Council Minutes - May 2007

The 101st Meeting
May 15–16, 2007

CONTENTS

1. REVIEW OF APPLICATIONS
2. CALL TO ORDER
3. REPORT: Task Force on Minority Aging Research
4. REPORT: Working Group on Program
5. PRESENTATION: Peer Review Initiatives at CSR
6. PROGRAM HIGHLIGHTS
7. ADJOURNMENT
8. CERTIFICATION

Attachment A: Roster of the National Advisory Council on Aging
Attachment B: Director's Status Report

The 101st meeting of the National Advisory Council on Aging was convened on Tuesday, May 15, 2007, at 3:00 p.m. in Building 31, Conference Room 6, National Institutes of Health (NIH), Bethesda, Maryland. 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, May 15, from 3:00 p.m. to 5:00 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, May 16, from 8:00 a.m. to 1:30 p.m.

Council Participants:
Dr. John T. Cacioppo
Dr. Peggye Dilworth-Anderson
Dr. Carl Eisdorfer
Dr. Lawrence M. Friedman
Dr. Mary Ganguli
Dr. Alan M. Garber
Dr. S. Michal Jazwinski
Dr. Sundeep Khosla
Dr. Virginia M.-Y. Lee
Dr. Terry L. Mills
Dr. John C. Morris
Dr. Orien Reid
Dr. Gary B. Ruvkun
Dr. Gerald P. Schatten
Dr. Albert L. Siu
Dr. Mary E. Tinetti

Absent:
Dr. Ken Brummel-Smith
Dr. Paul Greengard

Ex-officio Participants:
Dr. James Burris, Department of Veterans Affairs
Dr. Kenneth Pugh, National Naval Medical Center

Absent Ex-officio Participants:
Mr. John Wren, Administration on Aging, U.S. Department of Health and Human Services (HHS)

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. Sato Ashida, National Human Genome Research Institute
Dr. Francois Boller, Center for Scientific Review, NIH
Dr. Sherry Dupere, Center for Scientific Review, NIH
Ms. Janet Gregory, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Dr. Jonathan W. King, Center for Scientific Review, NIH
Dr. Cheryl Kitt, Center for Scientific Review, NIH
Ms. Denise Manouelian, NIDDK
Dr. Nancy Miller, NIH/Office of the Director
Dr. Dana Plude, Center for Scientific Review, NIH
Dr. Peter T. Vlahos, General Services Administration

Members of the Public Present:
Dr. Laura Carstensen, Stanford University Center on Longevity
Ms. Cynthia Farrell, Alliance for Aging Research
Ms. Christy Gilmour, American Academy of Orthopaedic Surgeons
Ms. Chris Herman, National Association of Social Workers
Dr. Patricia Kobor, American Psychological Association
Dr. Rose Maria Li, Rose Li and Associates, Inc.
Ms. Frances McFarland Horne, Rose Li and Associates, Inc.
Mr. Daniel Perry, Alliance for Aging Research
Ms. Amy Pollick, Association for Psychological Science

I. 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).2

II. CALL TO ORDER

Dr. Hodes welcomed members to the open session of the 101st National Advisory Council on Aging meeting and called the meeting to order at 8:04 a.m. on Wednesday, May 16, 2007.

A. Announcements

Dr. Hodes announced that Ronald Kohanski, Ph.D., has been named Deputy Director of the Biology of Aging Program and that Rebecca Fuldner, Ph.D., has been named Chief, Aging Physiology Branch. Dr. Wen-Hsing Cheng, Health Scientist Administrator, has joined the Neuroscience and Neuropsychology of Aging (NNA) Program.

Dr. Hodes noted the contributions of two former members of the scientific community. Dr. Leon Thal, professor at the University of California San Diego Medical School and past Council member, who died in a plane crash in February, was recognized for his leadership in clinical and translation research on Alzheimer’s disease (AD), including the NIA-sponsored Clinical Trials Study Group. Dr. Hodes also noted the death of Dr. Stephen Straus, the first director of the National Center for Complementary and Alternative Medicine, who died of brain cancer on May 14.

Ms. Kathie Reed announced that the NIA strategic planning document, Living Long and Well in the 21st Century—Strategic Directions for Research on Aging, would be posted on the NIA Web site. The NIA plans to solicit input on this document from the wider research and advocacy community through June 30.

B. Director’s Status Report

Council members were reminded that in current dollars, the NIA budget had increased and leveled out, whereas in constant dollars, the budget had peaked in 2003 and experienced significant losses (-14.1 percent) in buying power since 2003. Success rates for grants remained constant from 1998 to 2003, with percentages in the high 20s. Since then, the success rates have dropped to about 18 percent. The success rate is projected to increase for FY2008 to 19 percent, but Dr. Hodes cautioned that success rates could increase because of fewer applications, which would be a cause for concern if this reflected discouragement by the research community. A budget increase was not proposed in the President’s FY2008 budget.

During FY2007, the NIH is committed to buttressing core areas of vulnerability, including the ability of new investigators to compete for support, and protecting investments in well-established investigators who have little or no other significant support. Funding for new investigators may require as much as a 10 percentile point differential, and a new grant program will offer 1-year bridging funds to give established investigators whose applications fail to make the Institute’s payline an opportunity to reapply.

Consistent with NIH policy to protect the number of competing research project awards that can be made during a time of flat budgets, non-competing research project grant (RPG) awards have been adjusted to provide no inflationary increases in FY2007. NIH policy for FY2008 under the President’s budget request again proposes no inflationary increase for direct recurring costs, although this might be reconsidered by NIH if the budget climate improves. In both the operating plans for FY2007 and under the FY2008 President’s budget, competing RPGs will be managed to an average award amount equal to FY2007 levels.

Dr. Hodes focused the rest of his presentation on the NIH Roadmap. He reminded the Council that the Roadmap is intended to serve as an incubator space for programs that, due to their cross-cutting relevance and/or complexity, warrant concerted attention from the NIH as a whole. The projects should be transforming, and their outcomes must be synergistic among many Institutes and Centers (ICs). Dr. Hodes also emphasized that these projects are funded by the NIH Common Fund for a limited amount of time, 5 to 10 years. The Common Fund is scheduled to reach its peak at 1.7 to 1.8 percent of the entire NIH budget and will not increase unless the NIH budget increases at a better than inflationary rate or unless otherwise determined by appropriations language.

To prepare for the transition of the first cohort of Roadmap initiatives out of the incubator space, the NIH has begun soliciting the next set of initiatives for funding consideration in FY2008­ and FY2009. New initiatives are developed through a series of scientific consultation meetings beginning in the summer and fall of 2006 involving scientists from academia and industry as well as public representations, NIH staff idea submissions, and Web-based public input/comment solicitations, and are approved by IC Directors. The areas currently under concept development fall into four categories: (1) major initiative areas, (2) pilot topics, (3) areas for coordination, and (4) emphasis/strategic planning areas.

Potential New Roadmap Initiative Areas

Major NIH Roadmap for Medical Research programs are broad coordinated funding initiatives designed to overcome grand challenges in biomedical/health research that do not naturally fall within the purview of one or just a few Institutes and Centers. These initiatives are selected based on their potential to have a transformative impact on the way science is conducted. The areas that were selected for consideration in the current planning cycle are:

• Human Microbiome - characterization of microbial flora coexisting with humans.
• The study of Inflammation as a common mechanism for disease.
• Human Phenome - Development of standardized and refined phenotyping tools as resources for systematically cataloging human phenotypes.
• Proteome and Protein Capture Tools - develop ent of high quality probes, such as antibodies and aptamers, for each protein existing in animal models and human cells.
• Epigenetics – systematic study of stable genetic modifications that are independent of changes in nucleic acid sequence and that result in changes in gene expression and function.

The decision was made to move forward with two of these areas, the Human Microbiome project, and Support for Epigenetics in FY2008. The proposed initiatives on Phenotyping and on Development of Proteome and Protein Capture Tools are currently being developed further for possible future implementation. The proposal on inflammation was not supported in large part because a review of ongoing NIH funding revealed that work on inflammation as a common mechanism of disease is currently receiving substantial financial support.

Potential Pilot Topics

These involve potentially important concepts that are not appropriate at this time for selection as major Roadmap initiatives. Proposals for these topics will be developed, with possible reconsideration in the future as Roadmap initiatives. These include:

• Connectivity map, or gene expression profiles that describe how perturbation of a particular pathway affects the entire genome.
• Transient molecular complexes or the methods to study them.

Potential Areas for Coordination

These are areas where additional information is needed regarding the current research portfolio and previous and ongoing efforts to coordinate activities in these areas. Roadmap coordination groups will assess current efforts and, if necessary, propose activities to foster collaborations across organ systems or disease areas. These topics include:

• Regenerative medicine.
• Pharmacogenomics.
• Bioinformatics.

Roadmap Emphasis/Strategic Planning Areas

These are areas where the breadth and complexity of issues highlighted through the Roadmap process will require coordinated planning with existing groups. These areas include:

• Training and careers. The NIH will collaborate with academic institutions and scientific societies to define, develop, and foster the optimal scientific workforce.
• Health disparities. The National Center on Minority Health and Health Disparities (NCMHD) leads the NIH in strategic planning and coordination of research funding in this area. Roadmap strategic planning would determine whether added value could be derived from further analysis of the current NIH portfolio to determine gaps and ways to promote coordination of activities in this area.
• Science of science administration. This would involve an attempt to determine the most effective administrative approaches for achieving programmatic goals, including efforts to examine the most effective use of multiple mechanisms and consider possible requirements for new administrative strategies for review and funding, with programmatic goals such as high innovation, support of junior investigators, and productive research teams being the targets for new approaches.

Dr. Hodes outlined several next steps in the Roadmap process leading to the anticipated selection of new Roadmap initiatives by the NIH Director in the summer or fall of 2007. The pool for Roadmap initiatives is about $500 million. Assuming projects occupy incubator space for up to 10 years, this suggests a turnover of about $50 million per year. The NIH leadership does not currently intend to undertake this process of full solicitation of new Roadmap initiatives every year. Instead, it is expected that a cohort will be developed for FY2008 and candidates identified for further development in FY2009.

In response to Council members’ expressed enthusiasm for allowing grant applications to compete among all Roadmap initiatives rather than pre-set the number to be funded, Dr. Hodes stated that although initial sums might be set aside for each initiative, requests for applications (RFAs) can be monitored to adjust funding levels depending on the quality of submissions.

C. Future Meeting Dates

September 25–26, 2007 (Tuesday and Wednesday)
January 29–30, 2008 (Tuesday and Wednesday)
May 20–21, 2008 (Tuesday and Wednesday)
September 24–25, 2008 (Wednesday and Thursday)
January 27–28, 2009 (Tuesday and Wednesday)
May 19–20, 2009 (Tuesday and Wednesday)
September 22–23, 2009 (Tuesday and Wednesday)

C. Consideration of the Minutes of the Last Meeting

The minutes of the January 2007 meeting were considered. A motion was made, seconded, and passed to approve the minutes.

III. REPORT: Task Force on Minority Aging Research

Dr. Terry Mills reported on the previous day’s task force meeting, where Dr. Andrew Monjan, Chief of the Neurobiology of Aging Branch of the Neuroscience and Neuropsychology of Aging (NNA) Program, gave a presentation on sleep among African Americans. Consequences of disordered sleep include attention and memory problems, excessive daytime sleepiness, depressed mood, nighttime falls, overuse of hypnotic drugs and over-the-counter medications, possible adverse interactions with comorbid conditions, lowered quality of life, and metabolic dysfunction. Several sleep studies covering a broad range of minority groups have been conducted, including the San Diego Sleep Study (Girardin et al., Biol Psychiatry 2000;47:921–7), the CARDIA Sleep Study (Lauderdale et al., Am J Epidemiol 2006;164:5–16), and the Race and Sleep study (Ancoli-Israel et al., Chest 2002;122:1148–55). A large number of published reports suggest that older African Americans have poorer sleep than do comparable Caucasians and may be at greater risk for sleep disordered breathing.

Dr. Mills then reported on a National Center on Minority Health and Health Disparities (NCHMD)-sponsored conference to further explore minority health disparities. Dr. J. Taylor Harden welcomed names of individuals from community-based organizations who should be invited to participate in the conference. NIA is developing a Web-based toolkit, which will provide investigators and the public with information about issues related to the recruitment and retention of minority subjects in health research. The toolkit will consist of two components: best practices and barriers. It also will provide links to Research Centers for Minority Aging Research/Alzheimer’s Disease Center satellites, NIA-supported publications, Institute of Medicine/National Academies reports commissioned by the NIA, and Method to Extend Research in Time grantees. NIA is working to provide Web-based content that is of sufficient depth for established scholars but broad enough not to discourage emerging scholars.

Dr. Mills also discussed efforts to promote research careers in aging and health disparities through a K01 mechanism (http://grants2.nih.gov/grants/guide/rfa-files/RFA-AG-06-008.html). The task force expressed concern and disappointment because only three applications had been received in response to this RFA, all in the behavioral and social sciences, and none had been deemed sufficiently meritorious for funding. Task force members discussed the composition of the review panel, noting that many reviewers did not have backgrounds in behavioral and social sciences. To extend the pool of potential reviewers, Drs. Mills and Harden developed a list of 50 candidates who are experienced in health disparities research and represent a wide range of expertise and NIH experience in research, mentoring, and training. Task force members were invited to recommend additional names.

The Office of Behavioral and Social Science Research has put forward a funding opportunity announcement (FOA) on understanding and reducing health disparities. Several ICs and the Centers for Disease Control and Prevention have joined to support this FOA, which will use the R01 and R21 mechanisms. Dr. Robin Barr clarified that with the move toward electronic submission of applications, the NIH is developing new language, and FOA is the new term for program announcements.

Dr. Mills concluded his report by noting the following dates:

Discussion focused on the K01 devoted to promoting research careers in aging and health disparities. Dr. Mary Tinetti acknowledged the need to broaden the areas of expertise on the review committees but wondered how this need could be balanced with a focus on scientific rigor. Dr. Mills emphasized that the task force respected the peer review process and the importance of scientific rigor, but members also wanted to increase sensitivity about the need for appropriate subject matter expertise. Dr. Albert Siu considered several of the reviewers to be thoughtful, with a history of mentoring and sensitivity to minority aging research. Nevertheless, there was concern that the lack of behavioral scientists on the review panel might have disadvantaged applicants. Noting the small number of applications, Dr. Barr suggested that the NIA and the Council consider ways to increase the response to this program.

IV. REPORT: Working Group on Program

Dr. John Morris reported on several issues discussed during the previous day’s closed session.

A. Advisory Meetings

Four advisory meetings were discussed by the working group.

Aging in Sub-Saharan Africa

Dr. Richard Suzman, Director of the Behavioral and Social Research (BSR) Program, provided the working group with information about a conference addressing cross-national research on aging in sub-Saharan Africa. A workshop report, which BSR had commissioned the National Academies to prepare, listed nine recommendations to obtain basic aging data that would allow for the implementation of technical assistance and other activities. Dr. Suzman will take these recommendations under advisement according to BSR’s ability to fund them.

BIOCARD

Dr. Neil Buckholtz from the NNA Program reported on Biomarkers for Older Controls at Risk of Dementia (BIOCARD). This study was initiated in 1995 by the National Institute on Mental Health (NIMH) to assess middle-aged, normal individuals who were first-degree relatives of persons with dementia. The study involved annual cognitive evaluations and a full biomarker screen, including cerebrospinal fluid (CSF) analysis and structural neuroimaging by magnetic resonance imaging (MRI), every 3 years. The study had been placed on hold in 2005 because of a change in investigators and other issues. To assess the current and potential value of the BIOCARD Study, a small advisory group was convened and recommended that the NIA and NIMH assess the data and tissue that have been collected, determine whether the remaining participants enrolled since 1995 would be willing to continue participating in the study, and on the basis of this information assess the value of funding a study to follow up the cognitive outcomes of these participants.

Dr. Morris reported that the Working Group on Program endorsed the advisory group’s recommendations and supported the plan of both Institutes to first evaluate the quality and status of the data and tissue, and then develop specific recommendations.

In response to questions from Dr. Virginia Lee, Dr. Morris noted that the average age of the participants had been 55 years when the study began and would be approximately 65 years now. The age range was not known. The cohort had begun with about 500 participants; of those approximately 350 were available to continue in the study. Dr. Morris also noted that these participants had been committed to the study.

Dr. Gerald Schatten encouraged the NIA to identify a new leader and leadership structure for the study. Dr. Morris responded that if the data are deemed useful and participants are willing to continue in the study, the NIA and NIMH would issue a call for applications to study this population. Dr. Hodes noted the consensus among Council members to make an initial assessment but asked whether the Council would support approval of a solicitation for further study contingent on the evaluation. Dr. Buckholtz reported that the NIMH was in the process of taking a physical inventory of samples, which are housed in a cryogenic facility in Frederick, Maryland, and that the Institutes were evaluating the status of various databases for clinical and cognitive information. At the same time, the Institutes were developing a letter to potential participants. In addition, institutional review boards would have to be contacted and consent re-given by participants.

On the basis of this information, the Council agreed to defer the full motion for consideration until more information is received about the status and quality of the data. Dr. Buckholtz will report to the Council on the evaluation at the September 2007 meeting, at which time the Council will entertain the full motion.

Cognitive Aging

Dr. Molly Wagster of NNA is planning a Cognitive Aging Summit, to be held October 10–12, 2007 in the Washington, DC, area. This will be an advisory meeting cosponsored by the McKnight Brain Research Foundation to help raise awareness about cognitive aging, assess the status of cognitive aging research, and seek to improve outcomes for cognitive aging in society through pharmacologic and behavioral intervention. Dr. Morris reported that this conference was unanimously approved by the Working Group on Program. A motion was made, seconded, and passed to approve the Cognitive Aging Summit.

Genetics of AD

Dr. Marilyn Miller of NNA proposed a Conference on the Genetics of AD: Where Do We Go from Here? A 2002 workshop on the same topic led to a successful genetics initiative for late-onset AD. Dr. Miller provided the working group with an update and proposed this conference to identify next steps in genetic research and epidemiology. The conference is planned for fall/winter 2007. Dr. Morris reported that the working group gave unanimous approval for this conference. A motion to approve the Conference on the Genetics of AD was seconded and unanimously passed by the Council.

B. RFA Concept Clearances

Dr. Morris reported on four proposed RFAs that were presented to the Working Group on Program, all of which were subsequently approved unanimously by the Council.

Menopausal Symptoms

Dr. Sherry Sherman from the Geriatrics and Clinical Gerontology (GCG) Program presented a proposed RFA for research on interventions to treat menopausal symptoms. She noted the many disorders accompanying menopause and the menopausal transition and the lack of data for effective management or treatment. The RFA, cosponsored by the National Institute of Child Health and Human Development (NICHD), would support work to develop more consistent assessment of disorders, as well as greater understanding about the range of interventions or therapies to be studied and use the U01 cooperative agreement mechanism.

Dr. Morris reported that the working group had discussed the advisability of continuing to set aside funds in this time of tight budgets. The working group also was concerned that the NIA would disproportionately support the proposed RFA, with relatively little support from other ICs or foundations. Dr. Morris noted that the working group had approved the RFA concept, with two dissenting votes.

In response to the working group’s concerns, Dr. Hodes remarked that the NIA takes seriously the tension between solicited and investigator-initiated research. For this particular RFA, the NIA will commit $3 million, the NICHD will commit $1 million, and other ICs are expected to commit smaller amounts. Dr. Hodes added that the NIA seeks to maximize cofunding, and he noted that the NIA supports a wide spectrum of RFAs, with greater funding commitment levels generally associated with perceived program relevance and recognized leadership in particular areas.

Dr. Siu suggested a standardized format for the presentation of RFA concept clearances by staff that would include a section on why an RFA is necessary. Dr. Hodes agreed to make this process more uniform.

Dr. Lee asked about the criteria used to determine whether an RFA is needed. Dr. Barr responded that the reasons for developing an RFA can differ. He cited as examples the identification of a new priority area and the acknowledgment that an activity can occur only through a mechanism or structure not addressed by investigator-initiated awards. For this particular RFA, Dr. Sundeep Khosla explained that the problem of managing menopausal symptoms has been poorly studied and that the RFA was attractive because it would provide a mechanism to promote much needed consistency in study criteria and outcome measures. Otherwise, he stated, this research area would continue to consist of primarily small studies that are difficult to generalize. Dr. Schatten agreed, adding that the RFA would facilitate careful study and provide more definitive data about methods for alleviating menopausal symptoms and the risk-benefit trade-offs.

Although Dr. Gary Ruvkun did not disapprove, he argued for general restraint in RFAs given the lack of available resources at this time.

Dominant Inherited AD

Dr. Buckholtz presented a proposed RFA to develop international resources for the identification, evaluation, and follow-up of families with dominant inherited AD. Although these individuals are few in number, he provided examples of the ways their participation in research can be powerful in identifying the underlying changes in carriers versus noncarriers—changes that might be apparent before symptoms start to appear. The idea for this RFA arose from a conference on AD held in October 2006, where there was strong support for developing a consortium of investigators to identify, recruit, and follow individuals with state-of-the-art assessment protocols. Under the U01 cooperative agreement mechanism, NNA would provide significant input to ensure the research was carried out with uniform methods that were easily understood by all investigators. The RFA would cost approximately $3 million in each of 6 years; funding for the first year would come from the NIA Director’s Reserve for FY2008. Dr. Morris reported that the Working Group on Program had approved this RFA unanimously.

Juvenile Protective Factors

Dr. Chhanda Dutta presented a proposed RFA to identify juvenile protective factors and their effects on aging. Her presentation to the working group discussed maturation and postnatal developmental events that might influence aging and lead to strategies to prevent age-related diseases. This RFA would solicit R01 applications with 3-year project periods. The NIA and NICHD would each commit $1.1 million to this RFA in FY2008.

Dr. Michal Jazwinski observed that RFAs tend to come to fruition after 2 or more years of discussion among exploratory advisory working groups and program staff. Council members are often asked to approve these RFAs without knowing the history behind them. Dr. Jazwinski suggested that RFA clearance requests to the Council include a brief recapitulation of events leading up to the RFA proposal.

With regard to the specific RFA proposal, Dr. Jazwinski questioned whether researchers would be able to distinguish between simple age changes and protective mechanisms that can be transplanted to older individuals. He noted the many compensatory mechanisms in older organisms and observed that the introduction of mechanisms from younger individuals might not work. Dr. Evan Hadley, Director of the GCG Program, responded that the RFA would address the issue of whether manipulating potential protective factors would produce deleterious results.

Other Council members expressed concern about the limitation of the RFA to postnatal factors. These members pointed out that investigators studying model organisms such as Caenorhabditis elegans or yeast or amniotic stem cells would be excluded. Dr. Hadley responded that this issue had been considered and that both prenatal and postnatal events were important. However, the dearth of information is much greater for postnatal events than for prenatal events.

Health Promotion for Older Workers

C. Other Issues

Dr. Schatten reported that during the previous year, the Alliance for Aging Research (AAR) spoke to the Council about its role in education and consensus building and its broad directions in aging research. Since then, Council members have talked with AAR Director Daniel Perry about ways the AAR could complement the NIA mission. Mr. Perry added that the Alliance is chairing an umbrella entity called Friends of the NIA, which comprises more than 50 national organizations. This entity offers an important voice and has submitted testimony to Congress. Mr. Perry also noted that Ms. Cynthia Farrell, AAR Director of Government Relations, has recently presented testimony to the Labor-HHS Subcommittee. He reported on further plans for presentations on Capitol Hill and expressed the Alliance’s desire to ensure that the importance of aging research is recognized.

Dr. John Cacioppo reported on a discussion he led on the review of T32 training grant applications. This discussion stemmed from a perception that the expertise on the single panel reviewing these applications lags behind recent growth in the BSR program. Dr. Cacioppo acknowledged Dr. Suzman’s effectiveness in recruiting T32 applications reflecting BSR advances in science, but he noted that the review committee is still focused on traditional gerontology issues, making it difficult for the newer, more innovative applications to receive adequate review. This in turn would hamper the development of new fields. In response to suggestions from the Scientific Review Office, the Council requested information on whether the percentages of T32s approved for funding differ across NIA programs.

A motion to approve a request from BSR to change the date for program review from January 2008 to September 2008 was made, seconded, and unanimously passed by the Council.

D.Statement of Understanding

The Statement of Understanding between the National Advisory Council on Aging and the NIA concerns routine activities and procedures that may be conducted without Council review and clearance. The Statement needs to be reconsidered annually at a Council meeting and re-approved or modified via a Council motion in the open session of Council.

V. PRESENTATION: Peer Review Initiatives at CSR

Dr. Cheryl Kitt, Deputy Director, Center for Scientific Review (CSR), reported on current major initiatives to recruit and retain the best reviewers and improve the identification of significant, innovative, and high-impact research. CSR reviews about two-thirds of grant applications submitted to the NIH. During the past year, 80,000 applications (double the number in 1998) were submitted and 57,000 were reviewed by CSR. Most of these applications are unsolicited, and the majority of them are R01s. The number of applications per applicant has increased during the past 5 years from 1.2 to 1.4, which translates to approximately 10,000 to 12,000 new applications coming in for review. During the past year, there were 18,000 reviewers, but average reviewer workload has decreased from 11.6 applications a decade ago to 6 last year. Dr. Kitt pointed out that reviewers are refusing to take more applications and are submitting more applications themselves. This development, along with the increased scientific breadth of applications, can increase the size of a review committee dramatically. In 2007 so far, CSR has involved 10,000 reviewers over two rounds of review. Although the charter members on a study section number about 18 to 20, the number can easily double depending on the review. Standing charter members number about 3,000, but the number of ad hoc reviewers has swelled.

Shorten the review cycle, especially for new investigators

Whereas the usual R01 application review cycle takes 9 months, a CSR pilot program aims to provide applicants with a review and score within 3 months so they can reapply with a revised application by the next submission deadline, 4 months earlier than usual. This includes new investigator summary statements within 10 days (compared to 30 days for all summary statements). A CSR evaluation found that the shortened review cycle appears to benefit new investigators in terms of expediting funding. The CSR aims to have reviewed more than 12,000 applications from new investigators by November 2007 and expects to implement expedited review cycles more widely.

Immediately assign applications to integrated review groups (IRGs)

CSR has retooled for electronic submission and is piloting assigning applications using text fingerprinting and artificial intelligence software. Fifty percent of principal investigators request a scientific review group, and CSR normally honors these requests. In another pilot supported by the governing structures of the NIH, CSR has used knowledge management software and machine-learning algorithms to text-mine cover letters. IRG assignments in the pilot initiative are in agreement 82 percent of the time with expert referrals. Referrals by experts will continue for difficult cases, and decision support algorithms will be used to assist human experts. Full implementation of this process will occur once a link from the NIH Electronic Research Administration is available.

Realign study sections

An internal review of all 23 IRGs will occur every 2 years, with one IRG reviewed per month, to assess fluctuations in science (i.e., changes in number of applications and needed scientific expertise). In addition, study sections will be redesigned with community or Peer Review Advisory Committee input. This effort has resulted in seven new or reorganized study sections, including new study sections in molecular neurogenetics and neurotechnology. The CSR also has planned six open-house workshops, or town hall meetings, to occur every other month through December 2007. These meetings are co-chaired by one study section Chair and one professional society Chair. Participants are asked about the most important questions or enabling technology they see for their areas of expertise within the next 10 years. They also are asked whether their field, in its present state, is appropriately evaluated within the current study section structure. The first workshop, which was focused on neuroscience, occurred in March and identified several scientific areas the community felt were not adequately addressed by existing study sections. The second open house was held in April and focused on behavioral and social science IRGs, and the next one, to be held at the end of June, will focus on disease-based IRGs.

Implement electronic reviews

CSR is implementing electronic reviews through telephone, video electronic discussion (VED), or asynchronous electronic discussion via the Web (AED). About 7 percent of applications have been reviewed in this manner; about 5,000 applications are anticipated to be reviewed in this way by December 2007. CSR projects that 20 percent of applications will be reviewed electronically in 2008, if resources permit.

Dr. Kitt briefly demonstrated VED, in which reviewers are provided with cameras, training, software, and telephone backup. VED occurs on a secure network. She also showed pictures of AED, which involves a threaded Web message board on which comments are posted within a 3-day window, and comments are available for all reviewers to see.

Dr. Kitt closed this segment of her presentation by reporting on the goals of NIH and CSR to streamline 50 percent of R01 applications. Efforts to streamline F32s are also under way, with a goal to streamline 40 percent. She reiterated the goal of having 10 percent of applications reviewed electronically.

Shorten the length of applications

CSR issued a request for information about application size and received more than 5,000 responses. About three-fourths of respondents called for shorter applications. Dr. Kitt highlighted the following findings:

• The majority of respondents felt that a shorter application would have no effect on their ability to present scientific ideas, although 30 percent believed they would be less able to present scientific ideas adequately.
• Sixty percent of respondents felt a shorter application would take less time to prepare, and equal percentages of respondents felt it would take the same amount of time or longer.
• Equal percentages of respondents said their ability to judge scientific merit would be the same or worse with a shorter application. Twenty-four percent felt a shorter application would improve their ability to judge scientific merit.
• Almost half of the respondents said a shorter application would increase their willingness to review.
• Sixty-five percent of respondents felt that review criteria should be changed to accommodate shorter applications.
• Almost half of the respondents felt there would be no disadvantage to specific groups if the application were shortened, but 27 percent of respondents thought that new principal investigators would be disadvantaged.
• Clinical research plans may require more application space so there may be instances when shorter applications will not be advisable.

Dr. Kitt pointed out operational and cultural advantages of shorter applications, including the ability of each reviewer to read more applications, smaller study sections, the ability to recruit more experienced reviewers, and a greater focus on impact and innovation and less on approach and preliminary results.

Other initiatives

Dr. Kitt considered the use of electronic review modes, shorter meetings, and shorter applications to be near-term solutions for recruiting and retaining the best reviewers. Other longer term plans include:

• Abolition of submission deadlines. Reviewers currently are allowed 2 weeks beyond a submission deadline, and there are six deadlines per year. In addition, about 40 percent of applications from reviewers go to special emphasis panels. CSR proposes to have an ongoing submission process so reviewers do not feel pressured to leave study panels to revise or resubmit applications. CSR also proposes to abolish submission deadlines for small business grants and fellowships. These proposals are still under discussion.
• Editorial board reviews. In this process, grant applications would come in for a general review and then be assigned to specific scientific groups. Pilots are under discussion for research grants and small business grants, and a skeletal operational plan has been devised for nondiversity F31s and F32s.

Dr. Kitt concluded that although a brand new review system is not necessary, CSR is enacting enhancements to ensure recruitment and retention of the best and brightest to review research.

Dr. Ganguli appreciated CSR’s efforts but raised concerns about overburdened reviewers and the challenges associated with monitoring and maintaining the quality of reviews. She speculated that electronic reviews would exacerbate this concern since the review committee would have limited personal interactions, including with program staff who convey funding priorities and RFA objectives. Dr. Kitt clarified that reviewers are responsible for understanding the type of funding mechanism they are reviewing, and should notify their Scientific Review Administrator (SRA) in advance if they believe that an application falls outside their area of expertise. She considered SRAs to be doing a good job of educating reviewers about applications. She added that SRAs are very anxious about the quality and appropriateness of their reviews. CSR also has a best practices committee that monitors the processing of summary statements, attends meetings, and reviews reviewer rosters.

Dr. Ruvkun noted a common perception that the quality of reviewers has declined. Dr. Lee observed that because there are so many reviewers and because so many senior investigators are unwilling to review, more reviewers are junior investigators who are not at the same level of sophistication as senior investigators. Thus they tend to evaluate applications based on the methods and experiments proposed rather than on the significance of the applications. Dr. Tinetti noted that most study sections are overwhelmed by the number of ad hoc reviewers who are overly focused on minutiae.

Dr. Kitt acknowledged challenges in recruiting senior investigators and mentioned that CSR has formed an internal community relations committee to address complaints received by applicants about review. She stated that often ad hoc reviewers are brought in for one application but can vote on all applications. CSR would like members who serve on a study section to have a greater breadth of expertise and for SRAs to limit the number of ad hocreviewers on a study section. She added that this was a cultural issue but acknowledged that CSR was reaching a “boiling point” as far as the size of a study section that can carry out an effective review.

Dr. Ruvkun believed that more pressure should be exerted on senior investigators to serve on study sections. He suggested that the National Academies be persuaded to issue an edict for service on a study section and that IC Directors call personally on R01 investigators with 20 or 25 years of funding. Dr. Kitt noted that CSR asks professional societies to provide a list of potential study section members and despite heroic efforts by SRAs, some senior investigators simply refuse to serve.

As one who has served on study sections, Dr. Khosla raised the issue of variance in scoring patterns. He speculated that this would become an even greater problem with more ad hocreviewers and more electronic reviews. Dr. Kitt acknowledged issues associated with scoring, including that some reviewers increase scores for applications they have seen before. However, she pointed out that the use of percentiles was an equalizer and that advisory councils serve as a second line of review.

Dr. Schatten suggested adding a box to the application face page where applicants could indicate their preferred study section and IC. He favored bringing in junior investigators as ad hoc reviewers to teach them how the system works. Dr. Kitt agreed and acknowledged the delicate balance needed for true peer review.

Dr. Cacioppo applauded the emphasis on innovation and impact, but he expressed concern that reviewers are not as focused during an electronic review as they are at a face-to-face meeting. This issue is of particular concern for complicated or innovative grants that require focused discussion. He asked whether CSR had analyzed potential special risks associated with electronic reviews. Dr. Kitt responded that NIH has experimented with review formats and opportunities and that CSR would conduct several pilot studies to test different application sizes within the next year.

Dr. Carl Eisdorfer asked about risk management, particularly the costs to a young investigator from resubmitting too quickly, from reviewers who cannot distinguish best from almost best, or from inappropriate review assignments. Dr. Kitt responded that some of these risks will be addressed during the evaluation component of the pilot initiatives and should not prevent CSR from attempting to streamline the process.

VI. PROGRAM HIGHLIGHTS

A. Geriatrics and Clinical Gerontology: Health Care for Older Persons with Chronic Illnesses

In his presentation, Dr. Albert Siu (Mount Sinai School of Medicine and a Council member) (1) illustrated the failings of the health care system for older persons with chronic illness, (2) reviewed models of geriatric care that have been demonstrated to be effective but have had limited adoption, and (3) indicated the need for research to update the technology of geriatrics care.

In the 40 years since the enactment of Medicare, much has changed in American medicine with respect to population demographics, epidemiology of illness, medical care, and payment. In contrast, much less has changed in the basic structure of health care delivery. Hospitals remain the dominant mode of acute care in any given community, and the face-to-face visit with a physician remains the dominant mode of ambulatory care. Changes are needed to respond to the needs of the growing number of older persons with chronic illnesses. Using hip fractures as a disease model, Dr. Siu has led a series of projects involving a consortium of hospitals to examine issues in health care delivery and the extent to which outcomes can be improved.

In Dr. Siu’s studies, about 40 percent of patients hospitalized for hip fractures experience complications. Routines, protocols, and the bed-centered environment within hospitals lead many patients to experience long periods of reduced mobility; only 35 percent are able to have surgery within 24 hours because of problems with operating room or surgeon availability or because of wait periods for consultation. Dr. Siu’s studies have shown that improved nonsurgical care (surgical timing, mobility, pain management, and early rehabilitation) is associated with improved survival and mobility 6 months after hip fracture. However, following discharge, most patients receive highly fragmented care with high rates of readmission.

Much of the ambulatory care for chronic disease takes place outside the clinic, but the face-to-face visit remains the mainstay of care because that is what Medicare will cover. Dr. Siu’s group examined doctors’ logs of their non-face-to-face interactions and discovered that for every 30 minutes spent with patients in the office, 18.7 minutes are spent in clinical interactions outside the office on nonreimbursable but necessary care, including coordinating care, counseling family members, managing medications, and responding to acute problems.

Dr. Siu then discussed a number of different models that have been developed and studied over the last two decades to improve the care of the elderly. Most of these interventions have resulted in small to moderate improvements in health and other outcomes but adoption of them has been limited to academic institutions, in Acute Care for Elderly or Geriatrics Evaluation and Management units. Implementation of these interventions generally requires considerable organizational and culture change in the parent health care organization. Without external incentives of significant cost savings, further diffusion of these models of improved care may be limited. He suggested that there is a need to update the model of geriatrics practice with new models that focus on cost savings in addition to improved patient and caregiver outcomes and satisfaction. He pointed to the field of palliative care to illustrate the possibility of developing programs with no external pressures or incentives. At the Mount Sinai Medical Center where
Dr. Siu and his colleagues conduct their research, they were able to show how much money would be saved per day, per admission, in terms of laboratory costs with the use of palliative care interventions. Aside from cost savings, these programs have been effective in decreasing pain and other distressing symptoms at the end of life, improving caregivers’ stress and satisfaction, as well as improving technical support to other hospitals interested in developing palliative care programs.

Dr. Siu also suggested a need to streamline the technology of geriatrics assessment by the use of item response theory to construct measures that could be used for computer-adapted testing, which could reduce the amount of time and the burden associated with collecting information on function and other aspects of health.

In the case of hip fracture, an analysis of self-report and performance measures from a sample of patients indicated an excellent degree of reliability throughout a range of functions. However, specific items were identified that were more informative at different points in that range. Thus, item-response theory and computer-adapted testing can help assessors determine where best to get information about patients’ ability to function as opposed to asking all patients all questions.

In discussion, Dr. Tinetti mentioned that the problem with many geriatric care models is not that they are not cost-effective but that the costs in hospitals are offset by the costs of home care. She noted the challenge of addressing cost-effectiveness when the entity that gets paid is not the entity that saves money. Dr. Siu agreed, pointing out that hospitals would not pay upfront costs for effective post-acute care models when Medicare would receive the savings benefit. He called for an integration of costs across the various segments of Medicare and the creation of a new payment system for geriatrics based on the home model or some version of the Program of All Inclusive Care for the Elderly. Dr. Eisdorfer noted the problem of disruption in the payment system. A large percentage of patients wait for discharge into a nursing home, but the state controls the number of nursing homes, and the hospital incurs thousands of dollars per day for those patients awaiting placement.

B. Behavioral and Social Research: Shifting Temporal Horizons Influence Motivation across Adulthood

Dr. Laura Carstensen (Stanford Center on Longevity) spoke about how the subjective sense of future time plays an essential role in human motivation and how sense affects choices, goals, and what is remembered. She discussed Socioemotional Selectivity Theory (SST), which maintains that two broad categories of goals shift in importance as a function of perceived time—those concerning the acquisition of knowledge and those concerning the regulation of emotional states. When time is perceived as open-ended, goals that become most highly prioritized are most likely to be those that are preparatory, focused on gathering information, on experiencing novelty, and on expanding breadth of knowledge. When time is perceived as constrained, the most salient goals will be those that can be realized in the short term, sometimes in their very pursuit. SST predicts that people of different ages prioritize different types of goals. As people age and increasingly perceive time as finite, they attach less importance to goals that expand their horizons and greater importance to goals from which they derive emotional meaning. Importantly, according to SST, such differences are not due to age per se but to differences in the perception of future time. Findings from a number of experiments support this key postulate, as well as studies of naturalistic occurrences that affect time horizons.

In testing postulates derived from SST, Dr. Carstensen and her colleagues documented a preference with increasing age for emotionally positive information in attention and memory. Theoretically, attending to positive information and remembering positive events contribute to emotional well-being. This “positivity effect” describes the developmental pattern that has emerged in which a selective focus on negative stimuli in youth shifts to a relatively stronger focus on positive information in old age. Numerous laboratories have now replicated the effect.

Recently, Dr. Carstensen’s team began to explore the potential downside to a preference for positive information in the area of decision making. Almost by definition, the decision process is emotionally taxing because choices generally involve some risk and often require the processing of unpleasant information. One study led by Dr. Corinna Löckenhoff examined age differences in information acquisition and recall while making health-related decisions. Using computer-based decision scenarios, both older and young adults reviewed choice criteria that contained positive, negative, and neutral information about physicians and health care plans. As predicted, older adults reviewed and recalled a greater proportion of positive as compared to negative information. Younger adults reviewed positive and negative information equally. Age differences were eliminated when motivational manipulations elicited information-gathering goals or when time perspective was controlled statistically.

In another study led by Dr. Greg Larkin, event-related functional MRI was used to determine whether younger and older adults differed in both self-reported and neural responsiveness to anticipated monetary gains and losses. The study provides evidence for intact striatal and insular activation during gain anticipation with age but shows a relative reduction in activation during loss anticipation. These findings suggest that there is an asymmetry in the processing of gains and losses in older adults that may have implications for decision making.

In sum, SST suggests that many differences between younger and older people that have long been believed to reflect intractable age differences in attitudes or the consequences of age-related decline may be neither. When people perceive time as finite, they attach greater importance to finding emotional meaning and satisfaction from life and invest fewer resources into gathering information and expanding horizons. Hypotheses generated by SST have led to discoveries of differential decline in the processing of certain types of information, pointed to areas of preserved function and growth into advanced age, and importantly, suggested ways to eliminate age differences when desired.

In discussion, Dr. Ganguli pointed out that Dr. Carstensen had shown cross-sectional data and wondered whether longitudinal data might show differences because more negative-focused people have died. She also asked whether Dr. Carstensen’s group had looked at gender differences and whether these studies have implications for informed consent. To the first question, Dr. Carstensen responded that although she had considered this question, she could not answer based on the studies that have been done. However, it is possible to manipulate experimentally the effects within individuals by shifting time horizons (combined with findings from longitudinal work suggesting similar patterns). She noted also that her group has run experience-sampling studies for the past 10 years and seen some longitudinal replication of initial cross-sectional findings. To Dr. Ganguli’s second question, Dr. Carstensen responded that age-gender interactions had not appeared. To the third question, she responded that the studies had important implications for informed consent but that no studies specifically exploring informed consent had been done.

Dr. Tinetti asked whether Dr. Carstensen had seen more heterogeneity among the older population. Dr. Carstensen responded that no consistent variation had been seen. In response to a question from Dr. Tinetti regarding mechanisms, Dr. Carstensen proposed that the changes were related to motivation. When time horizons are perceived as vast, people are willing to take risks to prepare for a long nebulous future. On the other hand, as people age, they are less willing to do something unpleasant, even if it means a future gain.

C. Neuroscience and Neuropsychology of Aging: TDP-43, A New Class of Proteinopathies in Neurodegenerative Diseases

Dr. Virginia Lee (University of Pennsylvania School of Medicine and a member of Council) presented her work on proteinopathies in the neurodegenerative diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Frontotemporal lobar degeneration (FTLD) refers to a clinically, genetically, and neuropathologically heterogeneous group of neurodegenerative disorders and is the third most common form of dementia after Alzheimer’s disease and dementia with Lewy bodies. The term FTLD reflects the prominent frontal and temporal lobe atrophy seen in these patients by neuropathological examination. A characteristic feature in most FTLD brains is the formation of abnormal protein inclusions in neurons and glial cells. Immunohistochemically, FTLD can be broadly subdivided into disorders with tau-positive inclusions (e.g., Pick’s disease, corticobasal degeneration, and progressive supranuclear palsy) and those with ubiquitin-positive, tau- and α-synuclein negative inclusions, termed FTLD-U, which is the most common neuropathological form underlying FTLD. While tau has been known as the protein building block of the inclusions in tauopathies for many years, and its role in the pathogenesis of neurodegenerative disorders is established, especially after identification of mutations in the microtubule associated protein tau gene (MAPT) in familial tauopathies, the ubiquitinated protein forming the pathologic inclusions in FTLD-U have remained unknown until recently when exhaustive antibody-based and biochemical experiments eventually allowed Dr. Lee’s group to identify the TAR-DNA binding protein 43 (TDP-43) as the disease protein in FTLD-U.

Studies by Dr. Lee and her colleagues have also shown that TDP-43-positive inclusions are present in neurons and oligodendrocytes of gray and white matter of FTLD-U patients with and without motor neuron disease (MND) as well as ALS. TDP-43 also was found to be abnormally modified in FTLD-U, suggesting that TDP-43 is directly involved in the pathogenesis of FTLD-U. In addition to the normal 43 kDa protein, a disease-specific biochemical profile of TDP-43 was evident in detergent-insoluble, urea-soluble protein extracts from FTLD-U brains. Specifically, pathological TDP-43 was found to be hyperphosphorylated, ubiquitinated, and N-terminally truncated, thereby generating abnormal species of TDP-43 migrating with a higher molecular mass at ~45 kDa, as well as a smear of very high molecular mass proteins and C-terminal fragments of ~25 kDa, respectively, in immunoblots of FTLD-U extracts. The presence and extent of this pathologic signature in affected cortical gray and white matter as well as spinal cord roughly corresponds with the density of TDP-43 positive inclusions detected by immunohistochemistry.

TDP-43 is a 414 amino acid protein first cloned as a human protein capable of binding to the transactive response DNA of human immunodeficiency virus type 1 and later identified as part of a complex involved in splicing of the cystic fibrosis transmembrane conductance regulator gene. It is a highly conserved and ubiquitously expressed nuclear protein with two RNA recognition motifs and a glycine-rich C-terminal region, which may function as a transcription repressor and initiator of exon skipping. Finally, TDP-43 may act as scaffold for nuclear bodies through interaction with survival motor neuron proteins. Thus, TDP-43 is predominantly a nuclear protein. However TDP-43 is found in neuronal cytoplasmic inclusions, dystrophic neuritis, and neuronal intranuclear inclusions as well as in oligodendrocytes as glial cytoplasmic inclusions. Notably, while physiological TDP-43 is detectable in the nuclei of unaffected neurons and some glial cells, cells harboring the inclusions show a dramatic loss of normal nuclear TDP-43 staining, raising the possibility that some essential normal function of TDP-43 may be lost in FTLD-U.

Since TDP-43 proteinopathy underlies sporadic and familial forms of FTLD-U and ALS, these diseases may represent a clinicopathological syndrome with mechanisms linked to the abnormal hyperphosphorylation, ubiquitination, and cleavage of pathological TDP-43 to generate C-terminal fragments in affected brain and spinal cord of FTLD-U and ALS. In addition to FTLD-U and ALS, TDP-43 neuropathology has been reported in a subset of cases with Alzheimer’s disease, Lewy body variant of Alzheimer’s disease, Guam ALS/PDC, and Parkinson’s disease dementia particularly in the hippocampus. This TDP-43 neuropathology may represent a new proteinopathy. Indeed, TDP-43 proteinopathies are distinct from most other neurodegenerative disorders wherein protein misfolding leads to brain amyloidosis since pathological TDP-43 forms neuronal and glial inclusions lacking the features of brain amyloid deposits. Finally, the identification of TDP-43 proteinopathies will allow for the development of better diagnostics and therapeutics for FTLD-U and ALS.

In response to questions about the nature of the disease-associated variant, Dr. Lee noted rumors that mutations in TDP-43 have been identified. However, she added that there was no clear evidence to suggest how TDP-43 became ubiquitinated or hyperphosphorylated. She speculated that a scenario similar to that for tau or synuclein would occur and that mutations most likely would be identified. In response to questions from Dr. Khosla, Dr. Lee speculated that accumulated TDP-43 causes cell death or dysfunction rather than serving as a disease marker.

D. What Doesn’t Kill You, Makes You Live Longer: C. elegans Essential Genes in Aging

Dr. Gary Ruvkun (Massachusetts General Hospital and a Council member) discussed comprehensive screens his group has conducted to identify genes involved in regulating life span in C. elegans. He noted earlier studies showing that worms carrying a mutation (daf-2) in the insulin receptor lived longer, and he suggested that the pathway at work under these conditions resembled the pathway involved in longevity associated with caloric restriction in mice. Dr. Ruvkun’s group performed RNA interference screens of 16,000 genes and found 90 that increase life span to about 1.5 times the normal life span. A large number of genes were associated with the insulin pathway, but surprisingly, the insulin receptor was not identified in this screen. Although other poorly understood factors appeared to play a role, the results of these screens suggested that insulin-signaling pathways play an important role in the regulation of life span.

In another screen, where Dr. Ruvkun and his group looked for suppression of increased life span in daf-2 mutants, 197 clones were identified. Of these, 81 were specific to the daf-2 mutation, and 57 were more general. Among these were DAF-16/FOXO, which is a major target for insulin signaling and has been largely studied in diabetes and endocrine research. The majority of the more potent genes identified in this screen were general and represented many pathways, such as those regulating RNA. However, the daf-2-specific genes were highly enriched for endocytosis pathways.

In a third screen, Dr. Ruvkun’s group conducted a screen of 2,700 genes essential for C. elegans development and identified 64 genes that extended life span by 40–50 percent when inactivated postdevelopmentally. Several of these genes appeared to be translational regulators containing RNA-binding motifs.

Dr. Ruvkun noted that most organisms that go through moltings have arrest points at which they assess their environments. He pointed out that life span regulation is a part of normal physiology and that by identifying genes involved in extended life spans, researchers are tapping into the arrest stages organisms use to escape to a better environment. For example, many of the 2,700 proteins his group screened tended to be targets for natural antibiotics. The genes identified might help the animal sense a dangerous environment and stop development until conditions improve. Although nematodes and chordates share a common ancestor, how these results translate to mammalian physiology is not clear.

VII. ADJOURNMENT

The 101st meeting of the National Advisory Council on Aging was adjourned at 1:25 p.m. on May 16, 2007. The next meeting is scheduled for September 25 and 26, 2007.

VIII. CERTIFICATION

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 Robin Barr, D.Phil.
With assistance by Rose Li and Associates, Inc.

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. (Back to text.)
   
   
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. (Back to text.)
   
   
3. These minutes will be approved formally by the Council at the next meeting on September 25–26, 2007, 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

(Terms end December 31) (*WGoP Member)

Chairperson
Richard J. Hodes, M.D.
Director, National Institute on Aging
National Institutes of Health
Bethesda, MD

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

Peggye Dilworth-Anderson, Ph.D. (2010)
Professor, Health Policy & Administration
Associate Director, Aging and Diversity/ Institute on Aging
University of North Carolina, Chapel Hill
Chapel Hill, NC

Carl Eisdorfer, Ph.D., M.D. (2009)
Knight Professor and Director
Center on Aging
University of Miami
Miami, FL

Lawrence M. Friedman, M.D. (2009)
Independent Consultant
11712 Farmland Drive
Rockville, MD

Mary Ganguli, M.D., M.P.H. (2009)
Professor of Psychiatry, Neurology, and Epidemiology
Department of Psychiatry
University of Pittsburgh
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

S. Michal Jazwinski, Ph.D., (2010)
Professor
Department of Medicine
Tulane University Health Sciences Center
New Orleans, LA

Sundeep Khosla, M.D. (2010)
Professor, Endocrine Research Unit
Division of Endocrinology, Metabolism, & Nutrition
Mayo Clinic College of Medicine
Rochester, MN

*Virginia M.-Y. Lee, Ph.D. (2007)
Professor
Dept of Pathology & Laboratory Medicine
Univ of Pennsylvania School of Medicine
Philadelphia, PA

Mills, Terry L., Ph.D. (2008)
Dean, Division of Humanities & Social Sciences
Morehouse College
Atlanta, GA

*John C. Morris, M.D. (2009)
Professor
Washington University School of Medicine
St. Louis, MO

Orien Reid (2010)
Chairman, Alzheimer's Disease International
President, Consumer Connection
Laverock, PA

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.