protected research time,something she considers essential for transitioning tobeing a leader and developing a full research program.And with “truly phenomenal” peer networking, she hasdeveloped ongoing collaborations with three otherBeeson scholars. “The other thing that I think is reallyamazing is what you learn on a national level frompeople who are the mentors and the more seniorresearchers,” she says. “It’s really an unparalleledopportunity to develop collaborations and getmentoring nationally in aging research, which I think isvery unique and wonderful.”

Once her assessment tool has been refined, she hopesto test its interventional utility in the clinic. Thisevidence-based approach could help fill in some criticalknowledge gaps about which approaches are mostlikely to help older and more complicated individuals.“It’s really a very exciting field because there’s so muchthat we don’t know,” Dr. Boyd says, “and it’s veryrelevant to so many patients.”

Treatment Burden in Older Adults with Diabetes and Multimorbidity

Cynthia M. Boyd, MD, MPHAssociate Professor of MedicineJohns Hopkins University School of Medicine

MENTORS:Cynthia Rand, PhDCharles Boult, MD, MPH, MBABruce Leff, MD

Boyd


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As the world’s aging populationrapidly increases, humans are livinglonger than ever before, with theWorld Health Organizationcalculating an unprecedentedglobal life expectancy of 68 yearsfor babies born today. Thatlongevity, however, comes amid adisturbing uptick in the prevalenceof Alzheimer’s disease among

seniors. A century after it was first described, thedisease is quickly reaching epidemic proportions, withno effective prevention or treatment options yet insight. “So very simply, the bottom line of my researchis to understand the disease process so that we candevelop strategies to prevent and treat the disease,”says Dr. Dena Dubal.

Dr. Dubal’s efforts are focused on a little-known factorcalled collagen VI, which exists beyond the confines ofbrain cells as something called an extracellular matrixprotein. “What we discovered is that it’s very highlyexpressed in the brains of Alzheimer’s disease patientsand in mouse models of Alzheimer’s disease,” shesays. “And so we sought to ask, ‘Why is this proteinthat lives outside the cells so highly expressed, why is itso abundant, and what is it doing in the disease?’” Sofar, the emerging story suggests that by producing theprotein, brain cells are protecting themselves againstAlzheimer’s-associated toxins. In particular, Dr. Dubaland her colleagues have found that collagen VI canbind to amyloid-beta — a toxin believed to play acritical role in Alzheimer’s disease — and effectivelykeep it from attacking neurons.

As part of her Beeson project, Dr. Dubal ischaracterizing the potential effects of collagen VI inmice, in mouse neurons grown under lab conditions,and in Alzheimer’s-impacted brain tissue taken fromhuman patients. The work spans everything frombiochemical and molecular investigations of thedisease pathway to studying impacts on behavior andcognition in mice treated with collagen VI. “Thehypothesis is that if we were to increase this factoreven further, we would see a protection against the

disease, and if we were to take away that factor, wewould see a worsening of the disease,” she says.

Dr. Dubal says her strong passion for aging researchgoes back to her days as an undergraduate student,when aging was a common theme bridging her studiesin medical anthropology and neurobiology. Asubsequent class on the physiology of aging, she says,had her on the edge of her seat and brought home the“urgent need for scientific discoveries to prevent thesedevastating dementias that affect people of allcultures.” At that point, she developed a strongcommitment to become a physician-scientist. Shebegan by working to identify protective strategiesagainst diseases of aging in the brain, and eventuallyspecialized in dementias as a clinician.

With all of her accomplishments, Dr. Dubal calls theBeeson Award one of her greatest to date. “It hasenabled me to really develop into an independentinvestigator,” she says. “It’s enabled me to spearheadburning questions to really begin a line of independentresearch in the field of aging and degeneration. It’sopened many, many doors in terms of scientificnetworking and career development.” In short, shesays, the award has been a seminal turning point in hercareer.

“I come into this award with a very strong backgroundin neurology, neuroscience, and aging. But to reallybecome an independent investigator and leader in thefield of Alzheimer’s disease, I needed some veryspecific training and mentoring expertise,” Dr. Dubalsays. The Beeson award has given her that opportunityto learn cutting-edge approaches and techniquesthrough her exposure to world-renowned experts.

The therapeutic potential of collagen VI, she notes, isstill unclear. “But as we understand what can protectthe brain against disease, we can begin to understandhow to increase those factors,” she says. “It openswide the possibilities of really promising targets forprevention and therapy.”

Collagen VI: Novel Mechanisms and Functions in Alzheimer’s Disease

Dena Bou Dubal, MD, PhDAssistant Professor of NeurologyUniversity of California, San Francisco Medical School

MENTOR:Lennart Mucke, MD

Dubal

An ill or dehydrated person whostands up too quickly in themorning may feel a temporary boutof dizziness. For many older adults,that sensation never goes awayuntil they sit down — or pass out —and Dr. Chie Wei Fan wants tounderstand why.

The physical act of going from alying to standing position causes apint of blood to flow from the chest

to the abdomen, dropping the blood pressure andspurring a compensatory increase in the heart rate.Patients with a condition known as orthostatichypotension, however, are deficient in their responseto this blood pressure drop, whether in a diminishedrise in the heart rate or in a decreased constriction ofthe veins in the abomen and lower limbs. The result isa temporary reduction in blood supply to the brainand an accompanying feeling of dizziness.

Prolonged dizziness and a higher risk of falling resultfrom the body’s autonomic failure, as it is called. Thephenomenon increases with age, and as studies areincreasingly suggesting, more ominous implicationsmay include lower mental function, higher risk ofcardiovascular disease, and greater odds of deathfrom all causes. “A poorer response of blood pressureto standing seems to be related to a lot of physicalfailings and maybe include cognitive failings — and itmay even be related to mood,” Dr. Fan says.

Standard blood pressure readings lack the sensitivityto detect rapid changes. For her Beeson project, Dr.Fan is using a more sophisticated tool known as aFinometer. “It’s able to measure blood pressure on abeat-to-beat basis, so every heartbeat will produce ablood pressure measurement,” she says. With theequipment, she and her colleagues can scrutinize howpatients respond to standing up from a lying downposition within five seconds.

Tellingly, the researchers have identified three mainresponses. In younger, healthy volunteers, a quickrecovery follows the initial drop in blood pressure. In

older people, however, Dr. Fan’s team found that therecovery is often delayed — a subtle but importantdifference missed by standard blood pressure tests.And for a patient with autonomic failure, commonlyseen in someone with Parkinson’s disease or diabetes,the blood pressure never returns to normal.

One Parkinson’s patient in particular triggered hercuriosity: a 62-year-old man who attended her clinicbecause of falls and blackouts. Every time he stoodup, his dizziness increased so much that he was forcedto sit down. While standing, his vision was blurred, hishearing muffled, and his breathing labored. Dr. Fanand her colleagues adjusted his medications andhelped him make some lifestyle changes to improvehis cardiovascular health, thereby improving his bloodpressure recovery enough so that he could take avacation to Spain.

His may be an extreme form of the condition, but Dr.Fan says the success story suggests many others alsomight be helped. By using more sophisticatedequipment, she says, “We may be able to detect earlychanges. And if we intervene then, perhaps you’ll stopthe person from progressing to significant autonomicfailure.”

Dr. Fan has been able to tap into The Irish LongitudinalStudy on Ageing (TILDA), a rich clinical database thatmay help her answer the larger question of whyincreasing age brings an associated delay in bloodpressure recovery. With beat-to-beat measurements,she may be able to chart the long-term healthtrajectory of TILDA patients who show an earlyimpairment in their lying-to-standing recovery period.

The Beeson award, she says, has raised the profile ofaging research both at her university and throughoutIreland, and the yearly conference has given her the rareopportunity to directly interact with the field’s worldleaders. As a result, Dr. Fan has been able to focus onsolving an increasingly important clinical mystery.

“It’s a fascinating area,” she says. “Finding thattreatment of low blood pressure can improvesomebody’s concentration or their mood or theirability to interact with people, and improve theirquality of life — it’s been very rewarding.”

Age-related Autonomic Dysfunction and its Impact on Cognition,Gait and Falls

Chie Wei Fan, MD, RCPISenior Research FellowTrinity College Dublin, Ireland

MENTOR:Rose Anne Kenny, MD

Fan


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Dr. Ronan Mullan has seen adisturbing phenomenon amongmany of his patients withrheumatoid arthritis, an autoimmunedisease marked by chronic jointinflammation. “Rheumatoid arthritispatients die younger than healthypeople in the population,” Dr.Mullan says,” and in large part thatseems to be due to an acceleration

in the rates of atherosclerosis in these patients.”

With a range of related maladies, he says, rheumatoidarthritis patients actually appear older. “Their musclesalmost waste away, much like an older person’s would.So it’s kind of accelerated aging, really.”

Doctors have long known that obese people are athigher risk for strokes and heart attacks. So arerheumatoid arthritis patients, but Dr. Mullan says thosewith a highly active form of the disease — marked bybadly inflamed joints — are more likely to besignificantly underweight. So why do some gauntrheumatoid arthritis patients suffer the same fate asoverweight people?

A common denominator, Dr. Mullan says, may be theactivity of an inflammation-linked protein produced bythe liver, known as serum amyloid A. Among rheumatoidarthritis patients, he has found, those with high levels ofthe protein are at greater risk of developing cardiaccomplications. Other studies suggest the protein isinvolved in primary atherosclerosis and linked toobesity-related cardiovascular disease.

For his patients, Dr. Mullan wants to understand howpro-inflammatory serum amyloid A may be tyingtogether these disease pathways — and indeed, couldbe a key player in a cardiovascular disease mechanismobserved in obesity, arthritis, and aging. Accumulatingresearch already suggests that among some obeseindividuals and rheumatoid arthritis patients alike, fat isactively broken down into harmful byproducts. “Part ofmy work is looking at fat tissue in rheumatoid patientsto see how it’s behaving, because it’s never really beenlooked at before,” he says. “There’s probably

Acute Phase Serum Amyloid-A (A-SAA) in Ageing, Arthritis andObesity - Potential Common Mechanism for Cardiovascular Disease

Ronan Mullan, MBChB, PhDSenior Lecturer in RheumatologyUniversity College Dublin

MENTOR:Douglas Veale, MD

Mullan

something in the tissue that under certaincircumstances can potentiate inflammation.”

Amid a challenging economic climate in Ireland, Dr.Mullan says, the Beeson Award has been highlybeneficial to his ongoing research. “I just wouldn’t havehad the same opportunities without it,” he says. “From aprofessional point of a view, it has raised my standingenormously in the university. You have instant recognitionthat you didn’t before.” At the annual meetings, he says,he’s been welcomed with open arms and exposed to anexciting range of aging research beyond theimmunology field. “I’ve had a great experience.”

For one arm of his Beeson-supported project, Dr.Mullan is collecting fat tissue from the inflamed joints ofrheumatoid arthritis patients and analyzing the rich stewof molecules linked to inflammation. By comparing thistissue to fat collected elsewhere from the patients’bodies and from other patients with a non-inflammatoryform of arthritis, he hopes to characterize the uniquetraits of rheumatoid arthritis-associated tissue. His teamcan grow the tissue samples in the lab and assess theeffects of deliberately blocking the activity of serumamyloid A or other inflammation-linked molecules.

For a second arm of the research, Dr. Mullan and histeam are compiling demographic information andcardiovascular risk profiles for rheumatoid arthritispatients. Simultaneously, they’re measuring the serumamyloid A levels and inflammatory disease activity in thepatients’ joints, as well as their total body percentage fatmass and lean body mass using a technique calledwhole body densitometry. Essentially, Dr. Mullan aims tocorrelate each patient’s clinical history, genetic profile,and behavioral risk factors for cardiovascular diseasewith lab tests providing objective evidence of the overallcardiovascular risk. The patients can then be followedover time to investigate links between rheumatoidarthritis and cardiovascular disease outcomes.

Eventually, Dr. Mullan hopes his work might helpscientists figure out how to neutralize the serumamyloid A protein or block a link in the pathway,thereby helping rheumatoid arthritis patients avoid apotentially deadly consequence of the disease.

For late-onset Alzheimer’s disease,the cast of genetic culpritscontributing to the condition maynumber in the dozens. Research byDr. Christiane Reitz, however,suggests that a family of five genesmay play a central role insusceptibility to the disease.

In Alzheimer’s, a normal nerve cellconstituent known as amyloid

precursor protein is chopped up and transformed into atoxic byproduct called beta-amyloid. Eventually, theseprotein fragments stick together and form telltale clumpsin patients’ brains. “The main reason that there’s notherapy is that we really don’t yet understand how thisaccumulation of proteins in the brain happens,” Dr. Reitzsays.

In 2007, she and her colleagues took a big step towardclarifying the disease pathway by showing that a geneknown as SORL1 inhibits a key enzyme from cutting upamyloid precursor protein into its destructive derivative.Curtailing the cleaving activity of this enzyme, calledgamma-secretase, allowed fewer toxic breakdownproducts to form instead.

In contrast, too little SORL1 boosted the secretaseenzyme’s activity, increased the levels of clump-pronebeta-amyloid fragments, and heightened the risk ofAlzheimer’s disease. Since then, Reitz and her lab haveidentified four related genes that all seem to behave thesame way. Her ongoing investigation into how thesegenes function, supported by the Beeson award, hascontributed more clues to the murky disease process.

Dr. Reitz is systematically asking the same questions foreach gene: “What happens if we really alter this gene inthe cell? Does it lead to the toxic form of amyloid beinggenerated less or more?”

So far, her research suggests that for SORL1 and its fourrelatives, lower-than-normal gene activity does indeedyield higher concentrations of Alzheimer’s-associatedprotein plaques. If her results hold up to further scrutiny,“then of course, all of those genes would be a target fortherapy,” Dr. Reitz says.

In medical school, Dr. Reitz instantly gravitated towardneurology, and subsequently obtained her PhD ingenetics so she could focus on better understanding thegenetic basis of Alzheimer’s and neurodegenerativediseases. “With the Beeson award, it gives you thepossibility to network with people who are from othertop universities and working on other aging-relateddiseases,” she says.

The rare opportunity to receive direct feedback fromleading experts has helped her refine her grantproposals and has highlighted potential connections withother researchers. “Scientifically, there’s a lot ofdevelopment and a lot of collaboration,” she says. “Butthen in addition, it’s the mentoring part which is just veryhelpful.”

To characterize the role of SORL1 and its relatives inAlzheimer’s, Dr. Reitz has pursued multiple strategies.Initially, her team collects DNA samples from and conductsneurological examinations of recruited volunteers to detectsigns of the disease. Using powerful assays, the researchersmeasure each gene’s relative activity in healthy volunteersand in Alzheimer’s patients, and identify genetic variantsthat may be affecting those levels.

Significant differences between the two patient populationscan be further investigated by tinkering with each gene’srelative activity in human nerve cells grown in Petri dishes.By artificially switching a gene on or off, the researchers canobserve the impact on the gamma-secretase enzyme andon the buildup of beta-amyloid plaques. Finally, Dr. Reitz isexamining whether these same genes are turned on atlower levels in cells from the donated brains of patients whodied of Alzheimer’s disease.

All the tests support the same emerging story: when fullyfunctional, these five genes seem to keep the secretaseenzyme in check, preventing it from cutting amyloidprecursor protein. Fewer amyloid-beta plaques result,which may translate to a reduced risk of Alzheimer’s.

“The next step for those five genes — and others,probably — is how do they interact and what is thepathway?” Dr. Reitz says. With her extensive training,budding collaborations, and encouraging results, she’swell on her way to finding out.

Mapping Causative Factors in the Sortilin-related Pathway inAlzheimer's Disease

Christiane Reitz, MD, PhDAssistant Professor of NeurologyColumbia University College of Physicians and Surgeons

MENTOR:Richard Mayeux, MD, MSc

Reitz


132011 Report

When she was diagnosed with early-stage breast cancer at the age of79, one of Mara Schonberg’sgrandmothers made the difficultdecision to not pursue radiationtherapy. Meanwhile, Dr. Schonberg’sother grandmother steadfastlyrefused to receive anothermammogram after she turned 87.Watching them grapple with their

respective choices, Dr. Schonberg was reminded howlittle information is available to help older womenthrough the decision-making process for breast cancerscreening and treatment.

Clinical data on the effectiveness of mammographyscreening has typically included only women youngerthan 75, leaving older women with little guidance.When Dr. Schonberg was a medical resident, thecommon default for doctors was to continuemammograms regardless of age, with no priordiscussion of whether they were truly warranted.“We’re not trained on how to have theseconversations,” Dr. Schonberg says. “Nor is there a lotof data on how to do it.”

Dr. Schonberg is hoping to help fill that void throughtwo related Beeson projects. One is aimed at betterunderstanding the psychological impact and decision-making process of older women as they considerbreast cancer screening and treatment options. For asecond project, Dr. Schonberg is developing anaccessible tool to help those women make informeddecisions based on their own values and preferences.

Overall, experts estimate that about two-fifths of breastcancers are over-diagnosed, meaning that the tumorswould never be clinically significant in a woman’slifetime. But Dr. Schonberg says that number is likelyhigher for older women who may have slow-growingcancers and multiple competing illnesses. “If thatbreast cancer is never going to show up and nevercause significant morbidity or mortality, then finding itmay not be a good thing for all women,” she says.

To hear from the women themselves, she is comparingthe experiences of two groups who received abnormalmammograms and were recommended for a breastbiopsy: those aged 75 and older and those aged 65 to74. For the observational study, Dr. Schonberg issurveying both groups after their initial mammogram andagain after 4 to 6 months to assess their decision-makingprocess, quality of life, and other markers of well-being.

Although her results are still preliminary, the datasuggest that women aged 75 and older are more likelyto feel that their physician made their treatment choicesfor them and to feel less satisfied. Because the olderwomen tend to rely on their primary care providers morethan younger women, Dr. Schonberg says one lesson isthat those physicians should be better informed aboutthe intricacies of breast cancer treatment.

For her related project, Dr. Schonberg is developing adecision aid to help older women decide whether tocontinue receiving mammograms. To create theaccessible pamphlet, she interviewed experts in fieldsranging from geriatrics and oncology to epidemiologyand communications. Using visual cues, the pamphletexplains the average outcome of women who do or donot continue with breast cancer screening, and includes ascored questionnaire that estimates overall risk of death.Women who score higher have a greater overall risk ofdeath, and are less likely to benefit from mammographyscreening. Most importantly, the tool is designed to helpthem think about what they value most.

Dr. Schonberg is testing the tool in a primary care-based clinic to see whether it improves older women’sknowledge about the pros and cons of screening andwhether they consider it useful. She hopes that withbalanced information about options and outcomes andan approach that considers patients’ personal values,women will become more active participants indiscussing the best course of action with their doctorsand their loved ones.

Benefits and Burdens of Screening Oldest-old Women:The Case of Mammography

Mara Schonberg, MDAssistant Professor of MedicineBeth Israel Deaconess Medical Center/Harvard Medical School

Schonberg

MENTORS:Edward Marcantonio, MDRebecca Silliman, MD, PhDEllen McCarthy, PhD, MPH


With more than half of all kidneydialysis patients now over the age of65, doctors are seeing an increasingnumber of older candidates forkidney transplants. Yet most studiesof kidney transplant outcomes haveall but excluded this subpopulation.Older adults may have cognitiveissues and multiple chronicconditions, further complicating the

task of predicting who may do best after a transplant.

Dr. Dorry Segev, was among the doctors confronted bya lack of data and struggling with the question ofwhether certain patients were good transplantcandidates. “I saw some older adults do fantasticallywell after kidney transplants, and I saw some olderadults do quite poorly,” Dr. Segev says. “It wasfrustrating to me to not have been able to predictthose outcomes.”

After talking with geriatricians, he realized that betterpredictions would come only with a fuller understandingof the geriatric-specific issues faced by older patients.His Beeson award, Dr. Segev says, has let him focus on achallenging aspect of his field with major implicationsfor assisting individual decision-making and informingpolicy discussions on how donated organs should beallocated to older transplant candidates.

“The first goal was to try to figure out, using a largenational database, who are the appropriate oldercandidates for transplantation?” Dr. Segev says. Secondly,he wondered, how many of those predicted to be goodcandidates actually have access to transplantation?

“Under the hypothesis that we will find somediscrepancy between medical appropriateness andaccess to transplantation, then the question is, ‘Whatare the barriers to getting appropriate older adultslisted for transplants?’” he says. That question mayhave been less urgent 10 to 15 years ago, when olderpatients often didn’t fare well after receiving a donatedkidney. But better immunosuppression medication andmore clinical experience with older patients havemarkedly improved post-transplant survival for many.

To help with the predictive modeling, Dr. Segev tappedinto a rich database of nearly 7,000 older patientslinked to the Organ Procurement TransplantationNetwork. He and his collaborators have used advancedcomputer modeling techniques that take into accountthe varying interactions that can occur among apatient’s multiple chronic conditions. “We’re able tocategorize people by how good of a candidate theywould have been for a transplant,” he says, “and thenwe can go back to the whole dialysis population andsay, ‘What percentage of the good candidates actuallyhad access and what percentage did not have access?’”

Preliminary results have pointed to some eye-openingfindings. The top tier of kidney transplant candidatesover the age of 65, for example, collectively have a 90%chance of surviving at least three years after receiving akidney transplant. But Dr. Segev’s initial analysis showsthat fewer than 25% of these “excellent” candidateshave had access to one.

His work also has suggested a host of misconceptions.People who are less likely to pursue a transplant, forexample, are more likely to think they will do better thanpredicted on dialysis. Conversely, they’re more likely tothink a transplant will be riskier than predicted for them.Older patients say they don’t want to burden their familymembers or society, and have more doubts aboutwhether they could handle additional medications.

The Beeson award has allowed Dr. Segev to receiveformal training in geriatric issues and to create anetwork of geriatrics colleagues and mentors who havehelped him understand how those issues apply to hisown research. “Since I got my Beeson award, I’vereceived a PhD in clinical investigation, and I waspromoted to associate professor,” he says. “With theprotected time that it’s given me, it’s really opened forme an opportunity to grow significantly in my career.”

His ultimate goal, he says, is to ease the delicate processof determining whether a patient might benefit from akidney transplant. “If we can be more objective aboutthis,” he says, “then it would help people understandthat they may be good candidates and encourage themto seek out the transplant that would help them.”

Access to Kidney Transplantation in Elderly Patients

Dorry Segev, MD, PhDAssociate Professor of Surgery and EpidemiologyJohns Hopkins University School of Medicine

Segev

MENTORS:Robert Montgomery, MD, DPhilJeremy Walston, MD

152011 Report

A particularly cruel aspect ofAlzheimer’s disease is the slowerosion of memory and thinkingabilities. By the time patients maketheir first worried trip to the doctor,changes in the brain may havebeen brewing for a decade. Thegradual deterioration haspresented a challenge forresearchers who have little else to

help gauge the potential of candidate therapiesduring expensive clinical trials. “Right now, our clinicaltrials are stretching out to 18 months or two years tobe able to see if we’re making a difference,” says Dr.Edmond Teng.

Scientists have identified a few biological markers thatmay indicate early signs of the disease in a patient’scerebrospinal fluid — and potentially in the blood. Dr.Teng is asking whether researchers also can detectfurther changes in these markers that could be used as aproxy for disease progression. If so, he says, interventionsthat prevent or slow the disease might yield effects onthe biomarkers that appear long before changes in moretraditional measures of patient behavior.

“Even though it might take us 18 months to see adifference in memory and thinking, if we could see adifference within two or three months or sooner inblood or spinal fluid, we’d at least know we were on theright track,” Dr. Teng says. “We could identifytreatments that seem to be working earlier, and identifypatients who seem to respond to those treatmentsearlier as well.” One difficulty, though, is knowingwhether changes in biological markers really reflectchanges in disease severity. To address that uncertainty,he is studying laboratory rats that have been modifiedwith an introduced genetic mutation that leads toAlzheimer’s-related symptoms relatively quickly.

As part of his Beeson project, Dr. Teng is examining twomarkers in the rats’ cerebrospinal fluid that candistinguish between those that have Alzheimer’s andthose that don’t. For these disease-linked proteins,

amyloid-beta and tau, he is testing the ability of each totrack the improvements in memory and cognition thatresearchers have seen in treated animals. If a candidateintervention has a clinical effect in rats and alsosignificantly changes the levels of tau or beta-amyloidin the animal’s cerebrospinal fluid, researchers might beencouraged to test the same strategy in humans. “So itwould help make sure we could prioritize thetreatments that are most promising,” he says.

Dr. Teng became fascinated with memory during apsychology course in college, when he heard the storyof a famous patient named H.M. To control H.M.’sepileptic seizures, doctors removed the majority of astructure called the hippocampus from both sides ofhis brain. The operation worked, but H.M. was leftwith severe long-term memory problems. In graduateschool, Dr. Teng studied the memory-robbing impactsof hippocampal damage in monkeys and humans.Later, in medical school, he saw patients whosememories had likewise been stolen — this time byAlzheimer’s disease. With two family membersafflicted by the incurable disease, “it really strikes thatpersonal chord with me,” he says.

With the crucial support of the Beeson Award, Dr. Tenghas been applying his research knowledge to helpaddress a clinical epidemic that is expected to affect anestimated 16 million Americans by 2050. “The BeesonAward has been totally awesome,” he says, citing theprogram’s emphasis on mentorship and career support.At the annual meeting, he says, “you’re getting a lot offeedback from your peers but also feedback from moresenior members on a much more personal level thanyou might get at the bigger scientific meetings.”

Although he had secured some smaller grants duringhis medical fellowship, Dr. Teng was faced with makingthe career jump from being a trainee to running hisown lab. “And if I hadn’t gotten the Beeson Award Iprobably wouldn’t have been able to make thatjump,” he says. “So the award has been, I think,absolutely essential for me being able to continue topursue a career in academic medicine.”

Assessment of Biomarkers and Behavior in a Transgenic RatModel of AD

Edmond Teng, MD, PhDAssistant Professor of NeurologyUniversity of California, Los Angeles School of Medicine

MENTORS:Gregory Cole, PhDDouglas Galasko, MDClaude Wasterlain, MD

Teng

Urinary tract infections are by far themost common of all hospital-acquiredinfections, with an estimated inci-dence of more than 500,000 casesevery year. Researchers have blamedabout 80 percent of these infectionson the use of a urinary catheter, andDr. Heidi Wald is training a spotlighton the avoidable harm that such infec-tions can inflict on older patients.

“My timing is lucky because there’s a big focus nationwideat this point in time on hospital-acquired conditions, andspecifically hospital or healthcare-acquired infections,” Dr.Wald says. “Catheters have been used fairly cavalierly in allpatients, but in particular in elderly patients.”

Frail, older patients may suffer disproportionately fromcatheter-associated urinary tract infections, with studieslinking the infections to decreased mobility, a higher risk offalls, and and in some cases, even death. “Infections asso-ciated with catheters have previously been seen as part ofdoing business in hospitals,” she says. “And the paradigmhas really changed over the last couple of years in that thethought is, ‘You know, these are probably largely preventa-ble and we haven’t been doing everything that we can toprevent this additional harm to patients.’”

With the support of the Beeson Award, Dr. Wald is devel-oping a new method to reduce these infections through acollaboration with 20 hospitals enrolled in the NICHE(Nurses Improving the Care of Health System Elders)Program. One aim of the project is to test an automatedsurveillance system that helps hospitals track how they useurinary catheters and how often such use leads to infec-tions among their patients.

In return for compiling and sending data collectedthrough the surveillance system, each participating hospi-tal receives a report and either an immediate or delayedinterventional strategy in the form of education and feed-back. Dr. Wald can then assess whether early interventionhelps hospitals improve patient care. If the system proves

reliable, it could be distributed more widely to help hospi-tals reduce the infections.

Although Dr. Wald is applying a technical solution to theproblem, she says the project has broad implications.“Obviously, the main goal is to improve patient outcomesby reducing catheter use and urinary tract infections,” shesays. But by advancing the knowledge of electronic sur-veillance and how it can be used, her approach also mighthelp lower other hospitalization-associated risks, such aspressure ulcers (sometimes known as bedsores).

An automated surveillance system, Dr. Wald says, can freehospitals —many of them already short on personnel —from the time-intensive task of manually tracking catheteruse and associated urinary tract infections. By informinghospitals how often catheters are really used, and oftenoverused, she hopes the systemmight encourage staff torely on them less and in so doing reduce the risk of infec-tion.

An influential 1999 Institute of Medicine report on the highrate of medical errors spurred her interest in patient safety,and led to a new career trajectory that began with fellow-ships in geriatric medicine and primary care research.Eventually, Dr. Wald says, she saw a natural synergybetween the patient safety movement and the core valuesof geriatric medicine. Based on her clinical experience, shestarted focusing on urinary tract infections as a form ofpreventable harm. The Beeson award, Dr. Wald says, hasgiven her the welcome luxury of protected time to con-tinue working on her research and career development. “Itreally provides me with a lot of independence and flexibil-ity that I would not have otherwise had,” she says.

Once the issue of patient safety and hospital-acquiredinfections burst onto the national scene as a major pointof discussion in the larger debate over healthcare quality,“all of a sudden, people started to really understand whatI was doing,” Dr. Wald says. Now, hospitals and patientsaround the country stand to benefit from her expertise.

Reducing Urinary Tract Infections in the Hospitalized Older Patient

Heidi L. Wald, MD, MSPHAssociate Professor of MedicineUniversity of Colorado Denver

MENTORS:Andrew Kramer, MDElizabeth Capezuti, PhD, RNPeter Lindenauer, MD, MSc

Wald


172011 Report

Every few months, Dr. JonathanWanagat hears one of his patientstalk about the difficulties of gettingold. As a geriatrician, Dr. Wanagathas learned to ask an important butoften neglected follow-up question:What challenges are you facing?

“The vast majority of the time, theanswer to that question, regardless oftheir medical problems or their

societal or economic background, has been that theycan’t do what they did when they were younger,” hesays. Maintaining mobility and the ability to liveindependently are two major concerns among agingseniors, and Dr. Wanagat says an underappreciatedcondition may have an enormous role in underminingboth. “The impact I see in clinic every week is thatindividuals primarily lose their independence through avariety of mechanisms — weakness, falls, gait or balanceproblems, changes in metabolism — because they’relosing their muscle mass.”

This age-associated muscle loss, or sarcopenia, seldomappears on the medical charts listing a patient’s primaryproblems. Dr. Wanagat, however, believes thatunderstanding the mechanism underlying thisprogressive wasting away of muscle cells could be keyto preventing or at least delaying a major source ofdisability among older Americans.

For his Beeson project, he is focusing on the potentialrole of the cell’s energy factories, or mitochondria, in age-related sarcopenia. Mitochondria contain their own DNA,which can acquire sporadic mutations throughout theaging process. Mutations in the mitochondria may spreadwithin each thread-like muscle cell, or muscle fiber, killingoff the cell and gradually winnowing away the musclemass. “In that model, one can envision different points ofintervention that might either prevent the mutation,prevent the spread of a mutation or prevent the negativeoutcome of that mutation, namely, the fiber being lostfrom the population,” Dr. Wanagat says.

Using genetically modified mice, he is testing thehypothesis that halting an early step, a DNA mutation in

the mitochondria, may shield older animals from musclefiber loss. Dr. Wanagat’s lab mice contain a powerfulantioxidant enzyme that has been redirected to themitochondria to help protect against DNA-damagingmolecules. Other research found that these mice live 25percent longer than their unmodified peers, and Dr.Wanagat has determined that the animals also appearto be better safeguarded against sarcopenia. “We see alower mutation rate,” he says. “I find fewer of thesemitochondrial abnormalities in the muscles, and themuscles are a little bit larger in the oldest mice.”

Dr. Wanagat’s work represents an extension of hisgraduate research, which focused on mitochondrialaberrations and other abnormalities in the muscle cellsof aging rats. “The Beeson Award for me has beencritical mostly because I’m both a practicing geriatricianand a scientist,” he says. Without the protected timethat allows him to pursue his research, he says, movingforward in his investigation of mitochondria and muscleloss would have been extraordinarily difficult. The tight-knit group of Beeson Scholars and geriatricians alsoprovides a crucial support network. “I think there’s agreat camaraderie there,” he says. “Academic geriatricsin general is quite small, and the subset of thoseindividuals who do basic science is even smaller. So it’sgreat to have a way to be connected to those peoplefor resources or help with protocols or collaborations.”

With firmer evidence tying mitochondria to musclewasting, he says, researchers may gain a better handleon diagnosing sarcopenia, perhaps through telltalechanges in biological markers. More clarity also mighthelp clinicians devise interventions beyond exercise,which isn’t always realistic for patients who arerecovering from a fall or don’t feel comfortable walkingin unsafe neighborhoods. And mitochondria, he says,may present a better therapeutic target for antioxidantsthan giving patients general antioxidant supplementslike vitamin E, a strategy that has been largely unprovenin clinical trials.

“Hopefully, some of my work will uncover some of thesebasic mechanisms,” Dr. Wanagat says, “and give us targetsto start preventing the changes or slowing them down.”

Mitochondrial Genetics in Skeletal Muscle Aging

Jonathan Wanagat, MD, PhDAssistant Professor of MedicineUniversity of California, Los Angeles School of Medicine

MENTORS:David Reuben, MDSteven Clarke, PhD

Wanagat


2010

Jeffrey M. Caterino, MDAssistant Professor of Emergency Medicine and Internal MedicineThe Ohio State University College of Medicine

Anna Csiszar, MD, PhDAssistant Professor of Geriatric MedicineUniversity of Oklahoma Health Sciences Center

Leora I. Horwitz, MD, MHSAssistant Professor of MedicineYale University School of Medicine

Amy Jo Haavisto Kind, MD, PhDAssistant Professor of Geriatric MedicineUniversity of Wisconsin-Madison School of Medicine andPublic Health

J. Michael McWilliams, MD, PhDAssistant Professor of Health Care Policy and MedicineHarvard Medical School/Brigham and Women's Hospital

Timothy Miller, MD, PhDAssistant Professor in NeurologyWashington University School of Medicine

2009 Beeson Annual Meeting

Program Advisory Committee

Edward Koo, MD, ChairUniversity of California, San Diego School of Medicine

Christopher Callahan, MDIndiana University School of Medicine

Laura Dugan, MDUniversity of California, San Diego School of Medicine

Thomas Gill, MDYale University School of Medicine

Jean Kutner, MD, MSPHUniversity of Colorado Health Science Center

Mark Lachs, MDWeill Medical College of Cornell University

Richard Loeser, Jr, MDWake Forest University School of Medicine

Kristine Yaffe, MDUniversity of California, San Francisco School ofMedicine

Thomas Robinson, MDAssociate Professor of SurgeryUniversity of Colorado Denver

Stephen Thielke, MD, MSPH, MAAssistant Professor of Psychiatry and Behavioral SciencesUniversity of Washington

2009

Cynthia Boyd, MD, MPHAssociate Professor of MedicineJohns Hopkins University School of Medicine

Dena Dubal, MD, PhDAssistant Professor of NeurologyUniversity of California, San Francisco School of Medicine

Chie Wei Fan, MD, RCPI*Senior Research FellowTrinity College Dublin

Ronan H. Mullan, MBChB, PhD*Senior Lecturer in RheumatologyUniversity College Dublin

Christiane Reitz, MD, PhDAssistant Professor of NeurologyColumbia University College of Physicians and Surgeons

Beeson ScholarsTo learn more go to www.beeson.org

* Paul Beeson Career Development Awards in Aging Research Program for the Island of Ireland

192011 Report

Mara A. Schonberg, MD, MPHAssistant Professor of MedicineHarvard Medical School/Beth Israel Deaconess Medical Center

Dorry L. Segev, MD, PhDAssociate Professor of Surgery and EpidemiologyJohns Hopkins University School of Medicine

Edmond H. Teng, MD, PhDAssistant Professor of NeurologyUniversity of California, Los Angeles School of Medicine

Heidi L. Wald, MD, MSPHAssociate Professor of MedicineUniversity of Colorado Denver School of Medicine

Jonathan Wanagat, MD, PhDAssistant Professor of MedicineUniversity of California, Los Angeles School of Medicine

2008

Sarwat I. Chaudhry, MDAssistant Professor of MedicineYale University School of Medicine

Stephanie Cosentino, PhDAssistant Professor of NeuropsychologyColumbia University College of Physicians and Surgeons

XinQi Dong, MD, MPHAssociate Professor of Medicine, Nursing, and Behavioral ScienceRush University Medical Center

Susan E. Hardy, MD, PhDAssistant Professor of MedicineUniversity of Pittsburgh School of Medicine

Paul B. Rosenberg, MDAssistant Professor of Psychiatry and Behavioral SciencesJohns Hopkins University School of Medicine

Joseph S. Ross, MD, MHSAssistant Professor of MedicineYale University School of Medicine

Steven J. Russell, MD, PhDInstructor in MedicineHarvard Medical School/Joslin Diabetes Center

Arthur A. Simen, MD, PhDAssistant Professor of PsychiatryYale University School of Medicine

Farzaneh A. Sorond, MD, PhDAssistant Professor of NeurologyHarvard Medical School/Brigham & Women’s Hospital

Michael A. Steinman, MDAssistant Professor of Medicine in ResidenceUniversity of California, San Francisco School of Medicine

Stephen A. Todd, MD, MRCP*Senior Clinical Research FellowQueen’s University of Belfast

Douglas B. White, MD, MASAssociate Professor of MedicineUniversity of Pittsburgh Medical Center

Heather E. Whitson, MD, MHSAssistant Professor of Medicine (Geriatrics) and OphthalmologyDuke University Medical Center

2007

Randall J. Bateman, MDAssociate Professor of NeurologyWashington University School of Medicine

Julie P.W. Bynum, MD, MPHAssociate Professor of Medicine and Community Family MedicineDartmouth Medical School

Sascha Dublin, MD, PhDAssistant Scientific InvestigatorUniversity of Washington School of Medicine

Roee Holtzer, PhDAssociate Professor of PsychologyAlbert Einstein College of Medicine

Angela L. Jefferson, PhDAssociate Professor of NeurologyBoston University School of Medicine

Kimberly S. Johnson, MDAssistant Professor of MedicineDuke University Medical Center

Kejal Kantarci, MD, MScAssociate Professor of RadiologyMayo Clinic College of Medicine, Rochester

Patricia M. Kearney, MBBChBAO, PhD, MPH*Senior Lecturer in EpidemiologyUniversity College Cork, Ireland

Bernadette McGuinness, MD, MRCP*Senior Lecturer/Consultant GeriatricianSchool of Medicine, National University of Ireland Galway

Nicolas Musi, MDAssociate Professor of MedicineUniversity of Texas Health Science Center at San Antonio Schoolof Medicine

Neil A. Segal, MD, MSAssociate Professor of Orthopaedics & Rehabilitation, Radiology,and Epidemiology

The University of Iowa College of Medicine

Manjula Kurella Tamura, MD, MPHAssistant Professor of MedicineStanford University School of Medicine/Palo Alto VA Health CareSystem

Lihong Wang, MD, PhDAssistant Professor of PsychiatryDuke University Medical Center

* Paul Beeson Career Development Awards in Aging Research Program for the Island of Ireland

2006

Katrin F. Chua, MD, PhDAssistant Professor of MedicineStanford University School of Medicine

Margaret C. Fang, MD, MPHAssociate Professor of Medicine in ResidenceUniversity of California, San Francisco School of Medicine

Alex D. Federman, MD, MPHAssociate Professor of MedicineMount Sinai School of Medicine

Emily V.A. Finlayson, MD, MSAssistant Professor of SurgeryUniversity of California, San Francisco School of Medicine

Stacy M. Fischer, MDAssistant Professor of MedicineUniversity of Colorado Denver School of Medicine

Alfred L. Fisher, MD, PhDAssistant Professor of MedicineUniversity of Pittsburgh School of Medicine

Sean X. Leng, MD, PhDAssociate Professor of MedicineJohns Hopkins University School of Medicine

Ann M. O’Hare, MDAssociate Professor of MedicineUniversity of Washington School of Medicine

Caterina Rosano, MD, MPHAssociate Professor of EpidemiologyUniversity of Pittsburgh Graduate School of Public Health

Manish N. Shah, MD, MPHAssociate Professor of Emergency Medicine, Community andPreventative Medicine

University of Rochester School of Medicine and Dentistry

Consuelo H. Wilkins, MDAssociate Professor of Medicine and PsychiatryWashington University School of Medicine

2005

Liana G. Apostolova, MDAssociate Professor of NeurologyUniversity of California, Los Angeles School of Medicine

Malaz A. Boustani, MD, MPHAssociate Professor of MedicineIndiana University School of Medicine

Jennifer S. Brach, PhDAssociate Professor of Physical TherapyUniversity of Pittsburgh School of Health and RehabilitationSciences


Arleen F. Brown, MD, PhDAssociate Professor of General Internal Medicine and HumanServices Research

University of California, Los Angeles School of Medicine

Cynthia M. Carlsson, MD, MSAssociate Professor of MedicineUniversity of Wisconsin School of Medicine and Public Health

Daniel R. Goldstein, MDAssociate Professor of Medicine (Cardiology)Yale University School of Medicine

Wendolyn S. Gozansky, MD, MPHAssociate Professor of MedicineUniversity of Colorado Denver School of Medicine

Leanne Groban, MDAssociate Professor of AnesthesiologyWake Forest University School of Medicine

Arti Hurria, MDAssociate Professor of Medical OncologyCity of Hope

Pearl H. Seo, MD, MPHAssistant Professor of Clinical MedicineMiller School of Medicine at University of Miami

Dellara F. Terry, MD, MPHMedical DirectorDovetail Health

2004

Sandy Chang, MD, PhDAssociate Professor of Laboratory MedicineYale School of Medicine

Cathleen S. Colon-Emeric, MDAssociate Professor of MedicineDuke University Medical Center

William Dale, MD, PhDAssociate Professor of MedicineUniversity of Chicago School of Medicine

Lee E. Goldstein, MD, PhDAssociate Professor in Psychiatry, Neurology, Ophthalmology,Pathology & Laboratory Medicine, Biomedical Engineering,Electrical & Computer Engineering

Boston University School of Medicine, College of Engineering &Photonics Center

Cary P. Gross, MDAssociate Professor of MedicineYale School of Medicine

John J. Lehman, MDAssistant Professor of MedicineWashington University School of Medicine

2011 Report 21

Andrew P. Lieberman, MD, PhDAssociate Professor of PathologyUniversity of Michigan Medical School

Atul Malhotra, MDAssociate Professor of MedicineHarvard Medical School/Brigham and Women’s Hospital

Martin J. Sadowski, MD, PhDAssistant Professor of Neurology, Psychiatry, and PharmacologyNew York University School of Medicine

Catherine A. Sarkisian, MD, MSPHAssociate Professor of MedicineUniversity of California, Los Angeles School of Medicine

Clemens R. Scherzer, MDAssistant Professor of NeurologyHarvard Medical School/Brigham & Women’s Hospital

Lisa C. Silbert, MD, MCRAssistant Professor of NeurologyOregon Health and Sciences University

Joe Verghese, MDProfessor of NeurologyAlbert Einstein College of Medicine

2003

Meredith Hawkins, MDProfessor of MedicineAlbert Einstein College of Medicine

Michael C. Irizarry, MD, MPHInterim Head, WW EpidemiologyDirector and Therapy Area Lead, Neurosciences and InfectiousDisease Epidemiology

GlaxoSmithKline

Kenneth Langa, MD, PhDProfessor of Internal MedicineUniversity of Michigan Health System

Sarah H. Lisanby, MDProfessor and Chair, Department of Psychiatry & BehavioralSciences, and Department of Psychology & Neuroscience

Duke University Medical Center

Jack M. Parent, MDAssociate Professor of NeurologyUniversity of Michigan Health System

Henry L. Paulson, MD, PhDProfessor of NeurologyUniversity of Michigan Health System

Elizabeth A. Phelan, MD, MSAssociate Professor of Medicine/Gerontology and GeriatricMedicine and Adjunct Associate Professor of Health Services

University of Washington School of Public Health

Wendy S. Post, MD, MSAssociate Professor of Medicine and EpidemiologyJohns Hopkins University

Norman E. Sharpless, MDProfessor of Medicine and GeneticsUniversity of North Carolina at Chapel Hill, School of Medicine

Michael G. Shlipak, MD, MPHProfessor of Medicine, Epidemiology and BiostatisticsUniversity of California, San Francisco School of Medicine

Reisa A. Sperling, MD, MMScAssociate Professor of NeurologyHarvard Medical School/Brigham & Women’sHospital/Massachusetts General Hospital

2002

David J. Casarett, MDAssociate Professor of MedicineUniversity of Pennsylvania School of Medicine

James E. Galvin, MDProfessor of Neurology and PsychiatryNew York University School of Medicine

F. Brad Johnson, MD, PhDAssociate Professor of Pathology & Laboratory MedicineUniversity of Pennsylvania School of Medicine

Albert R. La Spada, MD, PhD, FACMGProfessor of Pediatrics, Cellular & Molecular Medicine,Neurosciences and Biological Sciences and Vice Chair andDivision Head of Genetics

University of California, San Diego School of Medicine

Michael T. Lin, MDAssociate Professor of Neurology & NeuroscienceWeill Medical College of Cornell University

Robert A. Marciniak, MD, PhDAssociate Professor of Medicine and Cell & Structural BiologyUniversity of Texas Health Science Center at San Antonio

Laura E. Niklason, MD, PhDProfessor of Anesthesiology & Biomedical EngineeringYale University School of Medicine

Michael A. Schwarzschild, MD, PhDAssociate Professor of NeurologyHarvard Medical School/Massachusetts General Hospital

Jürgen Unützer, MD, MPH, MAProfessor of Psychiatry and Behavioral SciencesUniversity of Washington Medical Center

2001

Asa Abeliovich, MD, PhDAssociate Professor of Pathology and NeurologyColumbia University College of Physicians & Surgeons

Katrin Andreasson, MDAssociate Professor of Neurology and Neurological SciencesStanford University School of Medicine

Eric A. Coleman, MD, MPHProfessor of Geriatric MedicineUniversity of Colorado Denver School of Medicine

Jay M. Edelberg, MD, PhDGroup Director - US MedicalBristol-Myers Squibb Company

E. Wesley Ely, MD, MPH, FCCPProfessor of MedicineVanderbilt University

Roger J. Hajjar, MDProfessor of MedicineMount Sinai School of Medicine

James A. Mastrianni, MD, PhDAssociate Professor of NeurologyUniversity of Chicago School of Medicine

Michael C. Naski, MD, PhDAssociate Professor of PathologyUniversity of Texas Health Science Center at San Antonio Schoolof Medicine

M. Carrington Reid, MD, PhDAssociate Professor of MedicineWeill Medical College of Cornell University

Mary Whooley, MDProfessor of Medicine, Epidemiology and BiostatisticsUniversity of California, San Francisco School of Medicine

Kristine Yaffe, MDProfessor of Psychiatry, Neurology, and Epidemiology andBiostatistics

University of California, San Francisco School of Medicine

2000

Brock Beamer, MDAssistant Professor of MedicineUniversity of Maryland, Baltimore School of Medicine

Gunnar K. Gouras, MDProfessor of NeuroscienceLund University, Sweden

Mary Beth Hamel, MD, MPHAssociate Professor in MedicineHarvard Medical School/Beth Israel Deaconess Medical Center

Paul B. Beeson Career Development Awards In Aging Research Program22

Joshua M. Hare, MDProfessor of MedicineMiller School of Medicine at University of Miami

Fuki M. Hisama, MDAssociate Professor of Medicine (Genetics) and NeurologyUniversity of Washington School of Medicine

Jason Karlawish, MDProfessor of Medicine and Medical EthicsUniversity of Pennsylvania School of Medicine

Jean S. Kutner, MD, MSPHProfessor of MedicineUniversity of Colorado Denver School of Medicine

Brett Lauring, MD, PhDProject Leader, Early Development Project & Pipeline LeadershipMerck Research Labs

Frank S. Lee, MD, PhDAssociate Professor of Pathology and Laboratory MedicineUniversity of Pennsylvania School of Medicine

R. Sean Morrison, MDProfessor of Palliative CareMount Sinai School of Medicine

Scott A. Small, MDProfessor in NeurologyColumbia University College of Physicians & Surgeons

1999

Kenneth E. Covinsky, MD, MPHProfessor of MedicineUniversity of California, San Francisco School of Medicine

Matthew P. Frosch, MD, PhDAssociate Professor of Pathology and Health Sciences &Technology

Harvard Medical School/Massachusetts General Hospital

Daniel T. LaskowitzAssociate Professor of Medicine (Neurology)Duke University Medical Center

Dale Leitman, MD, PhDAdjunct Professor of Nutritional Science and ToxicologyUniversity of California, Berkeley

Richard Z. Lin, MDProfessor of Medicine and Physiology & BiophysicsStony Brook University School of Medicine

David R. Lynch, MD, PhDAssociate Professor of NeurologyUniversity of Pennsylvania School of Medicine

Edward R. Marcantonio, MD, SMAssociate Professor of MedicineHarvard Medical School/Beth Israel Deaconess Medical Center

2011 Report 23

1997

Nir Barzilai, MDProfessor of Medicine and GeneticsAlbert Einstein College of Medicine

Michele Bellantoni, MDAssociate Professor of MedicineJohns Hopkins University School of Medicine

James R. Burke, MD, PhDAssociate Professor of MedicineDuke University Medical Center

Mark D’Esposito, MDProfessor of Neuroscience and PsychologyUniversity of California, Berkeley

Thomas M. Gill, MDProfessor of Medicine, Epidemiology & Investigative MedicineYale University School of Medicine

Bernard F. Godley, MD, PhDProfessor and Chair, Department of Ophthalmology andVisual Sciences

The University of Texas Medical Branch

Todd E. Golde, MD, PhDProfessor of NeuroscienceUniversity of Florida College of Medicine

Helen Hoenig, MD, MPHAssociate Professor of MedicineDuke University Medical Center

Elan D. Louis, MD, MScProfessor of Neurology and EpidemiologyColumbia University College of Physicians and Surgeons

Charles A. Thornton, MDProfessor of NeurologyUniversity of Rochester School of Medicine and Dentistry

1996

Christopher M. Callahan, MDProfessor of MedicineIndiana University School of Medicine

Robert W. Doms, MD, PhDProfessor of Pathology and Laboratory Medicine and Chair,Department of Microbiology

University of Pennsylvania School of Medicine

P. Murali Doraiswamy, MBBSProfessor of Psychiatry and MedicineDuke University Medical Center

Mitchell S. Nobler, MDAssociate Professor of Clinical PsychiatryNew York State Psychiatric Institute/Columbia University Collegeof Physicians & Surgeons

Anne Louise Oaklander, MD, PhDAssociate Professor of NeurologyHarvard Medical School/Massachusetts General Hospital

Thomas A. Rando, MD, PhDProfessor of NeurologyStanford University School of Medicine

1998

Helene Benveniste, MD, PhDProfessor of AnesthesiologyStony Brook University Medical Center

Laura L. Dugan, MDProfessor of MedicineUniversity of California, San Diego School of Medicine

Terri R. Fried, MDProfessor of MedicineYale University School of Medicine

Anne M. Kenny, MDProfessor of MedicineUniversity of Connecticut Health Center

Alison A. Moore, MD, MPHProfessor of Medicine and PsychiatryUniversity of California, Los Angeles School of Medicine

Thomas T. Perls, MD, MPHAssociate Professor of Medicine and GeriatricsBoston University School of Medicine

Eric D. Peterson, MD, MPHProfessor of MedicineDuke University Medical Center

R. Scott Turner, MD, PhDProfessor of NeurologyGeorgetown University Medical Center

Jeremy D. Walston, MDProfessor of MedicineJohns Hopkins University School of Medicine

Raymond Yung, MDProfessor of Internal MedicineUniversity of Michigan Medical School


Harlan M. Krumholz, MDProfessor of MedicineYale University School of Medicine

Makau Lee, MD, PhDDirector of Digestive DiseasesJackson Medical Clinic

Richard F. Loeser, Jr., MDProfessor of Internal MedicineWake Forest University School of Medicine

Karen M. Prestwood, MDFormer Associate Professor of MedicineUniversity of Connecticut Health Center

May J. Reed, MDAssociate Professor of MedicineUniversity of Washington School of Medicine

R. Glenn Smith, MD, PhDProfessor and Vice-Chairman of NeurologyUniversity of Texas Medical Branch

1995

Ashley I. Bush, MD, PhDProfessor of Pathology and Australia FellowMental Health Research Institute, University of Melbourne, Victoria,Australia

Ted M. Dawson, MD, PhDProfessor of Neurology and NeuroscienceJohns Hopkins University School of Medicine

David M. Holtzman, MDProfessor and Chairman, Department of NeurologyWashington University School of Medicine

Edward H. Koo, MDProfessor of NeurosciencesUniversity of California, San Diego School of Medicine

Mark Lachs, MD, MPHProfessor of MedicineWeill Medical College of Cornell University

Frank M. Longo, MD, PhDProfessor and Chairman, Department ofNeurology and Neurological Sciences

Stanford University School of Medicine

Richard A. Marottoli, MD, MPHAssociate Professor of MedicineYale University School of Medicine

Lina M. Obeid, MDProfessor of MedicineMedical University of South Carolina

Peter Reaven, MDProfessor of Clinical MedicineUniversity of Arizona School of Medicine

Alan R. Shuldiner, MDProfessor of MedicineUniversity of Maryland, Baltimore School of Medicine

All inquiries and correspondenceshould be directed to:

American Federation for Aging Research (AFAR)55 West 39th Street, 16th FloorNew York, NY 10018T: 212.703.9977F: 212.997.0330E: [email protected], www.beeson.org, &www.geriatricsrecruitment.org

Stephanie LedermanExecutive Director

Ashby AndrewsCommunications and Development Officer

Katherine Kelly AppleCommunications and Development Program Associate

Aimee CegelkaProgram Associate

Catherine CullarAdministrative Manager

Michelle ElliottAccounting Assistant

Hattie HermanProgram Officer

Nancy O’LearyDirector, Development

Jacalyn SchwartzDirector, Finance

Odette van der WillikDirector, Grant Programs

About the American Federationfor Aging Research (AFAR)

AFAR is a nonprofit organization whose missionis to support biomedical research on aging.It is devoted to creating the knowledge thatall of us need to live healthy, productive, andindependent lives. Since 1981, AFAR hasawarded approximately $132 million to morethan 2,800 talented scientists as part of itsbroad-based series of grant programs. Itswork has led to significant advances in ourunderstanding of aging processes, age-relateddiseases, and healthy aging practices. AFARcommunicates news of these innovationsthrough its organizational web site www.afar.org.

Additional writing supportprovided by:Bryn NelsonStacey Harris

We would like to thank the BeesonScholars for reviewing this reportfor scientific accuracy.

Sponsors:

National Institute on AgingNational Institute of Mental HealthNational Institute of NeurologicalDisorders and Stroke

The Atlantic PhilanthropiesThe John A. Hartford FoundationThe Starr FoundationNational Institutes of Health Officeof Dietary Supplements

And an anonymous donor

Administered by:


American Federation for AgingResearch

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Beeson Annual Report - American Federation for Aging Research

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