Full Text PA-96-038
NIH GUIDE, Volume 25, Number 11, April 5, 1996
PA NUMBER:  PA-96-038
P.T. 34

  Muscle Disorders 
  Musculoskeletal System 

National Institute on Aging
National Institute of Arthritis and Musculoskeletal and Skin Diseases
The National Institute on Aging (NIA) and the National Institute of
Arthritis and Musculoskeletal Skin Diseases (NIAMS) invite research
applications to elucidate the metabolic/physiological and functional
consequences of sarcopenia in old age.  Sarcopenia is defined as the
loss of skeletal muscle mass, quality and strength.
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas. This PA, The
Significance of Sarcopenia in Old Age is related to the priority area
of chronic diseases and disabling conditions. Potential applicants
may obtain a copy of "Healthy People 2000" (Full Report:  Stock
No.017-001-00474-0 or Summary Report:  Stock No. 017-001-00473-1)
through the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325 (telephone 202-512-1800).
Applications may be submitted by foreign and domestic, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.
Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as Principal Investigators.
Foreign institutions are not eligible for First Independent Research
Support and Transition (FIRST) (R29) awards.
Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the GCRC as a resource for conducting
the proposed research.  If so, a letter of agreement from either the
GCRC Program Director or Principal Investigator should be included
with the application.
This program will use the NIH investigator-initiated research project
grant (R01) and FIRST (R29) award mechanisms.  The total project
period for an application submitted in response to this program may
not exceed five years.  Because the nature and scope of the research
proposed in response to this program may vary, it is anticipated that
the size of awards will vary as well.
The Greek word "sarco" refers to flesh and "penia" indicates a
deficiency.  "Sarcopenia" is a generic term for the loss of skeletal
muscle mass, quality, and strength that can lead to frailty in the
elderly.  Examples of skeletal muscle properties that contribute to
its overall quality include, but are not limited to:  contractility,
fiber size and type, fatiguability, hormone responsiveness, glucose
uptake/metabolism and capillary density.  Sarcopenia is believed to
be due predominantly to disuse atrophy of skeletal muscle fibers.
However, age-associated changes in myofibrillar protein metabolism,
nutritional status, neuromuscular function and in the production of,
or tissue responsiveness to trophic factors, may also represent
important underlying causes of sarcopenia.  Currently the
pathophysiology and the sequelae of sarcopenia are poorly understood
and thus interventions to either prevent, retard or reverse this
condition are extremely limited.  To address these issues, the NIA
convened a multidisciplinary group of clinical and basic
investigators at the "Workshop on Sarcopenia" (held September 19-21,
1994) to (1) review the current knowledge base on the epidemiology,
pathophysiology, public health impact and potential therapeutic
approaches for sarcopenia and (2) identify promising avenues of
future research in each of these areas.  The proceedings and summary
of the research recommendations from this workshop are published in
the special issue "Workshop on Sarcopenia:  Muscle Atrophy in Old
Age" of the Journals of Gerontology (Vol. 50A) 1995.  This PA seeks
to promote the research priorities identified at the workshop that
relate to advancing our understanding of the clinical manifestations
of sarcopenia in the aging population.
Even though a variety of studies have noted correlations between age-
related changes in parameters of skeletal muscle quality (e.g., mass,
fiber type composition, strength), with metabolic/physiological and
functional impairments, a full appreciation of the consequences of
sarcopenia and of the magnitude of the potential public health
problem it poses remains to be ascertained.  With respect to
functional impairments, it is generally recognized that muscle
weakness in the upper and lower extremities can contribute to gait
problems, falls and ultimately to the loss of physical functional
independence.  Yet, very little is known about which age-related
changes in specific muscle properties (e.g., mass, strength, torque
development, fiber type distribution, fatigue characteristics,
contractile properties) significantly affect physical function and
performance of specific tasks (e.g., walking, maintaining balance,
Furthermore, the metabolic/physiological consequences of sarcopenia
in the elderly remain to be systematically investigated.  Assumptions
have been made that age-related changes in muscle mass are associated
with a reduced metabolic rate (leading to obesity and increased risk
for chronic diseases) and in the development of non-insulin dependent
diabetes mellitus in old age.  The extent to which such metabolic
changes can be attributed solely to age-related loss of muscle mass
or to complex changes in body composition (e.g., increases in body
fat) remains to be established.  Controversy also exists over other
putative morbid consequences of sarcopenia, which include
osteoporosis (e.g., potential relationship between muscle weakness
and decreased bone quality), increased susceptibility to fracture
(independent of risk of falling), and altered thermoregulation (e.g.,
decreased thermogenic capacity of muscle due to reduced mass).
Clarification through quantitative assessments of the
interrelationship(s) between muscle mass/quality and the potential
metabolic/physiological and functional consequences are essential
steps towards the development of new approaches for clinical
diagnosis, new insights into the underlying mechanisms and ultimately
to the development of effective interventions for sarcopenia.
The aims of this PA are to:  (1) determine the clinical significance
of sarcopenia in the elderly, by identifying the age-related changes
in muscle quality that have morbid and functional implications and
(2) establish quantitative relationships ("dose-effect" or threshold
levels) between alterations in muscle quality and
metabolic/physiologic impairment or functional abilities.  Studies
that will compare elderly populations with varying degrees of
frailty, encompass a wide age range, including the "oldest old" and
utilize multidisciplinary approaches to address these aims are
especially encouraged.  Topics of interest include, but are not
limited to:
o  Epidemiologic approaches on the relationship between decreases in
muscle mass/quality and decreases in functional abilities.
o  Characterization of potential gender and ethnic differences in the
morbid and functional consequences of sarcopenia.
o  Studies that combine measures of age-related changes in muscle
properties (e.g., mass, fiber type, capillary density) and muscle
performance (e.g., force, power, torque, fatigue characteristics)
within the same individuals, and then correlate such changes with
metabolic and functional impairments.
o  Systematic evaluation of the key muscle groups involved in
activities of daily living and the nature of the contribution(s) of
the key muscle groups to successful task performance.
o  Characterization of age-related changes in skeletal muscle
properties (e.g., strength, power, force, torque, range of motion,
rate of force or torque development) responsible for deficits in
functional status.
o  Establishing "dose-response" relationships between age-related
changes in muscle properties (including biomechanical parameters) and
gait, balance and functional status.
o  Determination of the relative contributions of age-associated
changes in intrinsic contractile properties of muscle, the central
and peripheral nervous systems to impairments in physical
o  Characterization of metabolic/physiological changes due to
decreased muscle mass or quality.
o  Role of age-related changes in fat free mass and skeletal muscle
metabolism in the development of obesity and insulin resistance in
the elderly.
o  Clarification of the effects of sarcopenia on bone density, risk
for fractures and attenuation of impact forces of falls.
It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to 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) and supersedes and strengthens the previous policies.
All investigators proposing research involving human subjects should
read the "NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.
Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.
Applications are to be submitted on the grant application form PHS
398 (rev. 5/95) and will be accepted at the standard application
deadlines as indicated in the application kit.  Applications kits are
available at most institutional offices of sponsored research and may
be obtained from the Grants Information Office, Office of Extramural
Outreach and Information Resources, National Institutes of Health,
6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone
301/710-0267, email:  ASKNIH@odrockm1.od.nih.gov.  The title and
number of this program announcement must be typed in Section 2 on the
face page of the application.
Applications for the FIRST (R29) award must include at least three
sealed letters of reference attached to the face page of the original
application.  FIRST (R29) award applications submitted without the
required number of reference letters will be considered incomplete
and will be returned without review.
The completed original application and five legible copies must be
sent or delivered to:
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817-7710 (for express/courier service)
Applications will be assigned on the basis of established PHS
referral guidelines.  Applications that are complete will be
evaluated for scientific and technical merit by study sections of the
Division of Research Grants, NIH, in accordance with the standard NIH
peer review procedures. Following scientific-technical review, the
applications will receive a second-level review by the appropriate
national advisory council.
Review Criteria
o  Scientific, technical, or medical significance and originality of
the 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 the resources necessary to perform the research;
o  Appropriateness of the proposed budget and duration in relation to
the proposed research;
o  Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
The initial review group will also examine the provisions for the
protection of human and animal subjects, and the safety of the
research environment.
Scored applications will compete for available funds with all other
scored applications assigned to that Institute/Center.  The following
will be considered in making funding decisions:
o  Quality of the proposed project as determined by peer review; o
Availability of funds; and
o  Program balance among research areas of the program announcement.
Written and telephone inquiries are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
Chhanda Dutta, Ph.D.
Geriatrics Program
National Institute on Aging
Gateway Building, Suite 3E327
7201 Wisconsin Avenue, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-6761
FAX:  (301) 402-1784
Email:  DuttaC@gw.nia.nih.gov
Richard W. Lymn, Ph.D.
Muscle Biology Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building, Room 5AS49E, MSC 6500
Bethesda, MD  20892-6500
Telephone: (301) 594-5128
FAX:  (301) 480-4543
Direct inquires regarding fiscal matters to:
Mr. Joseph Ellis
Grants and Contracts Management Office
National Institute on Aging
Gateway Building, Suite 2N212
7201 Wisconsin Avenue, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email:  EllisJ@gw.nia.nih.gov
Joseph L. Brown
Grants Management Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building, Room 5AS-43J, MSC 6500
Bethesda, MD  20892-6500
Telephone:  (301) 594-3507
FAX:  (301) 480-4543
Email:  brownj@ep.niams.nih.gov
This program is described in the Catalog of Federal Domestic
Assistance Nos. 93.866 and 93.846.  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 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.
The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  In addition, Public Law 103-227, 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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