Part 1. Overview Information

Key Dates

No late applications will be accepted for this Notice of Funding Opportunity.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

The identification of genetic and other factors contributing to longevity, as well as the pathways/mechanisms mediating their effects on health and life span, could lead to the development of new interventions to promote healthy aging. Since longevity is associated with diminished risk for a variety of conditions, the identification of potential therapeutic targets based on protective genetic and other factors could be especially valuable for the development of novel interventions against multiple conditions versus any single disease. Recognizing that the study of genes/protective factors associated with human healthy aging and longevity requires a broad understanding of genetic, epidemiologic, and biological principles as well as interdisciplinary interactions among investigators in these areas, the National Institute on Aging (NIA) established the cooperative agreement (U19) project known as the Longevity Consortium (LC) in 2004. The LC is part of an ongoing group of NIA-supported human longevity translational projects. Each of these projects employs different and complementary approaches for the identification and translation of protective factors (genomic and other) associated with exceptional longevity.

In Phase I, the LC focused on the identification of common genetic variants and genes in candidate pathways associated with exceptional life span in long-lived individuals (i.e., >90 years old) and in long-lived mice using association-based approaches on data from large epidemiologic populations to detect mild to moderate effects of common alleles and environmental factors on healthy survival. Additionally, the LC investigators formed cross-disciplinary collaborations focused on identifying single nucleotide polymorphisms (SNPs) in insulin-signaling pathways in association with exceptional survival, correlating telomere length with exceptional survival and the effects of growth hormone and insulin signaling in lifespan determination in mouse models, and identifying genetic variants associated with cellular stress resistance and longevity in wild-type mice. These research activities provided the groundwork for subsequent phases of the LC which incorporated extended data mining/pathway analysis for novel genetic factors as well as replication and validation of previously identified variants.

A major emphasis of the LC during Phase II, initiated in 2009, was on the translation of findings from genomics and genetic epidemiology. In particular, the identification of potential therapeutic targets based on functional pathways for longevity-associated gene variants, especially the well replicated FOXO3A and ApoE2. The LC organized working groups focused on FOXO3A and ApoE2 to generate ideas and collaborated with investigators outside of the consortium to support pilot functional studies of these variants. Examples of pilot functional studies included association studies of FOXO3 variants and aging phenotypes; an investigation of ~200 compounds that induced nuclear translocation of FOXO3 in mammalian cell lines to modify aging in C. elegans; the development of ApoE2 mimetics and testing them for anti-inflammatory and anti-cancer activity; and the examination of ApoE2 to enhance lipid efflux from astrocytes more effectively than other ApoE isoforms.

In Phase III, initiated in 2014, the LC shifted its focus to studies of centenarians, cross-species studies, and integrated data analyses, along with novel drug discovery approaches. Such approaches led to the discovery of genetic signatures of exceptional longevity based on combinations of 281 genetic variants. This discovery resulted in the development of new statistical methods in genetic epidemiology, methods for integrative analyses to determine the replicability of genetic risk scores, analyses of Alzheimer’s disease associated factors, and assessments of ancestry, but had limited translational success. The lack of an understanding of mechanistic/casual pathways by which previously identified longevity-associated variants and genes exert their effects prompted the LC to shift its focus in its current phase, Phase IV, initiated in 2019. The focus of Phase IV has been on the conduct of transcriptomic, proteomic, and metabolomic analyses of specimens from large longitudinal cohorts that include centenarians, healthy long-lived individuals (e.g., Health Aging and Body Composition (HABC), Study of Osteoporotic Fractures (SOF), Osteoporotic Fractures in Men (MrOS), and New England Centenarian Study (NECS)) with extensive phenotypic data to help identify protective factors and pathways associated with longevity and health span. The LC has continued cross-species omics studies to identify factors that produce substantial differences in species life spans. In summary, the LC has been developing strategies sequentially for the identification of targets based on variation in longevity within the human population and across multiple vertebrate taxa, and has progressed from epidemiologic and genetic studies to its current translational efforts that apply omics and cheminformatics methods to its epidemiologic and genetic data in order to find targetable pathways and drugs that could enhance human health span.

Research Objectives for Phase V

The purpose of this Notice of Funding Opportunity (NOFO) is to solicit a cooperative agreement (U19) application for the renewal of the LC. The continuation of the LC must have five main objectives:

1. Evaluate the predictive value of human biologic factors for human longevity and related aging outcomes, relationships of differing contexts to predictive value of these factors, and the biological mechanisms that account for predictive relationships.
2. Evaluate the predictive value of cross-species differences in specific biologic and genetic factors for differences in species life span.
3. Clarify the relationships between factors related to exceptional longevity in humans and factors influencing cognitive function in old age and risk or severity of Alzheimer’s disease and related dementias.
4. Assess the potential value of predictive factors for developing or repurposing drugs or other interventions to extend life span or health span. For factors with sufficient potential translational value, conduct studies to identify therapeutic targets and interventions, using defined milestones to guide decisions on their continuation or discontinuation.
5. Develop methods to increase interoperability of varied data types from differing human studies and comparative species studies and use these methods in integrative analyses combining data from multiple sources to improve understanding about factors influencing longevity and health span in differing contexts and their potential for development of interventions.

Each of these objectives must be addressed by one or more of the specific aims of the proposed U19 Cores and/or projects.

Examples of activities related to the above objectives include, but are not limited to, the following:

Objective 1

• Analyses of human genetic, multi-omic, and phenotypic data to identify predictive factors or multicomponent profiles for exceptional longevity or low risk for mortality related to specific conditions in old age.
• Analyses of effects of differing contexts that may affect levels of such predictive factors and/or the strength and direction of predictive relationships (e.g., in men vs. women, in populations with differing genetic backgrounds, age ranges, risk levels for specific aging-related diseases, or differing ethnicities). At a minimum, the project must assess differences in major U.S. ethnic groups.
• Cellular function studies to elucidate mechanisms and pathways mediating the relationships between predictive factors and longevity or low risk of age-related conditions including Alzheimer’s disease and/or related dementias, using resources such as induced pluripotent stem cells, isogenic cell lines comparing differing alleles in longevity-related genes, or organoid cultures.

Objective 2

• Comparative analyses of genetic, multi-omic, and phenotypic data in species of differing life spans to identify factors related to differences in species life spans within individual taxa and/or across multiple taxa.
• Analyses of relationships of evolutionary genomic structural variations (e.g., gene duplication or loss, evolution of new genes, or differences in synthetic blocks, to differences in species longevity within individual taxa and/or across multiple taxa.
• Studies to elucidate the bases for cross-species correlations between species life spans and ages of other life-history events (e.g., sexual maturation).

Objective 3

• Analyses of relationships of longevity-related factors to risk for Alzheimer’s disease and to maintenance of cognitive abilities throughout advanced age.
• Analyses of relationships of individual Alzheimer’s disease genetic risk factors to longevity and other health outcomes in advanced age.
• Assessment of known and potential Alzheimer’s disease risk factors predictive value in extreme old age for incidence or severity of Alzheimer’s disease or related dementias

Objective 4

• Compilation and comparison of findings on predictive factors for longevity or low risk of specific conditions in old age to identify compounds and/or therapeutic targets for intervention development or repurposing.
• For selected compounds or targets, implementation of sequential therapeutic development strategies, applying go/no go criteria for successive steps. Strategies may use database analyses and biologic studies to assess potential human effects, inform decisions about target populations and indications for use, and assess candidate interventions potential safety, efficacy, and incremental benefits beyond those of existing interventions.

Objective 5

• Development of analytic tools and informatics resources to allow combining data from pertinent human studies whose populations may vary in age and other demographic features, and which differ in study methods, and use these tools and methods to increase clarity about factors predicting longevity and risk of age-related diseases.
• Development of methods to enhance the value of cross-species genetic comparisons in elucidating genetic bases for species life span differences, including the role of evolutionary structural changes, and clarifying orthologous and paralogous relationships in genetic and gene-expression studies.
• Integrative analyses combining human and nonhuman data to clarify the effects on longevity related to interspecies differences (including differences between humans and other species) and those related to differences among humans.

These activities may be supported by Research Projects and by Resource Cores. The renewal application may propose to expand existing LC components or create new cores and projects to address the requirements of this NOFO.

An Administrative Core and an Integrative Analysis Core are required:

• The Administrative Core must conduct activities such as, but not limited to, documenting the project’s activities and schedules, coordinating meetings, providing a platform for easy access to information on study activities and data, coordinating use and sharing of data and biospecimens, and managing project finances.
• The Integrative Analysis Core will provide analytic support and development of methods, as needed, to integrate and/or harmonize data and methods for activities directed at all five project objectives.

Non-Responsiveness Criteria

The following types of applications will be considered non-responsive and will be withdrawn prior to review:

• An application that does not address each of the five main objectives by one or more of the Specific Aims of the proposed project. Each Specific Aim must address at least one of the main objectives.
• An application that does not include analyses of relationships of potential predictive factors to longevity and related outcomes in individual major U.S. ethnic groups.
• An application that does not include an Administrative Core and an Integrative Analysis Core.
• If support for pilot studies is proposed, the application that does not describe processes to identify possible pilot studies and data analyses, review their quality and priority, and assess progress of studies/analyses that are selected for support.

Additional Guidance

Successful research activities conducted by the LC project are expected to have the following:

• Success with outreach and enrollment efforts and/or leveraging of extant cohorts to increase the racial/ethnic representation in cohorts of long-lived/centenarian populations.
• Extent and quality of studies to find additional factors related to longevity and conduct of functional studies to advance discovery of novel therapeutic targets for healthy aging.
• Expansion/increases in the number of methods developed for integrative analysis (including development of new analytical tools) of multi-omics data from humans and/or across species of varying life spans.
• Success with actively developing and extending resources and actions to make research resources available to the research community via NIA’s Exceptional LongevIty Translational rEsources (ELITE) Portal. Activities might include newly developed analytical tools, a catalogue of genetic functional variants associated with longevity, the listing of other relevant translational research resources/projects, and the generation and sharing of research resources (e.g., data, biospecimens (non-human and human). This includes initiation of new collaborative efforts to advance data analysis and/or translation/target identification efforts as opportunities arise.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Only those Institutions who have previously received a sub-award/award for the Longevity Consortium U19 project are eligible to submit an application in response to this NOFO.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this NOFO. See the administrative office for instructions if planning to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this notice of funding opportunity to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Chhanda Dutta, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-4161
Email: Duttac@mail.nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required; maximum of 1
• Integrative Analysis Core: required; maximum of 1
• Additional Cores: optional; maximum of 4
• Research Project: required; maximum of 8

Overall Component

When preparing the application, use Component Type Overall .

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project/Performance Site Locations (Overall)

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research and Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this NOFO) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Specific Aims:

The Specific Aims section should include a description of how the aim relates to one or more of the five primary study objectives described below:

1. Evaluate the predictive value of human biologic factors for human longevity and related aging outcomes, relationships of differing contexts to predictive value of these factors, and the biological mechanisms that account for predictive relationships.
2. Evaluate the predictive value of cross-species differences in specific biologic and genetic factors for differences in species life span.
3. Clarify the relationships between factors related to exceptional longevity in humans and factors influencing cognitive function in old age and risk or severity of Alzheimer’s disease and related dementias.
4. Assess the potential value of predictive factors for developing or repurposing drugs or other interventions to extend life span or health span. For factors with sufficient potential translational value, conduct studies to identify therapeutic targets and interventions, using defined milestones to guide decisions on their continuation or discontinuation.
5. Develop methods to increase interoperability of varied data types from differing human studies and comparative species studies and use these methods in integrative analyses combining data from multiple sources to improve understanding about factors influencing longevity and health span in differing contexts and their potential for development of interventions.

Research Strategy:

Approach: Include the major approaches and studies involved in the application. Describe how the proposed Cores and Projects of the LC complement each other or are interdependent, and contribute to the coherence of the overall U19 study.

Renewals: Follow the directions in the SF 424 Application Guide, and provide a Progress Report (with citations) using the Significance, Innovation, and Approach sections as appropriate. Describe findings that are particularly significant in this Overall Research Plan.

Resource Sharing Plan:
Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

• Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form (Overall)

All instructions in the SF424 (R&R) Application Guide must be followed.

Administrative Core

When preparing your application, use Component Type Administrative Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Core
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Administrative Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Administrative Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Administrative Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

The Administrative Core budget may request up to $300,000 direct costs per year for pilot studies (e.g., Translational Opportunity Funds).

PHS 398 Research Plan (Administrative Core)

Specific Aims: The Administrative Core must conduct activities such as, but not limited to, documenting the project’s activities and schedules, coordinating meetings, providing a platform for easy access to information on study activities and data, coordinating the use and sharing of data and biospecimens, and managing project finances. This section should provide a concise description of the aims for the core.

Research Strategy: The Research Strategy section should include a description of the project’s organization, how its components will interact, and its processes for reaching decisions. This section must also include a description of the design of the study’s planned assessment of predictive factors for longevity in major U.S. ethnic groups, including a description of target sample sizes and statistical power.

Significance: Describe how the activities of the Administrative Core will facilitate and support scientific integration across the components of the LC.

Approach: Applicants must describe the project’s organization, how its components will interact, and its processes for reaching decisions. Explain how the Administrative Core will be operationalized to document the project’s activities and schedules, coordinate meetings, provides platform for easy access to information on study activities and data, coordinate the use and sharing of data and biospecimens, and manage project finances. If support for pilot studies (e.g., Translational Opportunity Funds) is proposed, the application must describe processes to identify possible pilot studies and data analyses, review their quality and priority, and assess progress of studies/analyses that are selected for support.

Innovation: This section is optional.

Progress Report: Unless it is a newly proposed project, report on progress since the previous renewal.

Letters of Support: Statements of individual and Institutional Commitment, as appropriate, should be included in this section.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Informationform or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Integrative Analysis Core

When preparing your application, use Component Type Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Integrative Analysis Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Integrative Analysis Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Integrative Analysis Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Integrative Analysis Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Integrative Analysis Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Integrative Analysis Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Integrative Analysis Core)

Specific Aims: The Integrative Analysis Core will provide analytic support and development of methods, as needed, to integrate and/or harmonize data and methods for activities directed at all five project objectives. This section should provide a concise description of the aims for the Core.

Research Strategy: Organize the Research Strategy into sections on a) Significance, b) Approach, and c) Innovation.

Significance: Describe the contributions that the Integrative Analysis Core will make to the overall project.

Approach: Applicants must describe how the Integrative Analysis Core will interface with the other components and research activities of the LC. In addition, applicants must describe how integration across different data types will be achieved to clarify factors influencing cross-species differences in longevity,(including differences between humans and other species) and those related to differences among humans).

Innovation: Identify methodological/analytical approaches needed and describe how the core will develop novel analytical approaches and tools to address the methodological needs.

Letters of Support: Statements of individual and Institutional Commitment, as appropriate, should be included in this section.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Integrative Analysis Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Other Cores

When preparing your application, use Component Type Other Cores.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Other Cores)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Other Cores)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Other Cores)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Other Cores)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Other Cores)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Other Cores)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Other Cores)

Specific Aims: Applicants must Identify with which projects the proposed Core will assist and the role of the core in the overall goals of the LC.

Research Strategy: Organize the Research Strategy into sections on a) Significance, b) Approach, and c) Innovation.

Significance: Describe the contributions that the proposed Core will make to the overall project.

Innovation: This section is optional.

Approach: Applicants must describe how the proposed Core will interface with the other components and research activities of the LC.

Progress Report: Unless it is a newly proposed Core, report on progress since the previous renewal.

Letters of Support: Statements of individual and Institutional Commitment, as appropriate to the Research Project, should be included in this section.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification: Not Applicable for each component. Resource Sharing Plans should be submitted only in the Overall section only. See instructions in Overall section.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Other Cores)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

Research Project

When preparing your application, use Component Type Project.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Research Project)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Project)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Project)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Research Project)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Project)

Specific Aims: This section should provide a concise description of the aims for the research project.

Organize the Research Strategy into sections on a) Significance, b) Approach and c) Innovation.

Significance: Describe the overall goals and the impact of the science proposed in relation to the state of the field. This section should also explain the contribution of the research project to the overall goals of the LC and how the component will interact with, and benefit from, other components.

Innovation: Describe the unique and innovative contributions that will be made by this project. Explain how these contributions will be made possible by team synergy beyond the otherwise independent research projects.

Approach: Describe and offer evidence for the feasibility of the proposed experiments, the advantages of any new methodologies, the potential pitfalls and alternative approaches for the project, and how these might impact overall progress. Methods and technologies to be used by the projects must be well justified, critical, and relevant to the specific aims of the proposed projects.

Research activities and specific aims proposed by the projects should clarify relationships between factors contributing to exceptional longevity ?in humans and those related to risk or severity of Alzheimer's Disease and related dementias.

The plans proposed by the projects for evaluating the predictive value of biologic factors for longevity and related aging outcomes in humans and/or for cross-species differences must be described in sufficient detail.

Proposed studies and their rationale for assessing the potential translational value of predictive factors (e.g., identification of therapeutic targets and interventions, drug repurposing) must be discussed in adequate detail, including defined milestones to guide decisions on their continuation.

The data generated by the proposed projects must include multiple data types and address the need for data integration to clarify the effects on longevity related to interspecies differences (including differences between humans and other species) and those related to differences among humans.

Progress Report: Unless it is a newly proposed project, report on progress since the previous renewal.

Letters of Support: Statements of individual and Institutional Commitment, as appropriate to the Research Project, should be included in this section.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification: Not Applicable for each component. Resource Sharing Plans should be submitted only in the Overall section only. See instructions in Overall section.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Research Project)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how applications will be automatically assembled for review and funding consideration after submission, refer to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NIA. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIA Review Office by email at ramesh.vemuri@nih.gov when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and
2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

How well will the planned project’s organization, its plans for how its components will interact, and its processes for reaching decisions provide for effective progress toward the study’s objectives?

How adequate i’s the design of the study’s planned assessment of predictive factors for longevity in major U.S. ethnic groups, including its target sample sizes and statistical power, to characterize such factors and their relationships to longevity in these groups?

How sufficient are the plans for the Administrative Core’s activities to provide adequate coordination for study progress?

How adequate are the planned interactions of the Integrative Analysis Core with other study components for enhancing the project’s research activities?

How appropriate are the analytical approaches described by the Integrative Analysis Core to achieve integration across different data types to clarify the effects on longevity related to interspecies differences (including differences between humans and other species) and those related to differences among humans?

If support for pilot studies is proposed, how sufficient are the projects proposed processes to identify possible pilot studies and data analyses, review their quality and priority, and assess progress of studies/analyses that are selected for support, to ensure that high-quality research projects will be selected and conducted effectively?

To what extent are the proposed methods and technologies well justified, critical, and relevant to the specific aims of the proposed projects?

How appropriate and reasonable are the plans proposed by the projects for evaluating the predictive value of biologic factors for longevity and related aging outcomes in humans and/or for cross-species differences?

As applicable, how appropriate are the research activities and specific aims of the proposed projects to clarify relationships between factors contributing to exceptional longevity ?in humans and those related to risk or severity of Alzheimer's Disease and related dementias?

How detailed are the proposed studies and their rationale for assessing the potential translational value of predictive factors (e.g., identification of therapeutic targets and interventions, drug repurposing), including defined milestones to guide decisions on their continuation?

To what extent does the data generation by the proposed projects include multiple data types and address the need for data integration to clarify the effects on longevity related to interspecies differences (including differences between humans and other species) and those related to differences among humans?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIA, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO . Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council on Aging. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Prior Approval of Pilot Projects

If the renewal of the LC chooses to include the conduct of pilot studies (e.g., Translational Opportunity Funds (TOF)), then recipient-selected projects will require approval by NIH prior to initiation.

• The recipient institution will comply with the NIH Guidance on Changes That Involve Human Subjects in Active Awards and That Will Require Prior NIH Approval.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federal wide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75 and 2 CFR 200, and other DHHS, PHS, and NIH grant administration policies. .

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipient is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipient for the project as a whole, although specific tasks and activities may be shared among the awardee and the NIH as defined below.

• The Program Director(s)/Principal Investigator(s) (PD/PI(s)) will have the primary responsibility for defining the details for the projects within the guidelines of this NOFO. The PD/PI will agree to accept the close coordination, cooperation, and participation of the NIH staff (Project Scientists) in those aspects of scientific and technical management of the projects as described below.

Specifically, the PD/PI(s) supported by this LC will be responsible for the following:

• Retain the primary authority and responsibility for the project as a whole and development of the methods and procedures to accomplish the aims and objectives of the NOFO, and preparation of publications.
• Provide, in addition to standard annual progress reports, other relevant information to the NIH Project Scientist(s) or Program Officer, and coordinate and cooperate with NIH staff and other members of appropriate collaborating NIH programs.
• Work directly with the NIH Project Scientist(s) on the coordination of intra-program activities and the integration of individual longevity projects, as well as with other relevant NIH programs.
• Budget for and participate in virtual or in-person travel to Bethesda, MD for joint meetings held annually, along with other critical staff.
• Participate in the appropriate coordinating meetings and/or working groups, and/or teleconferences, as needed.
• Awardee will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• One or more designated NIH Program Staff members, acting as Project Scientists, will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The role of the Project Scientist(s) will be to facilitate and not to direct. This includes facilitating the partnership relationship between NIH, the group of ongoing translational projects on exceptional longevity and the ELITE Data Management Coordinating Center.

Specifically, the NIH Project Scientist will be responsible for the following:

• Provide technical assistance and advice to the LC awardee as appropriate to achieve the aims of the cooperative agreement.
• Promote and help coordinate collaborative efforts that involve interactions with other pertinent NIA-supported translational projects and/or resources, as well as with other NIH-sponsored programs (e.g., AMP-AD, ADSP, NCATS, TOPMed), projects, and centers where appropriate.
• Assist in the interaction between the awardee and investigators at other institutions, as appropriate for the program.
• Assist in avoiding unwarranted duplication of effort.
• To help carry out these duties, Project Scientists may consult with non-NIH experts in the field.
• The NIH Project Scientist(s) will perform the initial analysis of awardee milestones and will work with the Program Officer on any milestone negotiations.
• The NIH Project Scientist(s) will form an observational study monitoring board (OSMB) composed of senior non-federal scientists who are not directly involved in the activities of the LC to advise the NIA on the progress of the milestone deliverables, on the contributions of individual projects and/or collaborations across the EL projects.
• Additionally, an NIH Program Officer will be responsible for the normal scientific and programmatic stewardship of the awards and will be named in the award notice. In addition, the NIH Program Officer will have the option to recommend, following consultation with the NIH Project Scientist(s), the withholding or reduction of support from any project that substantially fails to achieve its goals according to the milestones agreed to at the time of the award.
• NIH reserves the right to withhold funding or curtail an award in the event of substantive changes in the project, or failure to make sufficient progress toward the work scope with which NIH concurred, or ethical or conflict of interest issues.

The NIH Project Scientist(s) and the PDs/PIs of the LC will be jointly responsible for the coordination of intra-program activities and the integration of individual projects with other appropriate NIA and NIH programs. Specifically, areas of Joint Responsibility include the following:

• Developing working groups and/or coordinating committees and trans-project efforts as needed.
• Organizing and conducting regular meetings to share progress and foster collaborations across the ongoing translational projects on human longevity, either by teleconference, videoconference, or face-to-face, as needed.
• Organizing workshops to promote outreach.
• Convene to assess progress, discuss data resources, establish priorities, consider policy recommendations, propose publication guidelines, and discuss strategies.
• Meet in person, virtually, or by teleconference, with additional project staff and/or NIH staff, on a schedule to be determined.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described. If additional Data Management and Sharing requirements need to be added, please insert what requirements are desired.

The NIA expects that resources collected/analyzed, and data generated by the LC during the renewal phase will be made broadly available to the scientific community via NIA’s Exceptional LongevIty Translational rEsources (ELITE) portal. Under the 2023 Data Management and Sharing (DMS) Policy, NIH expects researchers to maximize the appropriate sharing of scientific data, taking into account factors such as legal, ethical, or technical issues that may limit the extent of data sharing and preservation. The LC renewal application should include a detailed DMS plan, including genomic data sharing (GDS)-specific considerations within the elements of a DMS plan and describe any specific circumstances which would preclude sharing of data via the ELITE portal.

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Chhanda Dutta, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-4161
Email: duttac@mail.nih.gov

Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-402-7700
Email: ramesh.vemuri@nih.gov

Laura Pone
National Institute on Aging (NIA)
Telephone: 301-451-9956
Email: laura.pone@nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.