NIH GUIDE, Volume 21, Number 40, November 6, 1992

PA NUMBER:  PA-93-015

P.T. 34



  Endocrine System 

  Immune System 


National Institute On Aging


The National Institute on Aging (NIA) has responsibility for extramural

programs of research and training in immunology and endocrinology

related to aging.  This support has resulted in a better understanding

of the behavior of, and specific changes in, various components of the

immune and endocrine systems in aging.

It is well recognized that changes in the immune and endocrine systems

during aging have profound influences on homeostatic mechanisms of the

body.  Some of these changes may be a result of "normal aging;" others

may be due to environmental factors, such as stress and disease.

Steroid, peptide, and eicosenoid hormones secreted from endocrine

tissues are known to influence the immune system.  Conversely, some

cytokines, interferons and interleukins, modulators of immune system

function, have profound regulatory effects on the endocrine system.

Since both the immune and some components of the endocrine systems

decline with advancing age, it is of interest to explore and delineate

regulatory interactions between the immune and endocrine systems in the

aging mammal.

The purpose of this program announcement is to focus on the

physiological role of the adrenal steroidal androgen precursor,

dehydroepiandrosterone (DHEA), in aging.  DHEA, and its sulfated form,

DHEAS, decrease steadily with age in both animals and humans.  This

decline may represent a biomarker of biological aging.  DHEA/DHEAS

levels have also been found to be depressed in a number of disease

states (eg., systemic lupus erythematosis (SLE), AIDS, cancer,

diabetes, cardiovascular disease) and during stress and trauma (e.g.,

burns, surgery).  Administration of DHEA has been shown to inhibit the

development of obesity and to protect against carcinogenesis in mice.

Recent research has demonstrated that the administration of physiologic

doses of DHEA/DHEAS to aged mice may reverse the age-related

immunological anergy by permitting the production of antibody and

cellular responses at levels comparable to those of fully

immunocompetent mature adult mice.  The pattern of the lymphokine

production was also restored to that of normal mature mice.  DHEAS

administration also has been shown to counteract the inflammatory

production of Interleukin-6 and the effects of corticosteroids

following stress and trauma.


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.

Applications from minority individuals and women are encouraged.

Applicants for K- and F-series awards must be U.S. citizens, non-

citizen nationals, or have been lawfully admitted for permanent

residence at the time of award.


o  Research grant (R01)

o  Program Project grant (P01)

o  First Independent Research Support and Transition (FIRST) award


o  Career grants, which include:  Research Career Development Award

(K04); Clinical Investigator Award (K08); Physician Scientist Award

(individual K11)

o  Fellowships (F32, F33)

Deadlines for applications are as follows:

F-series grants:                     Jan 10, May 10, Sep 10

New R, K, and P-series:              Feb 1, Jun 1, Oct 1

Competing continuation and revised:  Mar 1, Jul 1, Nov 1

Foreign institutions are not eligible to apply for Program Project

(P01) awards, or FIRST awards (R29).


The NIA invites researchers to submit applications for research grants,

career development awards, and postdoctoral fellowships for studies on

the role of DHEA/DHEAS and their metabolic products as they interface

with fundamental aging.  Of particular interest is the pathway of

action and its possible role as a biomarker of aging, including the

decline of the immune system and the propensity for increased disease

in aging.  Of interest also are potential intervention methods to delay

and control the aging process with respect to the susceptibility to

diseases of the immune, endocrine, and other physiologic systems.

Although the interaction of DHEA/DHEAS and their metabolic products and

analogs with components of the immune system and various

pathophysiologic processes is of primary interest in this Program

Announcement, other relevant areas of investigation exploring the

communication between the immune and endocrine systems in aging mammals

are also of interest and are included within the scope of this Program






NIH policy is that applicants for NIH clinical research grants and

cooperative agreements are required to include minorities and women in

study populations so that research findings can be of benefit to all

persons at risk of the disease, disorder or condition under study;

special emphasis must be placed on the need for inclusion of minorities

and women in studies of diseases, disorders and conditions which

disproportionately affect them.  This policy is intended to apply to

males and females of all ages. If women or minorities are excluded or

inadequately represented in clinical research, particularly in proposed

population-based studies, a clear compelling rationale must be


The composition of the proposed study population must be described in

terms of gender and racial/ethnic group.  In addition, gender and

racial/ethnic issues should be addressed in developing a research

design and sample size appropriate for the scientific objectives of the

study. This information must be included in the form PHS 398 in

Sections 1-4 of the Research Plan AND summarized in Section 3,

Recruitment of Individuals from Underrepresented Racial/Ethnic Groups,

and Section 5, Human Subjects.  Applicants are urged to assess

carefully the feasibility of including the broadest possible

representation of minority groups. However, NIH recognizes that it may

not be feasible or appropriate in ALL research projects to include

representation of the full array of United States racial/ethnic

minority populations (i.e., Native Americans  including American

Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks,

Hispanics). The rationale for studies on single minority population

groups must be provided.

For the purpose of this policy, clinical research is defined as human

biomedical and behavioral studies of etiology, epidemiology, prevention

and preventive strategies), diagnosis, or treatment of diseases,

disorders or conditions, including but not limited to clinical trials.

The usual NIH policies concerning research on human subjects also

apply. Basic research or clinical studies in which human tissues cannot

be identified or linked to individuals are excluded. However, every

effort should be made to include human tissues from women and

racial/ethnic minorities when it is important to apply the results of

the study broadly, and this should be addressed by applicants.

For foreign awards, the policy on inclusion of women applies fully;

since the definition of minority differs in other countries, the

applicant must discuss the relevance of research involving foreign

population groups to the United States' populations, including


If the required information is not contained within the application,

the review will be deferred until the information is provided.

Peer reviewers will address specifically whether the research plan in

the application conforms to these policies. If the representation of

women or minorities in a study design is inadequate to answer the

scientific question(s) addressed AND the justification for the selected

study population is inadequate, it will be considered a scientific

weakness or deficiency in the study design and will be reflected in

assigning the priority score to the application.

All applications for clinical research submitted to NIH are required to

address these policies. NIH funding components will not award grants or

cooperative agreements that do not comply with these policies.


Applications are to be submitted on the grant application form PHS 398

(rev. 9/91) and will be accepted at the standard application deadlines

as indicated in the application kit.  The receipt dates for

applications for AIDS-related research are found in the PHS 398

instructions.  National Research Service Award (NRSA) (F32, F33)

applications are to be submitted on grant application Form PHS 416

(rev. 10/91).

Application kits are available at most institutional offices of

sponsored research and may be obtained from the Office of Grants

Inquiries, Division of Research Grants, National Institutes of Health,

Westwood Building, Room  449, Bethesda, MD 20892, telephone

301/496-7441.  The title and number of this announcement must be typed

in Section 2a on the face page of the application.

Applications 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.  In such a case, a letter of agreement from either the GCRC

program director or Principal Investigator could be included with the


The completed original application and five legible copies must be sent

or delivered to:

Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**


All applications in response to this Program Announcement will be

assigned to Initial Review Groups on the basis of the PHS Referral

Guidelines and reviewed by the usual Public Health Service Peer Review

(Study Section) procedures.  They will also be given appropriate

primary and secondary Institute assignments in accordance with

established PHS Referral Guidelines.  The review criteria are the

traditional criteria appropriate to each mechanism.  In accordance with

the standard NIH peer review procedures, research project grant (R01

and R29) applications, fellowships (F32, F33) and research career

development awards (K04) will be reviewed for scientific and technical

merit by appropriate study sections in the Division of Research Grants.

All other applications will be reviewed by review groups of the

appropriate Institute.  Following the Study Section review, the

applications will receive a second-level review by appropriate advisory

councils.  Funding decisions will be based on the above evaluations and

on the availability of funds.


Applications compete for available funds on the basis of scientific

merit with other applications.  The following will be considered in

making funding decisions:

o  Quality of the proposed project as determined by peer review

o  Availability of funds

o  Program balance among research areas of the announcement


Researchers considering an application in response to this announcement

are strongly encouraged to discuss the projects and the range of grant

mechanisms available, with NIA staff.  This can be done either through

a telephone conversation or a brief letter. Applications related to the

health of women and minorities are particularly encouraged.

Correspondence and inquiries may be directed to:

Dr. David Lavrin

Immunology Program Administrator

Biology of Aging Program

National Institute on Aging

Gateway Building, Room 2C231

Bethesda, MD  20892

Telephone:  (301) 496-6402


This program is described in the Catalog of Federal Domestic Assistance

No. 93.855.  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.


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