The 97th Meeting
January 31–February 1, 2006
CONTENTS
I. REVIEW OF APPLICATIONS
II. CALL TO ORDER
III. REPORT: TASK FORCE ON MINORITY AGING RESEARCH
IV. REPORT: WORKING GROUP ON PROGRAM
V. PRESENTATION: Findings from Rapid Studies of Responses to Medicare Part D Drug Benefit Program
VI. REPORT: Biology of Aging Program Review
VII. PROGRAM HIGHLIGHTS
VIII. INTRAMURAL RESEARCH PROGRAM REPORTS
IX. REVIEW OF INTRAMURAL RESEARCH PROGRAM
X. ADJOURNMENT
XI. CERTIFICATION
The 97th meeting of the National Advisory Council on Aging was convened on Tuesday, January 31, 2006, at 3:00 p.m. in Building 31, Conference Room 10, National Institutes of Health (NIH), Bethesda, MD. Dr. Richard J. Hodes, 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 31, from 3:00 p.m. to 6:30 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 Public Law 92–463.1 The meeting was open to the public on Wednesday, February 1, from 8:00 a.m. to 2:00 p.m.
Council Participants:
Dr. Elizabeth H. Blackburn
Dr. Melissa M. Brown
Dr. Kenneth V. Brummel-Smith
Dr. John T. Cacioppo
Dr. Carl Eisdorfer
Dr. Linda P. Fried
Dr. Lawrence M. Friedman
Dr. Mary Ganguli
Dr. Alan M. Garber
Dr. Paul Greengard
Dr. Virginia M.-Y. Lee
Dr. Spero M. Manson
Dr. Terry L. Mills
Dr. John C. Morris
Dr. Albert L. Siu
Dr. Mary E. Tinetti
Absent:
Dr. Gary B. Ruvkun
Ex-officio Participants:
Dr. James F. Burris, Department of Veterans Affairs
Ms. Mary Guthrie for Mr. John Wren, U.S. Administration on Aging, Department of Health and Human Services
The Council Roster, which gives titles, affiliations, and terms of appointment, is appended to these minutes as Attachment A.
In Addition to NIA Staff, Other Federal Employees Present:
Dr. Barbara M. Alving, Acting Director, National Center for Research Resources, NIH
Dr. Howard Iams, Social Security Administration
Dr. Raynard Kington, Deputy Director, NIH
Dr. Judith Finkelstein, Center for Scientific Review, NIH
Members of the Public Present:
Dr. Judith Campisi, Lawrence Berkeley National Laboratory, University of California (by teleconference)
Ms. Christy M. P. Gilmore, American Academy of Orthopaedic Surgeons
Dr. Laura Haynes, Trudeau Institute
Ms. Mary Jo Hoeksema, Population Association of America and Association of Population Centers
Dr. Michael Hurd, RAND Corporation
Dr. Rose Maria Li, Rose Li and Associates, Inc.
Dr. Jack McArdle, University of Southern California
Dr. Daniel McFadden, University of California, Berkeley
Ms. Eileen Resnick, Society for Women’s Health Research
Ms. Carol Schutz, Gerontological Society of America
Ms. Angela Sharpe, Consortium of Social Sciences Associations
Dr. Dellara Terry, Boston University Medical Center
Dr. David Weir, University of Michigan
Dr. Berislav Zlokovic, University of Rochester
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 552b(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix). 2
A total of 974 applications requesting $915,768,722 for all years underwent initial review. The Council recommended 543 awards for a total of $612,124,921 for all years. The actual funding of the awards recommended is determined by the availability of funds, percentile ranks, priority scores, and program relevance.
Dr. Hodes welcomed members to the open session of the National Advisory Council on Aging and called the meeting to order at 8:10 a.m. on Wednesday, February 1, 2006.
Director’s Status Report
Dr. Hodes presented the total budget for the NIA, in both current and constant dollars, for fiscal years (FY) 1996 to 2006. The NIA appropriation level for 2006 is $1,037,278,000, of which 67 percent is devoted to research project grants, 8 percent to centers, 3 percent to other research, 2 percent to training, 6 percent to contracts, 10 percent to intramural research, and 4 percent to research management and support. Dr. Hodes observed that since its peak in 2003, the budget has decreased in constant dollars. Success rates also have decreased since 2003, and paylines will be substantially lower than the 17.9 percent originally estimated for FY 2006. To modulate the impact of a decreasing budget, a new NIH Financial Policy for Grant Awards dictates that noncompeting awards in FY 2006 will be funded at 97.65 percent of the amount indicated for the FY 2006 budget period in the Notice of Grant Award issued in the previous budget year. This reduced amount will serve as the base for out-year funding. The amount provided for competing awards will be managed to an average amount equal to FY 2005 levels. The FY 2006 policy includes the provision of a 3-percent escalation factor for subsequent years on competing research project grants, which are not based on modular applications; how the escalation for noncompeting awards will be handled has not been determined. Dr. Hodes stated that the President was expected to announce the FY 2007 budget during the next week.
In response to questions from Council members, Dr. Hodes clarified that new grants will be reduced again by an average of 18 percent of recommended levels and that the reduction in noncompeting awards offsets otherwise more severe cuts. He added that the current estimate (posted on the NIA Web site) reflecting an intention to pay to about the 10.5 percentile may change once all applications are received.
Council members expressed concern that budget limitations will discourage young and new investigators. Dr. Hodes responded that rather than have a separate payline or different review criteria for new investigators, the NIA monitors the proportion of awards to new investigators. Roughly 23 percent of awards are granted to new investigators, and this proportion has not declined in the short term. Dr. Hodes assured Council members that if this proportion were to decrease, then the NIA would discuss with the Council additional approaches for encouraging new investigators.
Dr. Hodes then discussed the Office of Portfolio Analysis and Strategic Initiatives (OPASI). Although the NIH has done well at establishing priorities and planning research at the Institute and Center (IC) level, there is a less explicit mechanism for evaluating research investments across ICs. OPASI will assess research initiatives and programs across all ICs and use this information to plan research in a more coordinated fashion and to improve the effectiveness of NIH programs. This applies particularly to trans-NIH ideas, such as the Roadmap initiative, which transcend individual ICs.
Dr. Hodes outlined the proposed structure of OPASI and emphasized that this office would serve as an incubator for trans-NIH initiatives. He further noted that input to OPASI, particularly for identifying scientific initiatives, would be informed by portfolio analysis and issues of public health and burden of illness. Input also could come from stakeholders, a regular Roadmap-like planning process, and Office of the Director program offices such as the Office of Behavioral and Social Science Research and Office of Research on Women’s Health. Decision-making for OPASI activities will be done by a council of approximately 30 members, including representatives from each IC. Each IC will nominate three candidates from their individual councils—two scientific advisors and one lay member—and the NIH Director will make the final selections and ensure a broad range of expertise. A Common Fund derived from funds appropriated to each IC, but not from each IC’s base, will be used to incubate program development. The amount of time during which an initiative is supported by the Common Fund will be limited. At the end of that time, an initiative will move to the most appropriate IC for continued support. Thus, OPASI will provide a means for identifying and supporting new opportunities and ideas.
Dr. Hodes explained that current Roadmap funds, which comprise about 1.1 percent of the total NIH budget for FY 2006, will serve as a baseline for the Common Fund. The percentage of NIH funds devoted to the Roadmap is expected to increase to about 1.7 percent in FY 2008. Over time, contingent upon the growth of the NIH budget, the Common Fund will increase to up to 5 percent of the total budget. This increase will depend on and be consistent with identified trans-NIH scientific opportunities and public health needs. This approach is expected to be more efficient and effective than tapping each of the ICs on an ad hoc basis each time there is a trans-NIH priority and is consistent with recommendations by external groups. A search for an acting director for OPASI will be under way soon.
Council members questioned whether any retrospective evaluation of the Roadmap had taken place. Dr. Hodes responded that it is early to evaluate outcome. Some initiatives have been under way for up to three years. He emphasized that OPASI and the Common Fund aim to open opportunities for new ideas, which is one reason for examining the current portfolio to identify less productive or completed projects including termination of completed or less productive programs. Legitimate evaluation by OPASI is a central part of the planned activities.
One Council member noted the collaborative and diverse nature of the NIA science and questioned whether the NIA would be as competitive for common funds as other ICs that traditionally have not been as collaborative. Dr. Hodes responded that the level of NIA involvement in the Roadmap has varied. Some initiatives, such as the development of molecular libraries, the exploration of signaling pathways, and proteomics, will serve the NIA as well as other ICs, although NIA-supported investigators have not participated actively. The NIA has been involved with efforts to modify the clinical research infrastructure, and the NIA has had a substantial representation in interdisciplinary research. Dr. Hodes reiterated that research supported by OPASI only would be supported for a limited amount of time and that, if the research must continue beyond that time, it would be supported by the most relevant IC or ICs. Once the IC assumes responsibility for a project, the NIH Director could consider a decision to propose an increased appropriation to that institute or center.
Another Council member questioned how research and training, particularly interdisciplinary training grants, would function within OPASI. Dr. Richard Suzman commented that aging is the final common pathway and that fact has made aging a leader in interdisciplinary research. Yet he was disappointed in the Roadmap interdisciplinary training grants and has been frustrated by reviewers’ attitudes to integration of new disciplines with aging and geriatric research.
Dr. Hodes circulated for Council information a compendium of the last quarter’s public outreach activities of the Office of Communication and Public Liaison.
Announcement of Staff Changes
Dr. Hodes welcomed Ms. Kathie Reed, who joined the NIA as head of the Office of Planning and Evaluation, and announced that Dr. Miriam Kelty, Director of the NIA Office of Extramural Research, is retiring. He credited Dr. Kelty with making the extramural programs successful over the years, and he observed that she is widely regarded throughout the NIH as a leader in research administration, including in the area of ethics and bioethics. Dr. Kelty commented on the maturation of the Institute during her tenure and the exciting, important, and challenging research at the NIA. During her time at the NIH, in addition to aging research, she particularly enjoyed working to stimulate emerging fields such as behavioral medicine and health psychology, and empirical research in bioethics. She thanked the Council for its acknowledgment and announced that Dr. Robin Barr would be the Acting Director until a permanent Director is named.
Future Meeting Dates
May 23–24, 2006 (Tuesday and Wednesday)
September 26–27, 2006 (Tuesday and Wednesday)
January 30–31, 2007 (Tuesday and Wednesday)
May 15–16, 2007 (Tuesday and Wednesday)
September 25–26, 2007 (Tuesday and Wednesday)
Consideration of the Minutes of Last Meeting
The minutes of the September 2005 meeting were considered. A motion was made, seconded, and passed to approve the minutes.
In his report on behalf of the Task Force on Minority Aging Research, Dr. Spero Manson focused his presentation on two areas: (1) full Council review of minority aging and health disparities research supported by the NIA and (2) Council review and approval of the Institute’s adherence to the NIH gender and minority inclusion policy. He also mentioned an ongoing planning effort around a K-award mechanism to promote aging research careers and diversity.
In 1999, the Task Force conducted a systematic review of the NIA’s portfolio to identify relevant projects in minority aging research and generated the following eight recommendations:
- Eliminate health disparities;
- Define race, culture, and socioeconomic status;
- Implement longitudinal and life-course studies;
- Integrate biology, genomics, and genetics of aging;
- Refine methods and strategies;
- Improve recruitment and retention of minorities in clinical research;
- Clarify and strengthen NIH policy on inclusion of minorities in clinical research; and
- Build capacity for and enhance training and information dissemination.
The Task Force now has completed an updated review to assess the NIA’s progress since these recommendations were outlined. The NIA’s substantial investments in minority health and health disparities research have involved the NIA’s intramural research program, minority recruitment efforts at the San Antonio Shock Center, five major longitudinal studies, Alzheimer’s disease (AD) centers and satellites, and Resource Centers on Minority Aging Research (RCMARs). NIA efforts also have yielded several benchmark publications, including Understanding Racial and Ethnic Differences in Health in Late Life, which was supported by the NIA Behavioral and Social Research (BSR) Program. The Task Force’s new report includes metrics regarding advances and examines areas of change. Most notable are increases in the numbers of supplements RCMAR pilot projects, RCMAR publications, and the citation of minority health and health disparities research papers in NIA Planning Source Books. The Task Force also noted a modest increase in minority enrollment in NIA-supported research.
Dr. Manson reported that the Task Force continues to consider the status of minority investigators in aging research, particularly how supplement awardees track through other funding mechanisms such as small grants, career development awards, and R01 grants. The emphases on the recruitment and training of racial and ethnic minorities, and on efforts to broaden capacity and diversity within the NIA anticipated the broad concerns underscored by research reports from the NIH (The NIH Minority Research Recruitment Program Report) and the Institute of Medicine.
Dr. Manson highlighted the following as major recommendations from the 2006 review of minority aging research and training within the NIA:
- Research
- Generate a Program Announcement or Request for Applications addressing factors contributing to health differentials in HIV, metabolic syndrome, obesity, congregate living (extended-care facilities), and older minority workers.
- Continue to enhance minority recruitment and retention efforts with attention to the roles of community stakeholders.
- Training
- Expand the RCMAR program to include a center in the central United States.
- Retrofit the T35 program for post-baccalaureate training of underrepresented minority trainees.
- Collaborate in establishing an NIA-wide system for monitoring the progression of underrepresented scientists in training programs.
Dr. Manson concluded that there is active research on issues relevant to minority aging and health disparities across each NIA program. NIA-supported research addresses most, if not all, major factors thought to contribute to racial and ethnic differences in health and is making a difference in the methods and practices used in recruiting and retaining minority elders in aging research. He also made a specific recommendation that the Institute establish an electronic system for tracking minority participation and career development to document the NIA’s progress and the return on its investment.
Next, Dr. Manson and Dr. J. Taylor Harden briefed the Council on NIH policy requiring that the Task Force review, at least annually, the appropriate inclusion of subjects by gender, race, and ethnicity in current research projects; certify that the NIA is in compliance; and make this information available to the public. The NIH’s policy for inclusion reporting is determined by the Office of Management and Budget’s standards for racial and ethnic considerations, which were changed in 1997 to allow for multiple race reporting, Hispanic ethnicity reporting, and the addition of a Hawaiian/Pacific Islander category. Cost is not an acceptable justification for exclusion, and the NIH must support outreach efforts to recruit and retain women, minorities, and their subpopulations in clinical studies. Dr. Harden reminded the Council that the NIH Definition of Clinical Research includes patient-oriented research, epidemiologic and behavioral studies and outcomes, and health services research. She mentioned the Outreach Notebook for the Inclusion, Recruitment, and Retention of Women and Minority Subjects in Clinical Research, which was published in 2003, and pointed to additional guidance, including the NIH Policy on Reporting Race and Ethnicity Data: Subjects in Clinical Research and the 2001 NIH Guide notice.
Dr. Harden presented population growth data from the National Center for Health Statistics that project increasing numbers and diversity of the U.S. population aged 65 and older in coming decades. A total of 490,000 individuals participated in NIA extramural projects in 2005, compared to 599,000 individuals in 2004, with the groups evenly divided between males and females. The majority of research participants were white (72 percent compared to 70.6 percent in 2004). The percentage of American Indians/Alaska Natives nearly tripled from 0.38 percent in 2004 to 0.9 percent. In contrast, the percentage of Hawaiian and Pacific Islanders declined from 0.7 percent to 0.4 percent. The percentage of Asians declined from 15.4 percent to 9.3 percent, while the percentage of Hispanics or Latinos increased from 3.4 percent in 2004 to 8.4 percent in 2005. The proportion of Black or African American was relatively unchanged at about 10.0 percent. The percentage of “unknown” or “not reported” increased from 2.4 percent to 6.2 percent. In addition, the percentage of participants reporting more than one race increased from 0.6 percent to 1.0 percent in 2005.
A motion was made, seconded, and passed unanimously to accept the 2005 report on inclusion of women and minorities in clinical research as being in compliance with the NIH guidelines for inclusion of minorities and women.
Before reporting on the deliberations of the Working Group on Program (WGOP), which met on January 31, 2006, Dr. Linda Fried expressed great appreciation for Dr. Kelty’s leadership of the Council. Council members were referred to statistical data on the NIA extramural programs that were included in their packets.
Dr. Fried reported on ongoing discussion concerning two related topics: Physician researchers in geriatrics and an aging population’s future needs that can be addressed by research. These discussions led to the establishment of an ad hoc group last year, chaired by Dr. Marie Bernard, to evaluate the status of the research workforce. Dr. Bernard and Dr. Robin Barr provided data to the WGOP on NIA-supported R01 grants for FY 2005, which showed that applicants with M.D.s were as successful as those with Ph.D.s in receiving awards. However, the total number of awards to physician researchers has not increased since 1980. Awards to physician researchers comprised 20 percent of all awards; the percentage to M.D./Ph.D. was about 9 percent. Physician researchers were represented particularly in the Geriatrics and Clinical Gerontology (GCG) Program, the Neuroscience and Neuropsychology of Aging (NNA) Program, and in clinical trials.
Dr. Fried summarized the Council’s main concerns as follows:
- Stability and the relative dearth of physicians conducting aging research despite several innovations that the NIH and/or NIA has implemented, including the creation of new T35 grants, implementation of loan-repayment programs to increase the number of physicians electing to do postdoctoral research, allowing physicians on K awards to charge some salary to R01 grants, the Beeson K award program, and development of mechanisms to allow multiple principal investigators.
- Lack of an overall increase in the number of physician researchers and jeopardy for what is perceived as a fragile workforce. There are very few senior physician researchers in the field of aging, and those researchers are burdened with heavy mentorship responsibilities. Once they retire, the ranks of senior-level researchers will be depleted. Furthermore, because of fluctuations in research funding, there are few mid-career researchers available to assume mentorship roles, which threatens to impact severely on junior researchers.
- The pressures of clinical care in the face of an aging population make essential the creation of academic tracks that support clinical careers without research.
Other concerns include constraints on the NIH budget that compromise the ability to fund research; the loss of early-career funding from Foundations that used to fill a particular niche; and disincentives to the physician to pursue a research career.
Dr. Bernard emphasized the importance of clarifying the relevance of research questions that clinical researchers are apt to raise, particularly questions regarding improved care for elders and health economics. She added that available data, including labor market analyses, have documented the need for physician researchers though a desirable number to fill the need is not known. Dr. Bernard recommended a task force and a State of the Science conference to define the most pressing research issues in improving the care of an aging society. This initiative should represent the perspectives of all four NIA programs, increase understanding of the questions physicians are most likely to ask, determine whether the overall NIA portfolio provides a good match for questions the public wants answered, and generate recommendations to the NIA. The GCG Review Group also will consider pressing clinical questions for which research needs to develop answers.
In light of the inadequate number of physicians in the aging research pipeline, the loss of funding to bring more physicians into research on aging, and the need to protect early career awards, the Council proposed the following:
- The NIA staff should review the training page on the NIA Web site as well as information on clinical research, and develop a career development time line along with the funding mechanisms most appropriate for each stage.
- A small working group should meet before the next Council meeting to determine what the NIA should do to enhance the physician researcher workforce.
- Relevant extant reports on the unique role of physicians in clinical research and where they can make contributions should be provided to Council members.
- The next WGOP meeting should consider further the development of a task force or a state-of-the-science conference to address broad questions about public health and clinical concern.
Planned Adjustment for New Study Sections Related to Research on Aging
Dr. Kelty reported on progress related to two new study sections established with active NIA collaboration to review aging research at the Center for Scientific Research: (1) Aging Systems and Geriatrics (ASG) and (2) Cellular Mechanisms of Aging and Development (CMAD). As the science of aging has evolved, there has been some concern about the balance of workload, the inclusion of appropriate expertise, and whether applications are assigned to the appropriate study sections. The NIA, the Center for Scientific Review, and the heads of the study sections and Integrated Review Group have been undergoing a planned adjustment process. Dr. Kelty asked Council members to nominate potential members for study sections, preferably by forwarding names and curricula vitae to the relevant scientific review administrator (Dr. Francois Boller for ASG and Dr. James P. Harwood for CMAD) or to the head of the Integrated Review Group
(Dr. Sherry Dupere). She also reminded the Council that because of geographic distribution requirements, gender and minority requirements, and other constraints, nominees may not be considered immediately, but their names will be kept on file for up to four years.
Action: Statement of Understanding
The Statement of Understanding between the Council and Institute staff is acted on once a year to allow the business of the Institute to continue between Council meetings. Dr. Kelty sought Council approval to modify the Statement of Understanding to delete Item 4, because it has been rendered obsolete given that the NIH has changed the way it pays reviewers. A motion was made, seconded, and passed unanimously to approve the Statement of Understanding as modified.
Geriatrics and Clinical Gerontology (GCG) Review Group
Dr. Mary Tinetti, Chair of the GCG Review Group, reported that the GCG review scheduled for May 2006 is in its planning stages. The group covers a broad range of expertise and has developed a tentative agenda for the review, which will focus on defining health burdens and future directions. A conference call will be held in April to clarify the agenda. Dr. Kelty welcomed all interested Council members to participate.
Action Plan on Research on Menopause-Related Symptoms
Dr. Sherry Sherman reported that the development of the Action Plan on Research on Menopause-Related Symptoms followed from a State of the Science conference held in March 2005, for which the NIA served as the lead Institute. The conference was cosponsored by several agencies within the NIH and the Department of Health and Human Services, including the National Center for Complementary and Alternative Medicine, the National Institute of Child Health and Human Development, and the NIH Office of Research on Women’s Health. The NIA is accepting nominations for members of an advisory panel, which is expected to meet twice in 2006 to identify and prioritize research directions. The advisory panel will consider the most burdensome symptoms, identify target populations and research designs, and identify promising strategies with particular attention to long-term risks, adverse events, various remedies, and varied therapeutics including alternative medicine. This activity should be completed in FY 2006.
The next presentations exemplify the NIA’s agility in bridging public health imperatives and research opportunities. The Health and Retirement Study (HRS), which is supported by the NIA’s BSR Program and by the Social Security Administration, and a set of Internet panels, one of which is cofunded by the NIH Office of Behavioral and Social Sciences Research, are being used to understand the impact of the implementation of Medicare’s Part D drug benefit program.
Before the Medicare Part D program, about 26 percent of seniors had conventional Medicare Part A without supplemental drug coverage and, therefore, had to pay for their prescriptions. The new program provides prescription drug coverage through Medicare-approved plans with substantial protection against catastrophic drug costs. Private insurers and health maintenance organizations (HMOs) compete to offer coverage, and this competition, in addition to consumer self-interest, is expected to make the market self-regulating, with minimal supervision by the Centers for Medicare and Medicaid Services (CMS).
Several problems with the launch of Medicare Part D have been reported. Consumers face difficulties in obtaining enough information and understanding to make satisfactory choices. The management of consumers’ transitions from pre-existing therapies to plan formularies and approvals is flawed, and problems with understaffing have resulted in inadequate information and guidance to seniors, doctors, and pharmacies. Longer-term issues include: (1) Uninformed consumers: Many seniors have not paid attention or made reasoned choices or have not enrolled in any plan; (2) Adverse selection: Healthy seniors must enroll to achieve actuarial balance; (3) Moral hazard: The increases in the number of prescriptions as people obtain drug coverage.
In addition, the reluctance of insurers to accept consumers with conditions that require “designer” drugs will lead to conflicts between insurers and pharmaceutical companies. Medicare Part D runs the risk of falling short unless therapies are made affordable for the Medicare population, satisfactory alternative plans are made available, and the ability of seniors to make sound choices is ensured.
To study these issues, five research projects are in place. Another study will focus on low-income Americans who are eligible for subsidies and identify ways to increase their enrollment into Part D.
Dr. Suzman introduced the panel of speakers. Dr. Daniel McFadden, Professor of Economics at the University of California, Berkeley, is currently President of the American Economic Association and winner of the 2000 Nobel Prize in Economics. Dr. David Weir is Associate Director and co-Principal Investigator of the HRS at the University of Michigan and a former NIA K01 career awardee. Dr. Jack McArdle is Professor of Psychology at the University of Southern California and also co-Principal Investigator of the HRS. Dr. Michael Hurd is Director of the RAND Center on Aging, as well as Principal Investigator on an NIA program project, and co-Principal Investigator of the NIA-funded RAND Roybal Center for Financial Decision Making.
A. Medicare Prescription Drug Coverage: Consumer Information and Preferences
Little is known about how eligible individuals make their enrollment and plan choices. In the week before enrollment opened, Dr. McFadden’s research team administered a survey on prescription drug use and enrollment intentions to a sample of 1,996 Medicare-eligible U.S. residents aged 65 and older. He noted that the results were obtained within 7 weeks, including responses from the elderly with health issues. For these respondents, the team constructed measures of current prescription drug use and pharmacy bills, and then related knowledge about the Part D program and intentions to enroll to sociodemographic and health characteristics of respondents. The team found that despite the complexity of the program’s competing plans, which can differ in premiums and coverage, a majority of the Medicare population had at least some knowledge of Part D (61 percent), and a substantial majority (87 percent) were likely to enroll. However, low-socioeconomic status elderly with poor health and cognitive impairment were significantly less informed than other groups about Part D and may fail to take advantage of the program. Intended enrollment was significantly less likely among those poorly informed and among those in good health. Enrollment was significantly more likely among those with higher pharmacy bills and significantly less likely among those who currently pay their own pharmacy bills. Seniors with prescription drug coverage averaged 4.4 prescriptions per month, and those without averaged 3.3.
For unhealthy persons, enrollment should be an attractive option that locks in low premiums and provides insurance. This option can be priced, based on a person’s current age and health status, using a stochastic program that assesses probabilities of new health conditions and distributions of therapy costs. Preliminary results suggest that to minimize the expected present value of out-of-pocket costs, persons whose current pharmacy costs total more than $802 annually should enroll now in Medicare Part D. Those whose pharmacy costs are less than $500 should delay enrollment in Part D. About 10 percent of the Medicare population expressed the intent to delay enrollment, even though they would benefit from enrollment, whereas close to 20 percent expressed their intention to enroll at the outset, even though they would benefit from delayed enrollment.
In presenting respondents with hypothetical alternatives, Dr. McFadden reported that many elderly consumers undervalued the insurance features of Part D. The vulnerable have less information and were more likely to make poor enrollment and plan choices as a result. Procrastination is a common behavioral response to ambiguity, and when nonenrollment is the default, this makes suboptimal decision-making likely. He noted that many who intend to enroll will miss the May 15 deadline.
Dr. McFadden concluded that Part D is in jeopardy of failing to meet its objective of making prescription drugs available to most elderly at affordable costs.
B. The Health and Retirement Study
Dr. Weir described plans for the ongoing longitudinal HRS to support research on Medicare Part D. The HRS already has collected 14 years of core survey data on prescription drug use, spending, health, income, cognition, and family. The original 1992 cohort includes persons between the ages of 51 and 61 years. In 2006, these participants will be between 65 and 75 years old. The effects of Part D will be assessed in 2006 and future waves. To complement the core survey, the HRS conducted mail surveys in 2005 to obtain detailed lists of medications used and data on dosage, satisfaction, side effects, and compliance, and will do so again in 2007.
Dr. Weir then presented early results from the 2005 mail survey on knowledge, attitudes, and intentions regarding Part D. The survey, conducted from mid-October to late November, had a sample size of 4,600 with a response rate of 88 percent (80 percent among African American respondents). The study focused on five groups corresponding to categories targeted by the CMS: (1) those with good employer (retiree) prescription drug coverage, (2) those in Medicare HMOs, (3) those with dual eligibility for Medicaid, (4) those who are low income and eligible for subsidies for Part D, and (5) all others. Data from the 2004 wave of the HRS showed that these groups differed widely in economic resources, cognitive ability, and Internet access. Although the low-income group would gain the most from Part D, it had the lowest cognitive resources and faced the greatest cognitive demands in navigating the system, applying for subsidies, and choosing the right plan provider. Thus, this group experienced the greatest amount of stress in trying to understand the changes to Medicare. Satisfaction with current prescription coverage depended on out-of-pocket costs per prescription and on restrictions, particularly formulary limits. For all respondents, about 15,000 different drugs were listed. For all drugs, 91 percent of respondents said that the drug was important for their health, and 53 percent thought it was the best one available. Before Part D, respondents were generally highly satisfied with their coverage, although they were dissatisfied with formularies and high costs. There was little dissatisfaction with medication regimens. Most respondents reported that they had not received key pieces of information needed to guide their decisions about Part D enrollment. Retirees who had received letters from their employers indicating that their current plans met or exceeded Part D standards faced less uncertainty and were less likely to enroll in Part D. However, only 30 percent of these respondents received employer letters.
Dr. Weir concluded his presentation by noting opportunities for future research, which would benefit from data sharing by the CMS. Part D claims could be examined to track medications used, timing, and prescriptions that were missed. The CMS Online Plan Finder could be replicated on HRS survey respondents, and data could be compared with actual choices in 2006.
C. Longitudinal Studies on the Dynamics of Cognition in the Health and Retirement Study
Dr. McArdle reported that the current HRS cognitive measures include several well-known cognitive measures that are intentionally short tests and have good psychometric properties for mental alertness, verbal abilities, and memory, and they have been used widely in other studies. Measures designed initially as indicators of test validity, dementia, and impairment, also may provide information about seniors’ capacity to manage real-life events. This is particularly relevant in light of possible cognitive declines associated with aging; factors involved in decisions about retirement, pension planning, and selection of health insurance; and cognitive inequalities that may play key roles in the dynamics of income, health, and socioeconomic inequalities.
The inclusion of cognitive measures is atypical for a nationally representative population survey, especially a telephone survey, but offers the possibility of yielding a great deal of unique information. On the basis of modeling cognitive data with respect to age changes, educational and gender differences, and other demographics, Dr. McArdle reported that (1) cognitive scores decline substantially with age, especially after the age of 80; (2) these cognitive changes are related to other demographics, particularly educational attainment, but the changes are similar across HRS cohorts; (3) there are two specific cognitive factors measured by the current HRS scales—memory and intactness; and (4) the survey techniques used in the HRS provide the same measure of cognition, regardless of whether the interview is done repeatedly in-person or by phone. The research team is experimenting with new ways to measure additional cognitive functions such as broad reasoning and processing speed.
These cognitive skills may be germane to decisions about retirement and pension planning and the selection of health insurance, and this may create additional “cognitive inequalities.” The 2005 HRS prescription drug mail survey questions were merged with the cognitive data, and analyses of some basic questions about cognition and the use of Medicare Part D prescription drug benefits suggest that: (1) there were many group differences in the impacts of cognition on the choice of the appropriate prescription drug enrollment plan; (2) cognition was strongly related to the responses to problems, knowledge, and enrollment but does not seem to be a complete mediator of the demographic features of prescription outcomes; (3) cognitive intactness was a clear cognitive requirement for any prescription decision, but numeracy was the best additional cognitive variable in predicting enrollment; (4) cognition needs to be considered in the context of the coverage plan in order to establish the best decision for an individual; and (5) other variables measuring broad cognitive reasoning, as well as independent measures of risk style and literacy, are needed.
D. Socioeconomic Status, Knowledge of Drug Costs, and Choice
Dr. Hurd presented preliminary results from a survey administered in mid-January 2006 to assess possible reactions to Medicare Part D. The American Life Panel, an ongoing RAND Internet panel of respondents aged 40 years and older, responded to a questionnaire that assessed knowledge about the cost of prescription drugs, the risk of future costs, anticipated changes to drug use if they lost coverage, and rankings of hypothetical prescription coverage plans. About 90 percent of respondents knew their monthly and annual out-of-pocket costs, but there was widespread lack of knowledge about total costs, particularly among those with low income or in poor health. These results imply that individuals most in need of prescription drugs or least able to afford them have the least information about choosing an optimal prescription drug plan under Part D. There also was widespread perception of increased out-of-pocket costs; the actual mean monthly cost as reported in the survey was $40, but the anticipated mean was $63.
When asked what they would do if they had to pay the full cost of their prescriptions, about half of all respondents would reduce spending, but 68 percent of respondents in the lowest income quartile and 70 percent of those with the worst health would reduce spending. Most would reduce costs by decreasing the number of prescription drugs they took or the dosage of their prescription drugs. To the extent that these medications are necessary to maintain health, these reductions would impact negatively on the health of the population. When respondents were asked to rate hypothetical insurance plans, most were willing to pay for protection if their costs exceeded $3,000 per year, and they were willing to pay more for access to brand-name drugs.
E. Discussion
The standard Part D plan is offered at an annual premium of $444, with a deductible of $250. However, there is a “doughnut hole,” in which consumers must pay out of pocket once their prescription costs reach a certain level; they are covered after their costs reach an even higher level. In addition, approved plans must have formularies with at least two drugs in each therapeutic category. Private insurers may offer plans that are comparable to standard plans or they may offer enhancements such as no deductible, doughnut hole coverage, or broader formularies.
Concern was expressed that patients may forgo a drug to avoid falling in the doughnut hole or that their physicians may overprescribe to get them beyond the doughnut hole. Dr. McFadden and Dr. Weir agreed that this was an important issue for which more information is needed. However, knowledge about the relationship between the number of prescriptions and prescription drug costs can be used to estimate the effects of the doughnut hole.
In response to a question about choices made by those with low cognitive function, Dr. McArdle commented that studies have not yet accounted for caregivers who help Medicare-eligible individuals make decisions. With respect to compliance, Council members noted data indicating that a patient’s perception of the severity of his or her illness is a strong indicator of adherence. Both of the issues of surrogate decisionmaking and compliance, as well as racial and ethnic contributions to trends, can be assessed over time with longitudinal data from the HRS.
In terms of research and policy issues arising from these studies, Dr. McFadden highlighted three research issues of highest priority: (1) the extent to which these plans can survive in their current forms, especially in cases with unsustainably low premiums used to encourage initial enrollment; (2) monitoring of the prescription drug market as Part D is implemented in terms of prices, usage, and health outcomes; and (3) efficacy and cost benefit of expensive, individualized drugs as they become available and whether Part D will cover them. Dr. Hodes noted as well an interest in understanding not just utilization patterns, but more importantly, how utilization relates to health outcomes.
Council members were provided a copy of the report from the BAP Review. The 1-day review was held on September 26, 2005, and was preceded by a series of planning teleconferences, committee review of prepared materials, and e-mail discussions. Dr. Judith Campisi, who chaired the review committee and joined the Council by phone, described the composition of the committee and praised the BAP’s exceptional program. She summarized the main findings, highlighting two overarching recommendations: (1) rather than funding all meritorious applications in saturated areas, streamline the BAP portfolio based on programmatic needs, investigator promise, potential for advancing the understanding of the aging process and for developing rational preventive or intervention strategies; and (2) develop common metrics to facilitate evaluation of success across NIA programs. Dr. Campisi then discussed the review of specific BAP activities.
The Nathan Shock Centers, which were established in 1995 to develop an infrastructure that would accelerate discoveries in basic aging research, account for less than 3 percent of the total BAP budget. The review committee concluded that the Shock Centers are an excellent and cost-effective investment in infrastructure. However, there is no centralized mechanism to facilitate communication among Shock Centers. The committee recommended that a Web site for Shock Centers be developed to increase communication about available resources and help reduce duplication of efforts. This site could be linked to other programs, for example, the Alzheimer’s Disease Center program.
The review committee expressed concern about a general decline in the number of funded training grants as well as the amount of money allocated toward training. The BAP should consider increasing its support for T32 training and F32 fellowship grants, and consider support for training programs that focus on early stage graduate students and medical students in their last year of training or additional years of fellowship. There are times when funding for students is difficult to obtain, and would be relatively inexpensive. The review committee also recommended that the NIA consider funding F31 individual predoctoral fellowships, broadening the expertise on T32 review committees to include investigators who direct training grants outside of the field of aging, and relaxing Institutional commitment requirements for the K01 and K08 training awards so that new researchers entering the job market have enough support to be competitive.
Another area of focus for the review committee was the BAP Office of Biological Resources and Resource Development. The committee reviewed this office favorably and noted its effectiveness at providing resources for investigators. The committee encouraged the office to continue to take advantage of NIA- and NIH-wide resources and to continue interaction with centers such as the Shock Centers. Specific recommendations were to (1) consider increasing the number of mutant or knockout mouse models available, (2) organize a workshop on comparative genomics, and (3) add frozen bone marrow samples to the tissue bank.
Dr. Campisi then briefly summarized recommendations related to two major research branches of BAP: The Genetics and Cell Biology Branch and the Systems Branch. The review commended both branches for the quality and breadth of their grant portfolios and for their leadership in developing emerging areas of basic aging research. The committee recommended that both branches interact with the BSR’s prospective epidemiology cohort studies, consider the translational potential of BAP research, and avoid funding trendy areas that do not focus on aging. The committee also recommended that the BAP consider, on an ongoing basis, the appropriateness of the BAP branch structure in supporting current advances and anticipating future advances in the field of aging. The BAP also should help basic scientists apply their research to clinical problems, including facilitating interactions with clinical scientists.
Dr. Hodes thanked the review committee for its recommendations. He acknowledged the ongoing need to balance the focus on excellence in science against areas of scientific excitement that are less relevant to the Institute. He also noted the challenges in having to decide at times what science falls within the domain of aging research. Now that a level of excellence has been achieved for areas most focal to aging research, the BAP and the NIA must ensure that these programs are taken into account for future resource allocation and program development.
One Council member observed that the T32 training programs repeatedly re-emphasized the same areas and, therefore, did not allow for more perspectives as science evolves. It is important to assess the training grant review groups and ensure the inclusion not only of individuals experienced in aging research, but also of individuals who can provide different perspectives.
Another Council member questioned the specific recommendation for the Genetics and Cell Biology Branch to reduce its emphasis on biomarkers. Dr. Campisi responded that there had been a 10-year initiative to search for biomarkers but that this initiative had not been successful. It is not clear how to define a good biomarker for aging, how to identify it, or how to use it. If a viable scientific idea arises, then the branch should not exclude it, but the BAP should not push to develop it at this time.
BAP staff commented that they were pleased with the report findings and with the review committee’s recommendations. Discussions are under way to strengthen interactions with the GCG Program as recommended by the review committee.
VII. PROGRAM HIGHLIGHTS
A. Is Alzheimer’s Disease a Neurovascular Disorder?
Dr. Berislav Zlokovic from the University of Rochester Medical Center summarized his group’s research on neurovascular mechanisms and targets in AD. Several diseases of the central nervous system may derive from a common mechanism of neurodegeneration resulting from disorders of the neurovascular unit, a hierarchal system of cerebral arteries, pial and intracerebral arteries, and brain capillaries, and from the dysfunction of the neurovascular membranes, the blood-brain barrier (BBB). These dysfunctions include errors in clearance of excitotoxins or protein aggregates, as well as impaired vascular competence, for example, impaired brain vascular repair.
Amyloid beta (Ab) is regulated in the central nervous system through a series of steps: (1) Ab production that is not altered in late onset AD; (2) influx and re-entry of soluble forms across the BBB via the RAGE protein, which could be increased in late onset AD; (3) clearance by transport across the BBB from the brain to the blood via the LRP1 protein, which is reduced in late onset AD; (4) binding to transport proteins such as apoE, apoJ, and a2M; (5) enzymatic degradation by proteins, astrocytes, and microglia; (6) slow removal through bulk flow from the interstitial fluid to the cerebrospinal fluid; (7) oligomerization and aggregation; (8) transport across the BBB and blood-cerebrospinal fluid barrier by megalin; and (9) binding to peripheral agents, such as soluble LRP1 and immunoglobulin G (IgG), which carries considerable therapeutic potential especially in early stages of AD.
Dr. Zlokovic discussed strategies to improve faulty clearance, vascular repair in the brain, cerebral blood flow, and neurovascular coupling. One such strategy is the increase of LRP, whose levels decrease in cells treated with Ab42. Treatment with statins and the blockade of the RAGE receptor increase LRP levels in Ab42-treated cells. Mice treated with soluble LRP fragments appear to learn at a faster rate and exhibit blood flow that is close to normal. Small-library screening also has been employed to identify compounds that impede the interaction between RAGE and Ab. This effort has yielded the MEOX2/Gax gene, which is expressed only in the adult vascular system and controls angiogenesis, cell migration, cell proliferation, and clearance. Mice carrying partial deletions of MEOX2 perform poorly on the Barnes maze and exhibit increased levels of endogenous Ab. Furthermore, the transduction of cells from patients with AD with human Gax restores LRP production. Examination of pial cerebral arteries from patients with AD has shown that two transcription factors, myocardin and serum response factor, are overexpressed in these arteries. Introduction of these factors into vascular smooth muscle cells results in significant reductions in blood flow, inability to respond to blood-flow regulation, and accumulation of endogenous Ab. Studies of the effects of apoE on Ab retention in the brain, as well as the effects of combined ApoE4 and LRP on angiogenesis, are under way.
B. The Role of Cardiovascular Risk Factors in Predicting Longevity
Dr. Dellara Terry of the Boston University School of Medicine discussed studies of centenarians and the genetic and environmental lifestyle factors involved in exceptional longevity. Studies of centenarians’ offspring showed lower mortality rates and lower prevalence of age-related diseases such as diabetes, heart disease, and hypertension. For those who do develop these diseases, the age of onset is delayed. Using extensive cardiovascular phenotypic data from the Framingham Heart Study, Dr. Terry and her colleagues followed a sample of 2,531 study participants (56 percent women) aged 40 to 50 years to identify predictors of survival and morbidity-free survival past age 85. A third of the sample lived to this age, and 22 percent survived free of morbidities (specified as myocardial infarct, coronary insufficiency, congestive heart failure, stroke, cancer, and moderate or severe dementia).
Female sex, lower blood pressure and total cholesterol, absence of glucose intolerance, nonsmoking status, and higher educational attainment predicted survival and morbidity-free survival. With each additional risk factor, the predicted probability of survival to age ≥85 years decreased: Males with no risk factors had a predicted probability of survival of 37 percent versus 2 percent for males with all five risk factors; females with no risk factors had a predicted probability of survival of 65 percent versus 14 percent for females with all five risk factors.
These findings are consistent with the World Health Organization Report on major contributors to global burden of disease. Although the presence of these risk factors in midlife had a dramatic effect on survival beyond age 85, all were modifiable except for education. Dr. Terry noted that the definition of diabetes was more stringent at the time this information was collected on the sample and that the uniform lethality of diabetes and left ventricular hypertrophy most likely has changed because of treatment improvements. On the basis of these studies, Dr. Terry concluded that screening for these risk factors should be done at an early age. Future studies will focus on the Framingham Heart Study Offspring Cohort and compare persons who had two parents that survived to age 85 with those who had one parent or no parents that survived to age 85.
Aging longitudinal cohorts offer opportunities for investigators to study, in a prospective fashion, the aging process and exceptional survival. However, because so few individuals survive to these exceptional end points, the study population is relatively homogenous. Work is under way to correlate phenotypes with genetics and with imaging studies. Data also have been collected regarding changes in fitness levels; whether these changes modify cardiovascular risk factors over time has not been examined. A Council member suggested that functional ability and active life expectancy be studied.
C. Newly Generated CD4 T cells in Aged Animals Do Not Exhibit Age-Related Defects in Response to Antigen
As people age, they exhibit increased morbidity and mortality from infectious diseases partly because of age-related declines in immune function. The ability to respond to vaccine also decreases. Dr. Laura Haynes from the Trudeau Institute in Saranac Lake, NY, summarized her studies on helper CD4 T cell function, the goal of which is to identify ways to improve vaccine efficacy for older persons. Helper CD4 T cells aid in directing humoral response by assisting B cells in producing antibodies. The interactions between helper T cells and B cells involve several factors, including cytokines and cell surface molecules. In response to vaccine, helper T cells stimulate the proliferation of B cells and their differentiation into plasma cells, which generate a large number of antibodies, or memory cells which can produce antibodies at a later time.
Dr. Haynes presented data from a T cell receptor transgenic mouse strain that is specific for pigeon cytochrome C (PCC) peptide. This mouse model provides a source of antigen-specific CD4 T cells which allow adoptive transfer experiments to be performed in order to compare cells obtained from young and old mice. The aged CD4 T cells exhibited reduced expansion and IL-2 production both in vitro and in vivo and went through fewer rounds of cell proliferation within a given period of time when compared to the young CD 4 T cells. Helper activity was also reduced for aged T cells in vivo, as shown by decreased expansion and differentiation of B cells in these animals. Immunohistochemistry revealed that both young and aged T cells migrated to the follicles, forming germinal centers, but that the germinal centers with aged T cells were more disorganized and less abundant than those produced in the young mice. Moreover, the aged CD4 T cells expressed less CD154 marker and fewer aged cells could be recovered seven days after immunization with a vaccine. Aged influenza-specific CD4 T cells produced less IgG, indicating that their ability to help the response to influenza was reduced greatly.
To determine why these defects occurred, Dr. Haynes and her colleagues studied CD4 T cells that were newly generated in both aged and young mice. New CD4 T cells from aged mice functioned similarly to those from young mice both in vitro and in vivo, as evidenced by similar rates of repopulation, expansion, and IL-2 production. In vivo, the aged thymus was less able to produce T cells, although the cells it did produce were able to expand and express IL-2 at rates similar to those in a younger thymus. These findings indicate that functional defects in naïve CD4 T cells from aged individuals most likely resulted from the amount of time these cells spent in the periphery. Dr. Haynes concluded by noting efforts that are under way to develop adjuvant therapies that improve T cell function in older individuals.
Dr. Dan Longo, Scientific Director, NIA, described the twice-yearly retrospective review process for the intramural program, resulting in each laboratory being reviewed once every four years. The Board of Scientific Counselors provides specific feedback and direction.
Laboratory of Epidemiology, Demography, and Biometry
Dr. Jack Guralnik discussed the Laboratory of Epidemiology, Demography, and Biometry (LEDB), which conducts research on aging and age-associated diseases and conditions using population-based epidemiologic and biometric methods. Laboratory staff work collaboratively both within and among four groups—the Epidemiology and Demography Section, the Neuroepidemiology Section, the Geriatric Epidemiology Section, and the Biometry Section—and with other NIA and outside investigators. The mission of the LEDB is to elucidate the etiology of diseases and conditions of old age, to study the aging process, and to develop evidence useful in developing and evaluating preventive procedures and public health practices. This research is done using epidemiologic studies of cohorts of older persons in several locations in the United States and abroad, and is further supported by combining epidemiologic data with information from other disciplines and by evaluating the consistency of epidemiologic data with etiologic hypotheses developed either clinically or experimentally. The research agenda emphasizes three important and interrelated areas: Physical function and disability, cognitive function and dementia, and age-associated diseases and conditions. LEDB research also addresses factors related to successful aging.
Several important longitudinal cohort studies that address specific areas of aging were developed by LEDB investigators in the 1990s. These studies have been highly productive in terms of research output and are still actively used for new research analyses. They include the Women’s Health and Aging Study, aimed at understanding the causes and course of physical disability in older women; the Honolulu-Asia Aging Study, a study of cognitive decline and dementia that has added a valuable brain autopsy component; the Health, Aging, and Body Composition Study, which has documented changes in body composition and biologic markers that influence functional outcomes in older whites and African Americans who were nondisabled when the study began; the Age, Gene/Environment Susceptibility Study in Reykjavik, Iceland, which has comprehensive evaluation of multiple body systems, including computed tomography and magnetic resonance imaging scans of the brain, heart, abdominal fat, liver, bone, and lower extremity muscle; and the InChianti Study in Italy, which is evaluating impairments in six physiologic domains that can influence the loss of ability to walk.
In addition to these observational studies, LEDB investigators are now involved in two major randomized clinical trials. The Lifestyle Interventions and Independence for Elders (LIFE) Study is a pilot clinical trial of exercise to prevent mobility disability. Investigators recently have finished evaluating participants for functional outcomes after a year of exercise or participation in a healthy aging educational program. In collaboration with the National Heart, Lung, and Blood Institute, LEDB conducts the cognitive substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD-MIND), a clinical trial of the effects of aggressively treating blood sugar elevations, high blood pressure, and lipid abnormalities in diabetics to examine the impact on cognitive decline. The LIFE Study has recently completed data collection and results should be published in 2006. The ACCORD-MIND Study will not be completed until 2009.
Laboratory of Molecular Gerontology
Dr. Vilhelm Bohr presented work that the Laboratory of Molecular Gerontology (LMG) has pursued on mechanisms that generate genomic instability in aging cells and lead to age-associated diseases. In normal cells, DNA repair plays an important role in preventing genomic instability by removing potentially mutagenic DNA lesions. To better understand aging and genomic instability, the LMB analyzes DNA repair pathways in DNA repair-proficient and DNA repair-deficient human and mouse cells and in wild type and knockout in vivo mouse model systems.
Werner and Cockayne syndromes are human diseases of interest because they are associated with symptoms of premature aging and defects in DNA repair, and can serve as models for research on aging. Werner and Cockayne syndromes involve defects in proteins that are members of the recQ family of helicases, also called the guardians of the genome, because of their ability to protect against genomic instability. Werner protein participates in DNA double strand break repair and base excision repair, which removes oxidative lesions from DNA. The molecular processes and protein interactions in which Werner protein participates are being studied in extracts of stressed and unstressed cells using biochemical and molecular genetic approaches. For example, the cellular distribution of Werner protein is being examined in cells treated with or without DNA damaging agents, allowing investigation of whether Werner protein co-localizes with DNA damage. Werner and some other premature aging proteins also participate in repair and maintenance of telomeres, which is another area of interest in LMG.
Age-associated DNA damage is more common in mitochondrial than in nuclear DNA, and the gradual loss of mitochondrial function may be a major factor in aging. This may at least in part reflect the fact that mitochondria appear to express a subset of the DNA repair pathways that protect nuclear DNA. Additional studies of mitochondrial DNA repair are needed to better understand its unique aspects and how it is coordinated via crosstalk with nuclear DNA repair.
LMG also is studying hypermutation and its role in generating antibody diversity. Recent studies suggest that hypermutation and DNA repair may require distinct but overlapping functions in mice and humans.
Dr. Bohr concluded his presentation by further discussing connections between mitochondria and telomeres. Telomerase function has been detected in mitochondria, and mitochondrial helicases can function at telomeres. In addition, DNA damage induced by oxidative stress in the mitochondria is targeted toward telomere DNA. It also is possible that apoptotic signaling goes from telomeres to mitochondria.
Increased understanding of the mechanisms underlying the increased genomic instability and mitochondrial dysfunction that is associated with the aging process is imperative in order to develop therapeutic strategies focused on lowering the incidence of age-associated disease and thereby improving the life quality in elderly people.
IX. 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).
The 97th meeting of the National Advisory Council on Aging was adjourned at 2:00 p.m. on February 1, 2006. The next meeting is scheduled for May 23–24, 2006.
I hereby certify that, to the best of my knowledge, the foregoing minutes and attachments are accurate and complete.3
Richard J. Hodes, M.D.
Chairman, National Advisory Council on Aging
Director, National Institute on Aging
Prepared by Miriam F. Kelty, Ph.D.
With assistance by Rose Li and Associates, Inc.
MEMBERSHIP ROSTER
NATIONAL ADVISORY COUNCIL ON AGING
NATIONAL INSTITUTE ON AGING
(Terms end December 31) (*WGoP Member)
Chairperson
Richard J. Hodes, M.D.
Director, National Institute on Aging
National Institutes of Health
Bethesda, MD
*Elizabeth H. Blackburn, Ph.D. (2006)
Professor
Dept of Biochemistry & Biophysics
University of California
San Francisco, CA
Melissa M. Brown, M.D., M.N., M.B.A. (2006)
Director
Center for Value-Based Medicine
Flourtown, PA
Kenneth V. Brummel-Smith, M.D. (2009)
Professor and Chair
Department of Geriatrics
Florida State University College of Medicine
Tallahassee, FL
*John T. Cacioppo, Ph.D. (2007)
Blake Distinguished Service Professor
Department of Psychology
Director, Center for Cognitive and Social Neuroscience
University of Chicago
Chicago, IL
Carl Eisdorfer, Ph.D., M.D. (2009)
Knight Professor and Director
Center on Aging
University of Miami
Miami, FL
*Linda P. Fried, M.D., MPH (2006)
Professor, Medicine, Epidemiology & Health Policy
Director, Division of Geriatric Medicine & Gerontology
Director, Center on Aging and Health
The Johns Hopkins Medical Institutions
Baltimore, MD
Lawrence M. Friedman, M.D. (2009)
Independent Consultant
11712 Farmland Drive
Rockville, MD
Mary Ganguli, M.D., M.P.H. (2009)
Professor of Psychiatry and Epidemiology
Department of Psychiatry
University of Pittsburgh
Western Psychiatry Institute & Clinic UPMC
Pittsburgh, PA
Alan M. Garber, M.D., Ph.D. (2007)
Director
Center for Primary Care and Outcomes Research
Center for Health Policy
Stanford University
Stanford, CA
Paul Greengard, Ph.D. (2008)
Vincent Astor Professor
Laboratory of Molecular & Cellular Neuroscience
The Rockefeller University
New York, NY
*Virginia M.-Y. Lee, Ph.D. (2007)
Professor
Dept of Pathology & Laboratory Medicine
Univ of Pennsylvania School of Medicine
Philadelphia, PA
Spero M. Manson, Ph.D. (2006)
Professor of Psychiatry and Head
American Indian & Alaska Native Programs
University of Colorado Health Sciences Ctr
Aurora, CO
Mills, Terry L., Ph.D. (2008)
Associate Dean for Minority Affairs and Special Programs
Office for Academic Support and Institutional Services
University of Florida
Gainesville, FL
John C. Morris, M.D. (2009)
Professor
Washington University School of Medicine
St. Louis, MO
Gary B. Ruvkun, Ph.D. (2007)
Professor, Molecular Biology
Massachusetts General Hospital
Boston, MA
Gerald P. Schatten, Ph.D. (2009)
Professor, Pittsburgh Development Center
Magee-Womens Research Institute
University of Pittsburgh
Pittsburgh, PA
Albert L. Siu, M.D., M.S.P.H. (2008)
Ellen and Howard C. Katz Professor
Chairman, Brookdale Department of Geriatrics and Adult Development
Mount Sinai School of Medicine
The Mount Sinai Medical Center
(and Director, Geriatric Research, Education, and Clinical Center, Bronx Veterans Administration)
New York, NY
*Mary E. Tinetti, M.D. (2008)
Gladys Phillips Crofoot Professor
Department of Internal Medicine, Epidemiology, and Public Health
Director, Program on Aging
Yale University School of Medicine
New Haven, CT
EX OFFICIO MEMBERS
Michael O. Leavitt
Secretary
Department of Health and Human Services
Hubert H. Humphrey Building
Washington, D.C.
Elias Zerhouni, M.D.
Director
National Institutes of Health
Public Health Service
Bethesda, Maryland
James F. Burris, M.D.
Chief Consultant
Geriatrics & Extended Care Strategic Healthcare Group
Department of Veterans Affairs
Washington, D.C.
Kenneth G. Pugh, M.D.
Commander, MC, U.S. Navy
Department of Medicine
National Naval Medical Center
Bethesda, MD
John Wren
Director, Center for Planning & Policy Development
U.S. Administration on Aging, DHHS
Washington, D.C.
1. 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.
2. 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.
3. These minutes will be approved formally by the Council at the next meeting on May 23-24, 2006, and corrections or notations will be stated in the minutes of that meeting.
