Subject: NIH GUIDE - RFA AG-91-17 - V20(43) 11/15/91
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Fri, 15 Nov 91 09:09 EST

Hi Paul,
    This looks like the last NIH item today. Please post to the
NIH Listserver as:
        RFAAG-91-17.911115
                          Thanks.  Have a nice weekend.
                                                       Dottie
 ---------------------------- Text of forwarded message -----------------------
 
$$XID RFA AG9117 AG-91-17 P1O1 *****************************************
 
DEVELOPMENT OF BIOMARKERS OF AGING
 
RFA:  AG-91-17
 
P.T. 34; K.W. 0710010, 0760003
 
National Institute on Aging
 
Letter of Intent Receipt Date:  December 16, 1991
Application Receipt Date:  February 19, 1992
 
PURPOSE
 
One of the mandates of the National Institute on Aging (NIA) is to
develop research approaches to extend the vigorous and productive years
of life.  In response to this mandate, the NIA has begun a process with
the long-term objective of assessing interventions that affect aging.
In order to test the effects of interventions, particularly
interventions on humans, a testing strategy that is both scientifically
valid and achievable in significantly less than a human lifespan is
essential.  This need for a workable test strategy has fostered
interest in the development of biomarkers of aging.  The concept of
biomarkers of aging rests on the assumption that the passage of time is
only indirectly related to age.  If, in a biological sense, the
lifespan of a humman and the lifespan of a mouse are equivalent, then
the passage of time is a very poor measure of age. Biomarkers of aging
would be measures that accurately reflect rate of aging and, therefore,
predict longevity, yet could be obtained in a small portion of the
lifespan.
 
The major goal of the research to be supported is to continue the
development of a panel of biomarkers of aging constituted from the
biomarkers developed in response to this and a previously announced
Request For Application (see Development of Biomarkers of Aging, NIH
GUIDE, Vol. 16, No. 19, June 5, 1987).  To achieve this goal, two
separate types of applications are solicited in this RFA:  one type
addresses the assessment of potential biomarkers of aging, and the
other type addresses the statistical analyses of these potential
biomarkers to provide a panel of statistically valid biomarkers useful
for testing future interventions in the aging process.  Completion of
the objectives of the biomarker research program is expected to take
five additional years and should result either in the development of a
definitive panel of biomarkers for use in intervention testing or in
positive evidence that the biomarkers strategy is not workable in these
species.
 
ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by domestic and foreign, for-profit or
nonprofit, private, and public organizations,  such as universities,
colleges, hospitals, laboratories, units of State or local governments,
and eligible agencies of the Federal Government.  Applications from
minority individuals and women are encouraged.
 
For the purposes of continuity and to receive the full benefit of 10
years of focus and support in biomarkers of aging research,
applications will be accepted from investigators in either of the
following two categories related to experience with biomarkers of aging
research:
 
o  investigators currently conducting NIA-funded Biomarkers of Aging
Research projects, or
 
o  investigators who can demonstrate an active research focus for the
previous four or more years on biomarkers of aging, regardless of the
source of research support, using the same rodent genotypes available
from the NIA/National Center for Toxicological Research biomarker
rodent colony described below, are able and willing to use animals from
the NIA/NCTR biomarker colony, and have suitable facilities for housing
these animals.
 
There are no similar experience restrictions on the investigators
applying for the Statistical Analyses of Biomarkers of Aging research.
 
MECHANISM OF SUPPORT
 
This RFA will use the National Institutes of Health (NIH) research
project (RO1) grants.  Responsibility for the planning, direction, and
execution of the proposed project will be solely that of the applicant.
Awards will be administered under PHS grants policy as stated in the
Public Health Service Grants Policy Statement, DHHS Publication No.
(OASH) 82-50,000, revised October 1, 1990.
 
FUNDS AVAILABLE
 
A total of $2,000,000 is expected to be available for this program in
FY 1993.  Funds for subsequent years are expected to range from
$1,500,000 to $2,000,000 per year.  It is anticipated that individual
awards will range from $75,000 to $150,000 per year in direct costs.
Collaborative applications or applications to test more than one type
of potential biomarker could request more than $150,000 per year in
direct costs with sufficient justification.  A maximum of 14 awards for
the Biomarker of Aging Research and one award for the Statistical
Analysis of the Biomarkers of Aging Research are anticipated.
 
The award of grants pursuant to this RFA is contingent upon receipt of
appropriated funds for this purpose.  This RFA is a one-time
invitation.  There are no plans for future reissuance.  The duration of
proposed projects may be up to five years.  The start date for funded
projects will be approximately April 1, 1993.
 
RESEARCH OBJECTIVES
 
This RFA is to encourage the continued development of research projects
that utilize the available colony of rodents to conduct biomarker
research.  Two types of applications will be considered:
 
A.  Applications for Biomarkers of Aging Research
 
The objective of applications submitted in response to this request
should be the continued development and testing of one or more
biomarkers of aging using mice and/or rats obtained from the NIA/NCTR
biomarker research colony.  In order to allow for the development of a
broadly based panel of biomarkers, applications are solicited from a
wide variety of possible approaches.  Applications will be accepted for
biomarker development for any one or more of the following types:
 
1.  Immunologic
2.  Sensory and motor function
3.  Learning and memory
4.  Neuroendocrine
5.  Cardio-pulmonary
6.  Endocrine-metabolic
7.  Renal function
8.  Reproductive function
9.  Chromosomal
10.  Neuromuscular
11.  Connective tissue
12.  Clinical chemistry
13.  Molecular and cellular alterations
14.  Other promising biomarkers not included above.
 
By the final year of the proposed project, the investigator will be
expected to obtain data for the proposed biomarker using non-invasive
methods, and the proposed biomarker must be applicable to the human
population.
 
The research plan for biomarker development must include evaluation of
each potential biomarker for reproducibility, sensitivity, significance
of rate of change over the lifespan, temporal pattern of changes,
non-lethality, degree of invasiveness required, potential functional
importance to human aging, simplicity, and cost-effectiveness.
 
As one step in a plan to implement testing of potential biomarkers, the
NIA, in collaboration with the NCTR, has available a colony of four
mouse genotypes and three rat genotypes as a resource for rodent
biomarker research.  Mice available in this colony include C57BL/6NNIA,
DBA2/NNIA, B6D2F1 (C56BL/6NNIA X DBA2/NNIA), B6C3F1 (C57BL/6 X C3H)
ranging in age from three to 30 months (approximately 22,000/year).
Available rats include Fischer 344, Brown-Norway, and F344 X BN hybrids
ranging in age from three to 24 months (approximately 6,000/year).
Both male and female rodents are available.  This major animal resource
has provided a suitable test population for 14 investigator-initiated
biomarker research projects over the previous four years.  In order to
allow testing of biomarker sensitivity to interventions that alter
lifespan, and since dietary restriction is the only currently available
intervention that reliably alters lifespan in rodents, ad libitum fed
and dietary restricted animals of each genotype will be available.
Diets used in the NIA/NCTR colony will be made available for shipment
to investigators to assure diet continuity for all animals.  Applicants
must include funds for diet acquisition and shipment.  All NIA/NCTR
animals are maintained in Specific Pathogen Free (SPF) barrier
facilities.  Applicants must demonstrate the ability to house animals
received from this colony in similar or equivalent barrier conditions.
This can be achieved either with existing barrier facilities that can
be devoted to this activity, or by the use of laminar flow caging in
non-barrier rooms devoted solely to this project.  In cases where it is
necessary to propose the use of laminar flow caging, applications may
include requests for funds for laminar flow cages and associated
equipment.  Requests for alteration and renovation of animal facilities
or rooms will not be accepted.
 
Collaborative research applications from investigators will be accepted
where biomarker development requires multiple research skills not
available in a single institution, where collaboration enhances the
value of the research conducted at the cooperating institutions, or
where multiple use of animals is scientifically feasible and allows
significant research cost economies.
 
The applicant is permitted to propose studies leading to the
elucidation of the physiologic or molecular mechanism(s) by which the
biomarker studied constitutes a biomarker of aging, or the mechanism(s)
by which caloric restriction produces lifespan extension in these
animals.
 
Applications must clearly state the type, number, and use schedule of
all animals needed for the proposed research.  Where multiple or shared
uses of animals are proposed, each relevant application must clearly
show which animals are shared and which are not.  Animals from the
NIA/NCTR biomarker colony will be shipped to investigators by preferred
air freight.
 
Only costs for investigator-reared animals, if required by the proposed
research design, should be included.  Applications that include the use
of investigator-reared animals must show a clear rationale for using
such animals in addition to NIA/NCTR colony animals.  Applications that
do not propose biomarker of aging research or that do not include the
use of NIA/NCTR colony animals will not be accepted.
 
B.  Applications for the Statistical Analysis of Biomarkers of Aging
Research
 
The goal of the applications proposed for this segment of the RFA is to
bring together the results of all of the research conducted as a result
of this Biomarkers of Aging Research RFA, using the procedures of
mathematical statistics, to permit a statistically valid assessment of
the gerontologic age of rodents of the genotype specified herein using
a panel of applicable biomarkers of aging.  Applicants may obtain a
description of ongoing research supported by the NIA Biomarkers of
Aging program from the program administrator listed under INQUIRIES of
this RFA.  It is anticipated that a single successful applicant will be
able to accomplish this task, consequently a single award will be made.
 
SPECIAL REQUIREMENTS
 
In order to facilitate the achievement of this goal, the Principal
Investigators of successful applications will be expected to meet
annually to exchange information and to address progress and problems.
Applications in response to this request should include funds for one
trip each year lasting approximately three days to attend this meeting
in addition to any other travel requirements.
 
REVIEW CONSIDERATIONS
 
Applications will be reviewed by the NIA staff for responsiveness to
the goals of the RFA.  Applications judged by the NIA to be non-
responsive will be returned to the applicant without review.
Applications responsive to this RFA will be evaluated for scientific
and technical merit by an initial review group within  NIA that will be
convened solely to review these applications.   Applications may first
receive a preliminary review by a subcommittee of the review panel to
establish those applications deemed to be competitive.  Those
applications judged to be non-competitive will be so designated, and an
abbreviated summary statement noting the major areas of concern will be
sent to the Principal Investigator.  Applications judged to be
competitive will be given full review.  Following review by the initial
review group, the applications will be considered by the National
Advisory Council on Aging.
 
The factors to be considered in the evaluation of the scientific merit
of each application will be the responsiveness to the intent of this
RFA, and those factors used in the review of traditional
research-project grant applications and the past record of performance
in biomarkers of aging research.  Awards will be made on the basis of
scientific merit and the need to fund applications that provide a broad
spectrum of potential biomarkers.
 
Review criteria for RFAs are generally the same as those for
unsolicited research grant applications.
 
o  scientific, technical, or medical significance and originality of
proposed research;
 
o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;
 
o  qualifications and research experience of the Principal Investigator
and staff, particularly but not exclusively in the area of the proposed
research;
 
o  availability of resources necessary to perform the research;
 
o  appropriateness of the proposed budget and duration in relation to
the proposed research; and
 
o  if an application involves activities that could have an adverse
effect upon humans, animals, or the environment, the adequacy of the
proposed means for protecting against or minimizing such effects.
 
APPLICATION PROCEDURES
 
The research grant application form PHS 398 (rev. 10/88, reprinted
9/89) must be used in applying for these grants.  These forms are
available at most institutional business offices; from the Office of
Grants Inquiries, Division of Research Grants, National Institutes of
Health, 5333 Westbard Avenue, Room 449, Bethesda, MD  20892, telephone
(301) 496-9797; and from the NIH program administrator named below.
 
The RFA label available in the 10/88-9/89 revision of PHS 398
application form must be affixed to the bottom of the face page.
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, "Development of Biomarkers of
Aging" and the RFA number must be typed on line 2 of the face page of
the application form and check the YES box.
 
Submit a signed typewritten original of the application, including the
Checklist, and four signed, exact photocopies, in one package to:
 
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892
 
At time of submission, two additional copies of the application must
also be sent to:
 
Chief
SRO/OEA
National Institute on Aging
7201 Wisconsin Avenue
Bethesda, MD  20892
 
Applications must be received by February 19, 1992.  If an application
is received after that date, or if it is incomplete, it will be
returned to the applicant.  Additional or revised material will not be
accepted after the receipt date.  Also, the Division of Research Grants
(DRG) will not accept any application in response to this announcement
that is essentially the same as one currently pending initial review,
unless the applicant withdraws the pending application.  Nor will the
DRG accept any application that is essentially the same as one already
reviewed.  This does not preclude the submission of substantial
revisions of applications already reviewed, but such applications must
include an introduction addressing the previous critique.
 
LETTER OF INTENT
 
Prospective applicants are encouraged to submit to the program
administrator indicated below a letter of intent to apply, post-marked
no later than December 16, 1991, that includes a descriptive title of
the proposed research, the name, address and telephone number of the
Principal Investigator, the identities of other key personnel and
participating institutions, and the number and title of this RFA.  The
letter of intent is not mandatory and does not influence the review or
funding decisions, but it will enable the NIA to plan the review.
INQUIRIES
 
Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.
 
Direct inquiries regarding programmatic issues to:
 
Richard L. Sprott, Ph.D.
Associate Director, BAP
National Institute on Aging
7201 Wisconsin Avenue
Bethesda, MD  20892
Telephone:  (301) 496-4996
 
Direct inquiries regarding fiscal matters to:
 
Ms. Mary Burton
Grants Management Specialist, GCMO
National Institute on Aging
7201 Wisconsin Avenue
Bethesda, MD  20892
Telephone:  (301) 496-1472
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic
Assistance, No. 93.866, Aging Research.  Awards are made under
authorization of the Public Health Service Act, Title IV, Part A
(Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and
285) and administered under PHS grants policies and Federal Regulations
42 CFR Part 52 and 45 CFR Part 74.  This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency Review.