The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.
The site is secure.
The
https://
ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.
The 124th meeting of the National Advisory Council on Aging (NACA) was convened on Tuesday, January 27, 2015, at 3 p.m. in Building 45, Conference Room E1/E2, National Institutes of Health (NIH), Bethesda, MD. Richard J. Hodes, M.D., director, National Institute on Aging (NIA), presided.
In accordance with the provisions of Public Law 92–463, the meeting was closed to the public on Tuesday, January 27, from 3 to 5 p.m. for the review, discussion, and evaluation of grant applications in accordance with the provisions set forth in Sections 552(b)(c)(4) and 552(b)(c)(6), Title 5, U.S. Code and Section 10(d) of the Public Law 92–463.1The meeting was open to the public on Wednesday, January 28, from 8 a.m. to 1 p.m.
Council Participants:
Dr. Kimberly Acquaviva
Dr. Laura Carstensen
Dr. Ana M. Cuervo
Dr. Steven R. Cummings
Ms. Jennie C. Hansen
Dr. Kevin P. High
Dr. Bradley T. Hyman
Dr. Richard Mayeux (Attended by teleconference)
Dr. Charles P. Mouton
Dr. Thomas A. Rando
Dr. Jonathan S. Skinner
Dr. Reisa A. Sperling (Attended by teleconference)
Dr. Debra Bailey Whitman
Ex Officio Participants:
Dr. Richard M. Allman, Veterans Health Administration
Dr. Jane Tilly, Administration for Community Living
Absent Ex Officio Participants:
Dr. Kenneth G. Pugh, National Naval Medical Center
Mr. Edwin L. Walker, Administration on Aging
The Council Roster, which gives titles, affiliations, and terms of appointment, is appended to these minutes as attachment A.
Members of the Public Present:
Dr. Kathleen Abrahamson, Purdue University
Dr. Rozalyn Anderson, University of Wisconsin School of Medicine and Public Health
Mr. James Appleby, Gerontological Society of America
Dr. Johannes Haushofer, Princeton University
Dr. Howard Neil Hodis, University of Southern California
Dr. Perry Kirkham, Purdue University
Dr. Meghan McDonough, Purdue University
Dr. Frances McFarland Horne, Rose Li and Associates, Inc.
Dr. Richard Morimoto, Northwestern University
Dr. Shirley Rietdyk, Purdue University
REVIEW OF APPLICATIONS
This portion of the meeting was closed to the public, in accordance with the determination that it concerned matters exempt from mandatory disclosure under Sections 552(b)(c)(4) and 552(b)(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix).1
A total of 1,237 applications requesting $450,142,318 for all years underwent initial review. The Council recommended 712 awards for a total of $264,595,737 for all years. The actual funding of the awards recommended is determined by the availability of funds, percentile ranks, priority scores, and program relevance.
CALL TO ORDER
Dr. Hodes welcomed members to the open session of the 124th NACA meeting and called the meeting to order at 8 a.m. on Wednesday, January 28, 2015. Robin Barr, Ph.D., Council executive secretary, announced that the Honorable Sylvia Mathews Burwell, HHS secretary, would be speaking to the NIH director and staff at noon. To allow Council an opportunity to hear her remarks, Dr. Hodes shortened his report and other speakers agreed to present at an earlier time.
Director’s Status Report
Dr. Hodes reported that the latest appropriations omnibus legislation has provided greater stability, as NIH now has a set budget for the remainder of FY2015. This legislation provides a modest increase to all Institutes and Centers (ICs) and an additional $25 million to NIA primarily to support research on Alzheimer’s Disease (AD). Dr. Hodes reminded Council that the NIH budget was reduced in FY2013 as a result of the sequestration and that, despite increases in FY2014 and FY2015, the NIH budget continues to erode in terms of purchasing power.
Dr. Hodes noted other legislation requiring NIH to submit a bypass budget. With this legislation, the NIH director will propose a budget directly to Congress, referring particularly to AD research. In this proposal, the NIH director must indicate the level of research necessary to achieve the goals of the Alzheimer’s Disease Act and develop effective interventions by 2025. The President and HHS secretary can provide comments on the proposed budget but they cannot make changes to it. Dr. Hodes noted that Council also will have an opportunity to comment on the bypass budget.
Other areas of interest to Congress include the NIH Strategic Plan, support for younger investigators, the Common Fund, health economics, and prioritization of funding with respect to the balance between research and education. Dr. Hodes noted that Congressional language includes new rules regarding compensation for the provision of animal models. He also reported that more responsibility for conference approvals will reside with NIH, rather than the Department level.
Dr. Hodes closed his presentation by noting that, of the advances in science highlighted by Science for 2014, four were associated with NIA and/or NIH. He also reminded Council that the AD Research Planning Summit would be held February 9–10, 2015. In addition, planning for the White House Conference on Aging and the HHS Healthy Aging Summit is under way and NIA staffs are serving as liaisons.
The following new NIA staff members were introduced: Lisa Onken, Ph.D., who has joined the Division of Behavioral and Social Research (DBSR); Rasheda Parks, Ph.D., and Jaron Lockett, Ph.D., who have joined the Office of Planning, Analysis, and Evaluation; and Austin Yang, Ph.D., who has joined the Division of Neuroscience (DN). David Finkelstein, Ph.D., has retired from the Division of Aging Biology (DAB).
Future Meeting Dates
May 12–13, 2015 (Tuesday and Wednesday, Natcher Building)
September 16–17, 2015 (Wednesday and Thursday, Building 31)
January 19–20, 2016 (Tuesday and Wednesday, Building 31)
Consideration of Minutes of the Last Meeting
The minutes of the September 2014 meeting were considered. A motion was made, seconded, and passed unanimously to approve the minutes.
REPORT: TASK FORCE ON MINORITY AGING RESEARCH
Ana Cuervo, Ph.D., summarized three presentations that the Task Force had heard on the previous day. The first, given by Pamela Thornton, Ph.D., focused on efforts to enhance diversity in the NIH-funded workforce. After reminding the Task Force of the 2011 report highlighting racial disparities in R01 awards, Dr. Thornton described three Common Fund-supported initiatives aimed at the workforce pipeline, which narrows at each stage of training. The Building Infrastructure Leading to Diversity (BUILD) program supports new and transformative approaches toward training and mentoring to retain researchers from underrepresented minority groups. The National Research Mentoring Network (NRMN), which comprises five core initiatives and five regional hubs across the nation, plans and coordinates mentoring activities, for example to “train the trainer.” The Coordination and Evaluation Center (CEC) continuously reviews BUILD and NRMN to identify programs and interventions that have the most impact. Dr. Cuervo noted that aging research and NIA-supported centers offer several training opportunities and she encouraged NIA to communicate with the CEC.
The second presentation, given by Salman Tajuddin, Ph.D., was part of a series of presentations spotlighting exciting projects in health disparities research. Dr. Tajuddin’s presentation described his work on genetic determinants that predispose African American individuals to cardiovascular disease, particularly atherosclerosis. Taking advantage of the Healthy Aging in Neighborhoods of Diversity Across the Lifespan (HANDLS) study, Dr. Tajuddin has identified three single nucleotide polymorphisms associated with atherosclerosis. Functional studies are underway.
The third presentation, led by Carl Hill, Ph.D., involved a moderated discussion on concept clearance in health disparities research. In its last review of NIA research in minority aging and health disparities, the Task Force had recommended the adoption of an integrative, conceptual framework across the NIA. This framework identified stress as a common theme among NIA research topics. Stress also had emerged as a common theme as Dr. Hill worked with the NIA Divisions to develop ideas for addressing health disparities. Dr. Hill presented a model in which each Division creates its own initiatives around stress and another in which NIA identifies applications that would engage two or more Divisions. Dr. Cuervo reported that, during the previous day’s discussion, the Task Force highlighted resilience as a related commonality and expressed enthusiasm for the second model. Dr. Hill will present this concept at the next NACA meeting.
Inclusion Report
The Council reviewed the inclusion report for 2013–2014. Dr. Barr noted that the official report states that in 2014, 38% of trial participants were Asian. Dr. Barr reminded Council that these numbers were skewed by large epidemiological and demographic studies in China, Indonesia, and Bangladesh, which account for approximately 60% of Asian participants in NIA-supported protocols. Dr. Barr noted that the reporting system has changed as of 2015 to allow NIA to integrate overall data files with its own data systems. This will allow NIA to parse out the true clinical research and provide a more accurate reflection of how race and ethnicity are distributed. During the previous day’s discussion, the Task Force suggested that Dr. Barr’s remarks about distortions in the data be put into text, which will be done.
A motion to approve the inclusion report was forwarded and seconded. The motion passed unanimously.
NACA PHYSICIAN-SCIENTIST WORKING GROUP
NIA staff have expressed concern about the marked declines in the number of K award applications submitted by M.D.s and M.D./Ph.D.s. At the same time, Council members have expressed concern that the K award may be losing relevance for physician-scientists because average salaries have outpaced those supported by the award, institutions are unable to fill the gap, and institutions are unable to support research time. Council members also have questioned whether other mechanisms, such as the Clinical and Translational Science Awards, might be better mechanisms for training physician-scientists. In response to these concerns, NIA has established a working group to determine why the number of K award applications have fallen, how well K awards might “jump start” research careers, and how to increase the relevance of these awards for physician-scientists.
Kevin High, M.D., chair of the NIA Working Group, provided an update of the group’s activities to date, including a recent meeting with Sherry Mills, M.D., director of the NIH Office of Extramural Research and co-chair of the NIH Physician-Scientist Workforce Working Group. On the basis of NIA data, the NIA Working Group has confirmed that the number of K applications from M.D and M.D./Ph.Ds. has declined dramatically, particularly for the K08 award. About half of physician-scientists who receive R01s have never had a previous award on which they were the principal investigator. However, among the half who have received previous awards, the vast majority have received K awards and they achieve their first R01s approximately a decade earlier than those who have not had a previous award.
The NIA Working Group intends to share draft recommendations with a variety of groups in aging research and academic medicine, including the Association of Specialty Professors and the Council of Deans, and to survey applicants and young faculty. The NIA Working Group also will update its findings once the data for FY2014 become available and explore qualitative data to identify potential differences between physician-scientists who receive K awards and those who do not. The final recommendations will be presented to Council at the May 2015 meeting.
Council members suggested that the NIA Working Group look across NIH for a larger pool as it identifies potential differences between physician-scientists who receive K awards and those who do not. They noted the overall shortage in physicians trained in clinical geriatrics and suggested that the NIA Working Group look at the percentage of physician-scientists with K or R01 awards and a specialty certification in geriatrics. Council members also noted a need to increase the amount of additional K award funds and provide more flexibility for awardees to conduct research.
REPORT: WORKING GROUP ON PROGRAM
The Working Group on Program considered one report and seven concept clearances.
Recommendations from Past Meetings: CTAP Report
Dr. High reported that the Clinical Trials Advisory Panel (CTAP) had reviewed three proposals. Although none of the proposals received a recommendation for moving forward, CTAP did recommend two for revision and resubmission.
A motion to approve the CTAP report was forwarded and seconded. The motion passed unanimously.
RFA/RFP Concept Clearances
Bridging the Preclinical-Clinical Gap in AD Drug Development: AD Translational Center for Animal Model Resources and Preclinical Efficacy Studies
The translation of discoveries from animal models to effective treatments has been difficult because animal models might not be good reflections of disease or predictive of patient outcomes. The proposed concept will support uniform testing standards, the creation of new and different animal models, and infrastructure to facilitate the movement of potential therapies through preclinical and clinical development. The Working Group on Program motioned that this concept be approved. The motion was seconded and it passed unanimously.
Collaborative Aging Research Using Technology in the Home (CART) Initiative
The proposed concept, which represents collaboration across Federal entities, will support research that uses highly instrumented homes and home-deployed technologies to study the impact of interventions and assess when older adults may need a transition in care. The Working Group on Program noted that the proposal will allow researchers to test systems that provide the maximum benefit with minimal burden. The Working Group on Program also noted the importance of ethical issues and psychosocial impacts and it was pleased to see an ethics core built into the proposal. The Working Group on Program motioned that this concept be approved. The motion was seconded and it passed unanimously.
Collaborative Network to Advance Delirium Research
The proposed concept aims to support a 5-year, multi-institution, transdisciplinary network to explore mechanisms underlying delirium. The network will include a national research database and harmonize data and definitions. The Working Group on Program agreed that such a network is critical to improve understanding of a problem that is costly but poorly understood. The Working Group on Program motioned that this concept be approved. The motion was seconded and it passed unanimously.
Physiology and Mechanisms of Action of Pro- and Anti-Aging Proteins in Circulation
On the basis of recent findings regarding pro- and anti-aging proteins in animal models, the proposed concept will support research exploring mechanisms in which these proteins are involved, the effects of altering the proteins, and correlations with aging phenotypes and age-related diseases. The concept will employ a cross-disciplinary approach. The Working Group on Program motioned that this concept be approved. The motion was seconded and it passed unanimously.
Short-Term Measurements of Improved Resilience
The proposed concept will support research to develop better tests to measure stress and resilience. Development of such tests, which would be easy to do in the clinic, could facilitate the stratification of populations based on stress responses and improve assessments of potential interventions to expand the health span. After discussing the potential creativity of the research community in this regard, the Working Group on Program motioned that this concept be approved. The motion was seconded and it passed unanimously.
Behavioral Epigenomics of Aging in Twin Studies (BEATS)
Twin studies have played a key role in understanding genetic and environmental influences on long-term behavioral and health outcomes. However, analyses in these studies have primarily been statistical. The proposed concept will support research exploring epigenetic influences related to social and lifestyle aspects. The concept will create a network of existing twin and longitudinal studies and support new applications focusing on behavioral epigenomics. The Working Group noted that in characterizing behavior, the concept will exploit DBSR’s largest strength. The Working Group also suggested that DBSR interact with other NIA Divisions, particularly DAB. The Working Group on Program motioned that this concept be approved. The motion was seconded and it passed unanimously.
Advancing Interdisciplinary Training in Behavioral and Social Research
The proposed concept will support in-depth training, across disciplines both inside and outside behavioral science, to familiarize researchers with language, concepts, and analytic tools in behavioral and social research. In doing so, the concept will foster interdisciplinary collaboration. The Working Group on Program expressed enthusiasm for the concept but suggested that training focus on a few topics in depth. The Working Group on Program motioned that this concept be approved. The motion was seconded and it passed unanimously.
VI. FINAL REPORT: REVIEW OF THE DIVISION OF AGING BIOLOGY
Richard Morimoto, Ph.D., former NACA member, summarized the work and recommendations of the DAB review committee. He noted that, unlike other NIA Division reviews, this review was not designed to align with the structure of the DAB portfolio. Instead, the review committee focused on geroscience, which comprises three areas (epigenetics, proteostasis, DNA damage; metabolism, stress, inflammation; and cellular mechanisms), and on future strategic investments, comprehensive biology, and outreach. In addition, the review committee included individuals who did not work with or were not funded by DAB, including intramural scientists.
Overall, the review committee commended DAB leadership and staff on an extraordinary job of marshaling resources and launching good science, yielding mechanism-based discoveries for translational medicine. The review committee also complemented DAB’s Intervention Testing Program, which has provided a rigorous approach for validating small molecules. Although the review committee acknowledged the historical value of the Nathan Shock Centers, it noted that there were too few Centers to have a nationwide impact. The review committee also noted the continued negative impact of limitations in DAB funding, as well as the closure of important privately funded resources, such as the Ellison Medical Foundation, which has contributed to the careers of junior faculty and promote aging biology among senior researchers. In addition, the review committee suggested that historic boundaries have contributed to artificial divides within NIA. The review committee suggested dissolving some of these artificial divides, for example by identifying research areas of interest to multiple NIA Divisions and, perhaps, by simultaneously evaluating all NIA Divisions.
Dr. Morimoto highlighted some recommendations within the review committee’s focus areas:
Geroscience: continue to advance the Geroscience Initiative, integrate it with other large program areas at NIA, and promote it as an opportunity for international collaboration; continue to highlight the importance of discovery science and a strong mechanistic foundation; emphasize the importance of –omics research as well as single-cell systems; increase research on specific molecules, targets, single cells, and networks as causative factors in aging and age-associated disease; and integrate geroscience with other areas to identify mechanism-based approaches for human health.
Comprehensive biology: emphasize and expand the relationship between basic science and translational efforts, for example by reaching out to the Common Fund, NIH Office of the Director, and other ICs, integrating NIA-supported Centers to make information accessible and facilitate systems biology and bioinformatic approaches, and looking at intersections between basic biology and pathobiology.
Outreach and training: emphasize coordination, not just among NIA and local efforts, but also with international efforts; realign resources within NIA to support new investments in infrastructure; and increase the visibility of larger programs such as the Shock Centers and the AD Research Centers.
Future strategic investments: focus on the integrative effects of physiology on the processes underlying aging, the stochastic nature of aging, and the mechanisms underlying widespread variation among individuals and homeostasis as a driver of aging; reduce or eliminate commitments to genome-wide association studies (GWAS); work with other NIA Divisions and ICs to foster translational research; and exploit opportunities to work with privately funded initiatives, such as Calico, which is supported by Google and Abbvie.
Council members agreed that NIA Divisions should work together more. Although they observed that NIA fosters work across disciplines more naturally than other ICs, they suggested that NIA develop structured incentives to promote integration across Divisions on specific research questions. Some Council members noted that the review of the Division of Geriatrics and Clinical Gerontology (DGCG), which is just beginning, will look at inter-Divisional collaboration and how to measure it.
In response to questions about the committee’s recommendations regarding GWAS, Dr. Morimoto noted that such studies are successful only with large phenotypic effects that are easily measured and that, even if GWAS could serve as discovery tools, the payoff for such studies is unlikely to be high. Although the review committee did not make any recommendations regarding alternative paradigms, it did note that many genomic pathways have been identified and that more work is needed to understand how these pathways lead to cellular health, tissue function, organismal health, and longevity. Dr. Morimoto suggested that understanding how these pathways work together could inform clinical trials.
One member of the review committee added that discoveries regarding the basic biology of aging could have an impact not just on lifespan but also on health span and age-related diseases. He also noted that the rate of such discovery has accelerated exponentially and has the potential to be transformative. However, there are not enough resources to foster this kind of research fast enough. The review committee member reiterated the review committee’s suggestion that NIA work across Institutes and leverage existing investments to facilitate this type of work.
A motion to accept the recommendations of the DAB Review Committee was forwarded and seconded. The motion passed unanimously.
PROGRAM HIGHLIGHTS
Division of Neuroscience (DN): Tau Propagation and Alzheimer Progression
Bradley Hyman, Ph.D., Council member, presented work from his laboratory, which has generated a transgenic mouse model that overexpresses human tau in the entorhinal cortex (EC). With most neurodegenerative diseases, symptoms begin focally then deepen in intensity and spread to other cognitive or motor domains. In AD, this spread is paralleled by the spread of neurofibrillary tangles containing tau. These tangles selectively affect the hippocampus, beginning in large projection neurons within the (EC) and spreading to the hippocampal region and neo-cortex. It is clear that neurofibrillary tangle pathology appears in projection neurons that forge connections between brain areas and that destruction of these connections underlies dementia. The spread of neurofibrillary tangles correlates with both the extent of cognitive disruption and the severity of dementia. However, the mechanism underlying the spread of tangles is not clear.
Dr. Hyman and his colleagues have observed tau propagation from cells expressing the transgene to neighboring cells and, eventually, through the perforant pathway, which terminates in the dentate gyrus. This propagation, which takes approximately 24 months, correlates with degeneration throughout the terminal zone of the perforant pathway. Dr. Hyman and his colleagues have further found that tau is released all the time as part of neuronal function, but that the type of tau changes over time. In older mice, the tau protein becomes phopshorylated and more susceptible to propagation.
In patients, the spread of tangles and the worsening of disease co-occur with amyloid accumulation in the brain. Dr. Hyman and his colleagues have crossed their tau transgenic mouse model with one that exhibits amyloid plaques. Whereas tau propagation takes about 24 months in their tau model, a third of progeny from the cross shows substantial tau propagation at 16 months, and the toxicity associated with this propagation is much worse. Neuronal loss is also accelerated in these mice. Further work demonstrates that tau induces caspase activation, leading to tau truncation and tangle formation.
Additional work in Dr. Hyman’s laboratory suggests a stage at which dysfunctional neurons can be rescued, even after tangles form. This is further supported by work in which suppression of the tau transgene stops the pattern of tau propagation. In addition, in neurons that are still alive but contain neurofibrillary tangles, suppressing the tau transgene actually reverses the formation of these tangles. Thus, tau is emerging as a therapeutic target for slowing the neurofibrillary lesions and pathology of AD.
Discussion focused on the potential implications of this work with respect to olfactory function, circadian rhythms, potential parallel processes in organs outside the brain, and proteins associated with other neurodegenerative diseases.
Division of Geriatrics and Clinical Gerontology (DGCG): Testing the Menopausal Hormone Therapy Timing Hypothesis with the Early versus Late Intervention Trial with Estradiol (ELITE)
Howard Neil Hodis, M.D. discussed the background to the timing hypothesis for menopausal hormone therapy and the rationale for the Early versus Late Intervention Trial with Estradiol (ELITE). Over the past 30 years, several studies have suggested that the risk for coronary heart disease (CHD) or cardiovascular disease (CVD) is lower among women who use hormone therapy during menopause. However, there has been a large discrepancy between observational trials, which have shown hormone therapy to be beneficial, and randomized clinical trials, which have shown no effect or even harm. The timing hypothesis attempts to explain this discrepancy by stating hormone therapy has a differential effect on CVD, particularly atherosclerosis progression and clinical events, depending on when hormone therapy is initiated in relation to menopause. Consistent with this hypothesis, the majority of observational studies have initiated hormone therapy less than 2 years after menopause, whereas randomized trials have typically initiated therapy 10 years or later after menopause. The timing hypothesis is further supported, for example, by meta-analyses showing that CHD and mortality are reduced significantly among women who initiate therapy early after menopause, but that no effects are seen in women who initiate hormone therapy later after menopause. Similar results have been seen in studies such as the Women’s Health Initiative, the Danish Osteoporosis Prevention Study, and the Estrogen in the Prevention of Atherosclerosis Trial (EPAT), among others, with the potential benefit of hormone therapy shifting to a potential harm as therapy is initiated later after menopause.
ELITE enrolled 643 women without pre-existing CVD or diabetes and randomized treatment and timing since menopause. No significant difference in intima-medial wall thickness was seen between placebo and estradiol in the late menopausal group, whereas wall thickness was reduced by approximately 40% with estradiol in the early menopausal group. No differences between estradiol and placebo were observed with respect to coronary calcium, stenosis score, and measures of cognition. ELITE results thus support the timing hypothesis by showing that estradiol therapy reduces atherosclerosis early after menopause but has no effect at later times or on established CVD lesions.
Council members’ questions focused on duration of hormone therapy, how early one must start therapy to receive the maximum benefit, other adverse outcomes, and the possible implications of increasing statin use among the general population.
Division of Aging Biology (DAB): Metabolism of Aging and Age-Related Disease Vulnerability
Rozalyn Anderson, Ph.D., of the University of Wisconsin School of Medicine and Public Health, discussed three projects using calorie restriction (CR) as a model for delayed aging. She explained that aging is the most significant risk factor for many diseases that appear to have fundamental differences in etiology. Identifying aging-related factors that create this vulnerability could facilitate the discovery of potential targets for disease prevention. She particularly showed that aging contributes to metabolic change and that metabolic change is itself a drive of disease.
The first project focused on skeletal muscle loss, a major component of frailty, in the rhesus monkey. Both longitudinal and 24-hour data suggest that CR prevents age-associated declines in physical activity, decreases the metabolic cost of movement, and delays the onset of muscle loss. Work in Dr. Anderson’s laboratory has demonstrated that age-associated vulnerability depends on muscle group, fiber type, and mitochondrial population. Her laboratory has also shown that aging is associated with increased droplet size in intracellular lipid stores.
A second project is focused on the importance of lipid metabolism in disease vulnerability, again in non-human primates. Dr. Anderson’s laboratory has observed differences between overweight animals that develop disease and those that do not. These differences appear in metabolic changes in five lipid classes, not only in serum levels, but also in lipid composition. Changes are particularly evident in two of the lipid classes On the basis of these differences, Dr. Anderson and her colleagues have identified a predictive model, based on serum lipid profiles that could distinguish between healthy and metabolically impaired animals and between pre-impairment states and full impairment among animals that are all equally over-weight.
The third project looks at CR research’s benefits to health as well as to aging. Using multi-tissue gene expression analysis in mice, Dr. Anderson and her colleagues have identified a longevity-associated molecular signature that is conserved across tissues and across CR and genetic models of delayed aging. Elements of this signature also appear in response to effective treatments to reverse metabolic disruption. These observations, along with those from the other two projects, that aging is a major contributor to changes in metabolism and that metabolic change is a major contributor to disease.
Council discussion focused on potential implications and technical challenges for studying age-related vulnerability in humans.
Division of Behavioral and Social Research (DBSR): The Psychology and Behavioral Economics of Poverty
Aging has been correlated both with poverty and with impaired cognition and decision-making. Johannes Haushofer, Ph.D., of Princeton University, described work exploring the hypothesis that the psychological and neurobiological outcomes of poverty affect decision-making in a way that perpetuates poverty. Specifically, Dr. Haushofer’s work has focused on the role of stress.
The majority of Dr. Haushofer’s work has been done at the Busara Center for Behavioral Economics in Nairobi, Kenya. Using a weather shock as a model for increased poverty, Dr. Haushofer and his colleagues assessed income and cortisol levels among Kenyan farmers and metal-workers. As expected, lack of rainfall constituted an income shock among farmers but not among metal-workers, and cortisol levels were elevated among farmers experiencing less rain. The cortisol response to lack of rainfall was less pronounced among farmers who have other sources of income. Consistently, self-reported stress was much higher among farmers who received below-median levels of rainfall.
In collaboration with a charity that provides donations directly to poor homes in Kenya, Dr. Haushofer and colleagues have conducted a randomized controlled trial assessing the effects of increased income on stress. The trial included 1,440 households, 503 of which received unconditional cash donations. On the basis of questionnaire data, families in the treatment group showed increased happiness and large reductions in depression, stress, and cortisol levels. The effects were more pronounced among families receiving larger donations.
He pointed out the evidence shows that both negative and positive income shocks affect stress levels in the expected direction. He next reported a study examining whether high stress levels impair decision-making.
Dr. Haushofer and colleagues conducted a laboratory study in which participants received placebo or hydrocortisone before completing a temporal discounting task. In this study, administration of hydrocortisone was associated with increased discounting, (giving up future gain for a smaller present reward) suggesting that stress can affect decision-making.
Dr. Haushofer raised the issue of how to intervene to break the cycle of poverty and stress. Multiple approaches are being tried. Dr. Haushofer is focusing on increasing wellbeing as a buffer against the effects of stress. He described preliminary results from a pilot study in which some participants were asked to name three things that went well during their day and others were asked to focus on things that had not gone well. Asking people to name three things that had gone well did increase wellbeing.
Council discussion focused on technical aspects of Dr. Haushofer’s work, translation of this work toward families facing food stress in the United States, the potential impact of stress and poverty in early life on executive control, and the potential impact of chronic poverty.
INTRAMURAL PROGRAM REPORT: LABORATORY OF MOLECULAR BIOLOGY AND IMMUNOLOGY
Ranjan Sen, Ph.D., chief of the Laboratory of Molecular Biology and Immunology (LMBI), noted that LMBI has a wide range of interests. However, he focused his presentation on two LMBI projects. The first is exploring mechanisms that generate antibody diversity, which is critical to immunity, and the second is exploring age-associated changes in immune components.
Antibody diversity is achieved through recombination, which introduces double-strand breaks in the gene and brings pieces together in the VDJ exon that encodes the variable region of antibodies. In the mouse, these gene segments are not located in spatial proximity, but recombination brings them together and allows them to form covalent bonds. LMBI is studying conformations in the locus that maximizes the ability of these gene sequences to find each other while minimizing their ability to find other chromosomes. LMBI has studied these structures in primary bone marrow pro-B cells and found that the spatial organization of the locus changes with age in a way that no longer maximizes efficient recombination.
In the second project, LMBI has collaborated with other divisions in the Intramural Research Program to look at age-associated changes in the human immune system. This project involves a longitudinal analysis of age-associated changes in cell populations, using immune phenotyping on stored samples from the Baltimore Longitudinal Study of Aging. This project also will correlate proteomics, gene expression analyses, and epigenomics to characterize the cell populations that do change with age, and it will use these studies to develop algorithms that can be applied to longitudinal samples of peripheral blood mononuclear cells.
Council discussion focused on technical challenges and particularly on the implications of this work for vaccination in older adults and in patients with neurodegenerative diseases.
ADJOURNMENT
The open session of the 124th meeting of the National Advisory Council on Aging adjourned at 1 p.m. on January 28, 2015. The next meeting is scheduled for May 12–13, 2015.
REVIEW OF INTRAMURAL RESEARCH PROGRAM
This portion of the meeting was closed to the public, in accordance with the determination that it concerned matters exempt from mandatory disclosure under Sections 552(b)(c)(4) and 552(b)(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix). 3
CERTIFICATION
I hereby certify that, to the best of my knowledge, the foregoing minutes and attachments are accurate and complete.4
Richard J. Hodes, M.D.
Chairman, National Advisory Council on Aging
Director, National Institute on Aging
Prepared by Robin Barr, D.Phil.
With assistance by Rose Li and Associates, Inc.
For the record, it is noted that members absented themselves from the meeting when the Council discussed applications (a) from their respective institutions or (b) in which a conflict of interest may have occurred. This procedure only applied to applications that were discussed individually, not to “en bloc” actions. (Back to text)
For the record, it is noted that members absented themselves from the meeting when the Council discussed applications (a) from their respective institutions or (b) in which a conflict of interest may have occurred. This procedure applied only to applications that were discussed individually, not to “en bloc” actions. (Back to text)
For the record, it is noted that members absented themselves from the meeting when the Council discussed applications (a) from their respective institutions or (b) in which a conflict of interest may have occurred. This procedure applied only to applications that were discussed individually, not to “en bloc” actions. (Back to text)
These minutes will be approved formally by Council at the next meeting on January 27–28, 2015, and corrections or notations will be stated in the minutes of that meeting. (Back to text)
Attachment A: Roster of the National Advisory Council on Aging
MEMBERSHIP ROSTER
NATIONAL ADVISORY COUNCIL ON AGING
NATIONAL INSTITUTE ON AGING
Chairperson
Richard J. Hodes, M.D.
Director, National Institute on Aging
National Institutes of Health
9000 Rockville Pike
Building 31, RM 5C35
Bethesda, MD 20892
Council Members
Kimberly D. Acquaviva, Ph.D., MSW (2016)
Associate Dean for Faculty Affair
Associate Professor
School of Nursing
George Washington University
Washington, DC 20037
Maria C. Carrillo, Ph.D. (2018)
Chief Science Officer
Alzheimer’ Association
Chicago, IL 60601
Laura L. Carstensen, Ph.D. (2015)
Professor
Department of Psychology
Stanford University
Stanford, CA 94305
Ana M. Cuervo, Ph.D., M.D. (2015) (TFMAR Member)
Professor
Albert Einstein College of Medicine
Department of Development and Molecular Biology
Bronx, NY 10461
Steven R. Cummings, M.D. (2017)
Professor
Department of Epidemiology & Biostatistics
University of California, San Francisco
San Francisco, CA 94107
Jennie C. Hansen, MS, RN, FAAN (2016)
Immediate Past Executive Director
American Geriatrics Society
New York, NY 10036
Kevin P. High, M.D. (2016) (WGoP Member)
Associate Dean for Clinical Research
Department of Internal Medicine
Section of Infectious Diseases
Wake Forest University School of Medicine
Winston-Salem, NC 27157
Bradley T. Hyman, M.D., Ph.D. (2016)
Professor and Director
Department of Neurology/Alzheimer’s Research
Massachusetts General Hospital
Charleston, MA 02129
James L. Kirkland, M.D., Ph.D. (2018)
Professor
Department of General Medicine
Mayo Clinic
Rochester, MN 55905
Eliezer Masliah, M.D. (2018)
Professor
Departments of Neurosciences and Pathology
University of California, San Diego
La Jolla, CA 92093
Richard Mayeux, MD, MS (2017)
Gerturde H. Sergievsky Professor of Neurology, Psychiatry, and Epidemiology
Columbia University
New York, NY 10032
Charles P. Mouton, MD, MS (2017) (TFMAR Member)
Senior Vice President for Health Affairs
Meharry Medical College
Nashville, TN 37208
Ann B. Newman, MPH, MD (2018)
Professor
Department of Epidemiology
University of Pittsburgh, PA 15213
Thomas A. Rando, MD, Ph.D. (2017)
Professor
Department of Neurology and Neurological Sciences
Stanford University School of Medicine
Stanford, CA 94304
Jonathan S. Skinner, Ph.D. (2015)
Professor of Community and Family Medicine
Dartmouth College
Department of Economics
Institute for Health Policy and Clinical
Lebanon, NH 03755
Reisa A. Sperling, MD (2017)
Professor of Neurology
Brigham and Women’s Health Hospital
Harvard Medical School
Boston, MA 02115
Debra Bailey Whitman, Ph.D. (2017)
Executive Vice President, Policy, Strategy and International Affairs
American Association of Retired Persons (AARP)
Washington, DC 20049
EX OFFICIO MEMBERS
Sylvia Mathews Burwell
Secretary
Department of Health and Human Services
Hubert H. Humphrey Building
Washington, DC 20202
Francis S. Collins, Ph.D., M.D.
Director
National Institutes of Health
Public Health Service
Building 1, Room 126
Bethesda, MD 20892
Richard M. Allman, M.D.
Chief Consultant
Geriatrics and Extended Care Services (10P4G)
Veterans Health Administration
Washington, DC 20420
Kenneth G. Pugh, LCDR, MC
Department of Medicine
National Naval Medical Center
Bethesda, MD 20889
Edwin Walker
Deputy Assistant Secretary for Aging
Administration on Aging
Administration for Community Living
U.S. Department of Health & Human Services
Washington, DC 20201
EXECUTIVE SECRETARY
Robin A. Barr, D.Phil
Director, Division of Extramural Activities
National Institute on Aging
Bethesda, MD 20892
