GENETIC AND MOLECULAR BASIS OF LONGEVITY

RELEASE DATE:  July 10, 2003

RFA:  AG-04-003

National Institute on Aging (NIA)
 (http://www.nia.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.866

LETTER OF INTENT RECEIPT DATE:  September 22, 2003

APPLICATION RECEIPT DATE:  October 22, 2003  

THIS RFA CONTAINS THE FOLLOWING INFORMATION:
o   Purpose of this RFA
o   Research Objectives
o   Mechanism of Support
o   Funds Available
o   Eligible Institutions
o   Individuals Eligible to Become Principal Investigators
o   Special Requirements
o   Where to Send Inquiries
o   Letter of Intent
o   Submitting an Application
o   Peer Review Process
o   Review Criteria
o   Receipt and Review Schedule
o   Award Criteria
o   Required Federal Citations

PURPOSE OF THIS RFA

The National Institute on Aging (NIA) invites applications for new and 
competing renewal applications for research project grants (R01) to 
support basic research on the genetic and molecular basis of longevity.  
The goals of the "Genetic and Molecular Basis of Longevity" Request for 
Applications (RFA) are to identify and functionally characterize genes 
that play a role in determining and modulating longevity and health span 
and determine the molecular mechanism(s) of action of these Longevity 
Assurance Genes (LAGs).  Longevity Assurance Genes are operationally 
defined as genes that: determine, modulate or promote longevity and 
extend health span; maintain cell, tissue and/or organ function; and 
regulate and/or maintain organismal homeostasis.  A multidisciplinary 
approach to the study of the complex traits of aging and longevity, 
including the application of genetic, molecular and biochemical 
approaches and techniques, has significantly accelerated research 
progress toward an in depth understanding of the genes, proteins, and 
biochemical pathways that modulate and play significant functional roles 
in aging and longevity in both invertebrate and mammalian species.  
Candidate LAGs that fit one or more of the above classifications have 
been identified in several invertebrates (Saccharomyces cerevisiae, 
Drosophila melanogaster, Caenorhabditis elegans), mice and humans.  The 
continued development and application of multidisciplinary scientific 
approaches to the elucidation of the genetic and molecular basis of 
aging and longevity is strongly encouraged in applications submitted in 
response to this RFA.

RESEARCH OBJECTIVES

Research advances in several experimental models of aging and longevity 
including yeast, nematodes, fruit flies, mice, rats and humans have 
clearly established that aging and longevity are, in part, under genetic 
control. Furthermore, several biological processes have been implicated 
in the modulation/regulation of longevity in both invertebrates and 
mammals including insulin/IGF-I-like signaling pathways, antioxidant 
defenses, metabolic regulation/energy metabolism, chromatin stability 
and gene silencing.  The multidisciplinary, interactive research 
approach outlined in this RFA is designed to integrate the genetic, 
molecular and biochemical analysis of various animal and human models of 
longevity with state-of-the-art biotechnology in a concerted effort to 
decipher and understand the fundamental mechanisms which contribute to 
longevity and aging. Enhanced knowledge of these crucial biological 
processes will guide and hasten the development of effective prevention 
and intervention strategies to promote human longevity and extend human 
health span. The scientific objectives of this RFA are: 

o   to stimulate multidisciplinary research focused on discovery and 
functional characterization of the fundamental mechanisms that 
determine and/or regulate longevity and health span
o   to encourage the application of research advances in invertebrates 
and short-lived mammals to understanding the fundamental 
mechanism(s) of human aging and longevity
o   to develop and test experimental intervention strategies that 
promote longevity and extend health span 

MECHANISM OF SUPPORT

This RFA will use the NIH R01 award mechanism.  As the principal 
investigator you will be solely responsible for planning, directing, and 
executing the proposed project.  This RFA is a one-time solicitation.  
Future unsolicited, competing-continuation applications based on this 
research project will compete with all investigator-initiated 
applications and will be reviewed according to the customary peer review 
procedures.  The anticipated award date is July 1, 2004.  Applications 
that are not funded in the competition described in this RFA may be 
resubmitted as NEW investigator-initiated applications using the 
standard receipt dates for NEW applications described in the 
instructions to the PHS 398 application.

This RFA uses just-in-time concepts.  It also uses the non-modular 
budgeting format (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).  This program 
does not require cost sharing as defined in the current NIH Grants 
policy statement at 
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.   

FUNDS AVAILABLE

The NIA intends to commit approximately 6 million dollars in FY2004 to 
fund 15 to 20 new and/or competing renewal grants in response to this 
RFA.  An applicant may request a project period of up to five years and 
a budget for direct costs of up to $350,000. direct costs per year.  
Because the nature and scope of the proposed research will vary from 
application to application, it is anticipated that the size of each 
award will also vary.   Although the financial plans of the NIA provide 
support for this program, awards pursuant to this RFA are contingent 
upon the availability of funds and the receipt of a sufficient number of 
meritorious applications.   

ELIGIBLE INSTITUTIONS

You may submit an application if your institution has any of the 
following characteristics:

o   For-profit or non-profit organizations 
o   Public or private institutions, such as universities, colleges, 
hospitals, and laboratories
o   Units of state and local governments
o   Eligible agencies of the Federal government
o   Domestic or foreign

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to 
carry out the proposed research is invited to work with their 
institution to develop an application for support.  Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are always encouraged to apply for NIH programs.

SPECIAL REQUIREMENTS 

Annual Meetings of Investigators:  Investigators receiving grant awards 
pursuant to this RFA will become members of the NIA Longevity Assurance 
Gene (LAG) Interactive Network.  NIA program staff will schedule and 
organize yearly three-day meetings of the LAG Interactive Network to 
facilitate scientific interactions and data sharing among investigators 
and NIA program staff.  Applicants to this RFA must include $2000 per 
year in the proposed travel budget to cover expenses related to 
attendance at the LAG Interactive Network meetings.

Sharing of Unique Resources and Research Tools:  Investigators receiving 
grants pursuant to this RFA must follow NIH guidelines pertaining to the 
sharing of unique resources, research tools and methodology with the 
scientific community.  That is, unique resources, research tools and 
scientific methodology developed wholly, or in part, by NIH funds are to 
be made available to the scientific research community.  Recipients are 
expected to manage interactions with third parties that have the 
potential to restrict Recipients' ability to disseminate research 
resources and tools developed with NIH funds.  To avoid incurring 
obligations to a third party that conflict with Recipients' obligation 
to the NIH, grant recipients are encouraged to share these principles 
with potential co-sponsors of research projects and third party 
providers of materials.  Recipients should take every reasonable step to 
streamline the process of transferring their own research tools freely 
to other academic research institutions and are encouraged to use the 
Simple Letter Agreement of the Uniform Biological Materials Transfer 
Agreement (UBMTA).  The Appendix of the Principles and Guidelines (see 
below) contains an updated freestanding version of the Simple Letter 
Agreement that is strongly encouraged for transfers of unpatented 
research material among recipients.  For assistance in implementation of 
these principles and guidelines, please refer to:  "Sharing Biomedical 
Research Resources:  Principles and Guidelines for the Recipients of NIH 
Research Grants and Contracts" at 
http://www.ott.nih.gov/policy/rt_guide_final.html or 
http://ott.od.nih.gov/NewPages/64FR72090.pdf.   

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into 
three areas:  scientific/research, peer review, and financial/grants 
management issues.

o Direct your questions about scientific/research issues to:  
  
Anna M. McCormick, Ph.D.
Chief, Genetics and Cell Biology Branch
Genetics Program Director
Biology of Aging Program
National Institute on Aging
Gateway Building, Suite 2C231
Bethesda, MD 20892-2292
Telephone:  (301) 496-6402
FAX:  (301) 402-0010
Email:  mccormia@nia.nih.gov

o Direct your questions about peer review issues to:

Mary Nekola, Ph.D.
Chief, Scientific Review Office
National Institute on Aging
Gateway Building, Suite 2C212
Bethesda, MD  20892-2292
Telephone:  (301) 496-9666
FAX:  (301) 402-0066
Email: nekolam@nia.nih.gov

o Direct your questions about financial or grants management matters to:

Linda Whipp
Grants Management Officer
National Institute on Aging
Gateway Building, Suite 2N212
Bethesda, MD  20892-2292
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email:  whippL@nia.nih.gov

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that 
includes the following information:

o   Descriptive title of the proposed research
o   Name, address, and telephone number of the Principal Investigator
o   Names of key personnel
o   Participating institutions
o   Number and title of this RFA

Although a letter of intent is not required, is not binding, and does 
not enter into the review of the subsequent application, the information 
that it contains allows NIA staff to estimate the potential review 
workload and plan the review.  

The letter of intent is to be sent by the date listed at the beginning 
of this document.  The letter of intent should be sent to:

Mary Nekola, Ph.D.
Chief, Scientific Review Office
National Institute on Aging
Gateway Building, Suite 2C212
Bethesda, MD  20892-2292
Telephone:  (301) 496-9666
FAX:  (301) 402-0066
Email: nekolam@nia.nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  The PHS 398 is 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone: (301) 435-0714, Email: GrantsInfo@nih.gov.

USING THE RFA LABEL:  The RFA label available in the PHS 398 (rev. 
5/2001) application form must be affixed to the bottom of the face page 
of the application.  Type the RFA number on the label.  Failure to use 
this label could result in delayed processing of the application such 
that it may not reach the review committee in time for review.  In 
addition, the RFA title and number must be typed on line 2 of the face 
page of the application form and the YES box must be marked.  The RFA 
label is also available at:  
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.

SENDING AN APPLICATION TO THE NIH:  Submit a signed, typewritten 
original of the application, including the Checklist, and three signed, 
photocopies, in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD 20817 (for express/courier service)

At the time of submission, two additional copies of the application must 
be sent to:

Dr. Mary Nekola
Scientific Review Office 
National Institute on Aging
Gateway Building, Suite 2C212
Bethesda, MD  20892-2292
Bethesda, MD 20814 (for express/courier service)

APPLICATION PROCESSING:  Applications must be received on or before the 
application receipt date listed in the heading of the RFA.  If an 
application is received after that date, it will be returned to the 
applicant without review.

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignments within 8 weeks.  

The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA that is essentially the same as one currently 
pending initial review, unless the applicant withdraws the pending 
application.  However, when a previously unfunded application, 
originally submitted as an investigator-initiated application, is to be 
submitted in response to this RFA, it is to be prepared as a NEW 
application.  That is, the application for the RFA must not include an 
Introduction describing the changes and improvements made, and the text 
must not be marked to indicate the changes.  While the investigator may 
still benefit from the previous review, the RFA application is not to 
state specifically how.  

PEER REVIEW PROCESS

Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NIA.  Incomplete and/or non-responsive 
applications will be returned to the applicant without further 
consideration.

Applications that are complete and responsive to this RFA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by the NIA in accordance with the review criteria 
stated below.   As part of the initial scientific merit review, all 
applications will:

o   Receive a written critique
o   Undergo a process in which only those applications deemed to have 
the highest scientific merit, generally the top half of 
applications under review, will be discussed and assigned a 
priority score
o   Receive a second level review by the National Advisory Council on 
Aging (NACA)

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
In the written comments, reviewers will be asked to discuss the 
following aspects of the application in order to judge the likelihood 
that the proposed research will have a substantial impact on the pursuit 
of these goals:

o   Significance
o   Approach
o   Innovation
o   Investigator
o   Environment

The scientific review group will address and consider each of these 
criteria in assigning the overall score of the application, weighting 
them as appropriate for each application.  The application does not need 
to be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.  For example, 
an investigator may propose to carry out important work that by its 
nature is not innovative but is essential to move a field forward.

SIGNIFICANCE:  Does this study address an important problem?  If the 
aims of the application are achieved, how will scientific knowledge be 
advanced?  What will be the effect of these studies on the concepts or 
methods that drive this field?

APPROACH:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of 
the project?  Does the applicant acknowledge potential problem areas and 
consider alternative tactics?

INNOVATION:  Does the project employ novel concepts, approaches or 
methods?  Are the aims original and innovative?  Does the project 
challenge existing paradigms or develop new methodologies or 
technologies?

INVESTIGATOR:  Is the investigator appropriately trained and well suited 
to carry out this work?  Is the work proposed appropriate to the 
experience level of the principal investigator and other researchers 
involved?

ENVIRONMENT:  Does the scientific environment in which the work will be 
done contribute to the probability of success?  Do the proposed 
experiments take advantage of unique features of the scientific 
environment or employ useful collaborative arrangements?  Is there 
evidence of institutional support?

ADDITIONAL REVIEW CRITERIA:  In addition to the above criteria, the 
following items will be considered in the determination of scientific 
merit and the priority score:

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK:  The involvement of 
human subjects and protections from research risk relating to their 
participation in the proposed research will be assessed.  (See criteria 
included in the section of Federal Citations, below).  

INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH:  The adequacy 
of plans to include subjects from both genders, all racial and ethnic 
groups (and subgroups) and children as appropriate for the scientific 
goals of the research.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the sections 
on Federal Citations, below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH:  If vertebrate animals 
are to be used in the project, the five items under Section f of the PHS 
398 Research Grant Application Instructions (rev. 5/2001) will be 
assessed.

ADDITIONAL CONSIDERATIONS

BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.  

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:  September 22, 2003
Application Receipt Date:  October 22, 2003
Peer Review Date:  February-March 2004
Council Review:  May 2004
Earliest Anticipated Start Date:  July 1, 2004

AWARD CRITERIA

Award criteria that will be used to make award decision include:

o   Scientific merit (as determined by peer review)
o   Availability of funds
o   Programmatic priorities

REQUIRED FEDERAL CITATIONS

HUMAN SUBJECTS PROTECTION:  Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated 
with reference to the risks to the subjects, the adequacy of protection 
against these risks, the potential benefits of the research to subjects 
and others, and the importance of the knowledge gained or to be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm 

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH:  It is the 
policy of the NIH that women and members of minority groups and their 
subpopulations must be included in all NIH-supported clinical research 
projects unless a clear and compelling justification is provided 
indicating that inclusion is inappropriate with respect for the health 
of the subjects or the purpose of the research.  This policy results 
from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-
43).

All investigators proposing clinical research should read the "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research – Amended, October, 2001"published in the NIH Guide for Grants 
and Contracts on October 9, 2001 
(http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm).
The amended policy incorporates: the use of an NIH definition 
of clinical research; updated racial and ethnic categories in compliance 
with OMB standards; clarification of language governing NIH-defined 
Phase III clinical trials consistent with the new PHS Form 398; and 
updated roles and responsibilities of NIH staff and the extramural 
community.  The policy continues to require for all NIH-defined Phase 
III clinical trials that:  a) all applications or proposals and/or 
protocols must provide a description of plans to conduct analyses, as 
appropriate, to address differences by sex/gender and/or racial/ethnic 
groups, including subgroups if applicable; and b) investigators must 
report annual accrual and progress in conducting analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:  NIH 
policy requires education on the protection of human subject 
participants for all investigators submitting NIH proposals for research 
involving human subjects.  You will find this policy announcement in the 
NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. 

HUMAN EMBRYONIC STEM CELLS (hESC):  Criteria for federal funding of 
research on hESCs can be found at 
http://stemcells.nih.gov/index.asp and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  
Only research using hESC lines that are registered in the NIH Human 
Embryonic Stem Cell Registry will be eligible for Federal funding (see 
http://escr.nih.gov).  It is the responsibility of the applicant to 
provide the official NIH identifier(s) for the hESC line(s) to be used 
in the proposed research.  Applications that do not contain this 
information will be returned without review.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:  
The Office of Management and Budget (OMB) Circular A-110 has been 
revised to provide public access to research data through the Freedom of 
Information Act (FOIA) under some circumstances.  Data that are (1) 
first produced in a project that is supported in whole or in part with 
Federal funds and (2) cited publically and officially by a Federal 
agency in support of an action that has the force and effect of law 
(i.e., a regulation) may be accessed through FOIA.  It is important for 
applicants to basic scope of this amendment.  NIH has provided guidance 
at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.  

Applicants may wish to place data collected under this RFA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application 
should include a description of the archiving plan in the study design 
and include information about this in the budget justification section 
of the application.  In addition, applicants should think about how to 
structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under 
this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  
The Department of Health and Human Services (DHHS) issued final 
modification to the "Standards for Privacy of Individually Identifiable 
Health Information", the "Privacy Rule," on August 14, 2002.  The 
Privacy Rule is a federal regulation under the Health Insurance 
Portability and Accountability Act (HIPAA) of 1996 that governs the 
protection of individually identifiable health information, and is 
administered and enforced by the DHHS Office for Civil Rights (OCR). 
Those who must comply with the Privacy Rule (classified under the Rule 
as "covered entities") must do so by April 14, 2003  (with the exception 
of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule 
reside with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, 
including a complete Regulation Text and a set of decision tools on "Am 
I a covered entity?"  Information on the impact of the HIPAA Privacy 
Rule on NIH processes involving the review, funding, and progress 
monitoring of grants, cooperative agreements, and research contracts can 
be found at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs IN NIH GRANT APPLIATIONS OR APPENDICES:  All applications and 
proposals for NIH funding must be self-contained within specified page 
limitations.  Unless otherwise specified in an NIH solicitation, 
Internet addresses (URLs) should not be used to provide information 
necessary for the scientific review because reviewers are under no 
obligation to view the Internet sites.  Furthermore, we caution 
reviewers that their anonymity may be compromised when they directly 
access an Internet site.

HEALTHY PEOPLE 2010:  The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of 
"Health People 2010", a PHS-led national activity for setting priority 
areas.  Potential applicants may obtain a copy of "Healthy People 2010" 
at http://www.health.gov/healthypeople. 

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject 
to the intergovernmental review requirements of Executive Order 12372 or 
Health System Agency Review.  Awards are made under the authorization of 
Sections 301 and 405 of the Public Health Service Act as amended (42 USC 
241 and 284) (93.866) and under Federal Regulations 42 CFR 52 and 45 CFR 
Parts 74 and 92.

All awards are subject to the terms and conditions, cost principles, and 
other considerations described in the NIH Grants Policy Statement.  The 
NIH Grants Policy Statement can be found at 
http://grants.nih.gov/grants/policy/policy.htm. 

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, 
Public Law 103-257, the Pro-Children Act of 1994, prohibits smoking in 
certain facilities (or in some cases, any portion of a facility) in 
which regular or routine education, library, day care, health care, or 
early childhood development services are provided to children.  This is 
consistent with the PHS mission to protect and advance the physical and 
mental health of the American people.


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