Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute on Aging (NIA)

Funding Opportunity Title
Transformative Artificial Intelligence and Machine Learning Based Strategies to Identify Determinants of Exceptional Health and Life Span (R21/R33 Clinical Trial Not Allowed)
Activity Code

R21/R33 Phased Innovation Award

Announcement Type
Reissue of RFA-AG-22-022
Related Notices

NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022

Funding Opportunity Announcement (FOA) Number
Companion Funding Opportunity
Assistance Listing Number(s)
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) invites applications seeking to develop novel, transformative artificial intelligence/machine learning (AI/ML) strategies and computer automation to integrate, extract, and interpret multi-omic (i.e., genome, epigenome, transcriptome, proteome, metabolome, microbiome, phenome) data sets from human exceptional longevity (EL) cohorts and multiple non-human species that display a wide variation in life span, and to decipher the relationships between DNA, RNA, proteins, metabolites, and other cell variables, as well as links to disease risks and exceptionally healthy aging. The investigative team(s) for this FOA is/are expected to be multi-disciplinary, encompassing expertise in AI/ML and a variety of disciplines, including, but not limited to, aging biology, comparative biology, and bio/chemo informatics. This FOA utilizes the National Institutes of Health's (NIH) Phased Innovation Award (R21/R33) activity code. During the R21 phase, investigative teams will design and develop intelligent and innovative algorithms and novel AI/ML based computational strategies. During the R33 phase, teams will apply the developed AI/ML tools to complex, heterogenous multi-omic data sets from exceptional healthy aging human cohorts and non-human species to discover novel protective molecular factors that influence EL, and to develop translational strategies on omic-based therapeutic target(s) to prevent or delay age-related diseases, including Alzheimer’s disease (AD) and AD-related dementias (ADRD), and enhance human health span.

EL, as illustrated by the lower incidence and delayed onset of age-related disabilities/diseases (e.g., cardiovascular disease, AD, and cancer), represents an extreme phenotype, and the ability to achieve such an exceptional health span is likely to be influenced by differing domain-specific factors that affect preservation of performance in individual physiologic systems (e.g., respiratory, cardiovascular, immune) or functional domains (e.g., mobility, cognition), as well as biological processes that span those systems. EL is believed to be influenced by inherent protective molecular factors in exceptionally long-lived individuals, biological process(es), and interlayer regulatory mechanism(s) that govern the exceptional aging process. This FOA strongly encourages collaboration, coordination, and data and resource exchange among researchers studying EL (including between public-private partnerships), as well as with related NIH-supported omics activities being pursued in different cohorts, such as Trans-Omics for Precision Medicine (TOPMED), Accelerating Medicines Partnership-AD (AMP-AD), and the AD Sequencing Project (ADSP). Prospective applicants are strongly encouraged to contact the agency contacts of the National Institute on Aging (NIA) listed in Section VII to discuss their proposed projects to ensure their responsiveness to this FOA.

Key Dates

Posted Date
June 22, 2022
Open Date (Earliest Submission Date)
September 21, 2022
Letter of Intent Due Date(s)

September 21, 2022

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
October 21, 2022 November 21, 2022 Not Applicable February 2023 May 2023 July 2023

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

No late applications will be accepted for this Funding Opportunity Announcement.

Expiration Date
October 22, 2022
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the FOA) 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.

Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description


The advent of high-throughput technologies has prompted world-wide efforts to generate multi-omics data that encompasses the genome, transcriptome, proteome, metabolome, epigenome, and microbiome for millions of individuals across different populations in order to understand human health and disease etiology. This includes multi-omic data acquisition undertaken by ongoing exceptional longevity (EL) studies supported by the National Institute on Aging (NIA) that aim to identify and translate protective molecular factors and biological processes that promote exceptional health and life span. Such NIA-supported studies include the Long Life Family Study (LLFS), Longevity Consortium (LC), and Integrative Longevity Omics (ILO). While these human cohorts, with extensive physiologic, clinical, and pharmacologic data, provide advantages to unravel exceptional aging processes, the limited signal strength caused by modest variance in life span across humans and other stochastic factors, such as environmental exposures, could hinder the detection of protective biological factors that drive EL. In an effort to overcome this limitation, studies funded under this Funding Opportunity Announcement (FOA) will support comparative analyses of EL between human and non-human species for the purpose of discovering factors that contribute to increased lifespan and health span. Integrating human and non-human data is believed to yield novel insights in the exceptional aging process for the discovery of therapeutic targets and development of interventions for human health and life span.

Thus far, EL studies in humans have revealed the existence of a strong relationship between EL and exceptional health span and, specifically, aging mechanisms influencing both longevity and the development of multiple age-related conditions. For example, studies that show an association between FOXO3A andApoE2 to EL have consistently been replicated in humans, and preliminary transcriptomic and proteomic analyses in EL cohorts have revealed novel signatures of genes and proteins associated with longevity. Additionally, hypothesis-driven candidate gene association studies, based on findings from model organisms, have identified variants associated with longevity and decreased mortality rates in humans, including variants near lipoprotein metabolism genes, APOE, FOXO, insulin/IGF1 signaling pathway genes, LMNA, RNA editing genes, and HSF227.

A deeper understanding of gene/variant-protein networks is essential for the identification of potential therapeutic approaches and interventions. However, translation of genetic findings into compelling drug targets for health and life span has been difficult and ineffective, mainly due to the lack of knowledge regarding the causality and mechanistic action of protective variants of gene(s)/proteins at the physiologic level. For example, the current practice of a layered post-analysis data integration approach, wherein different omics data sets are first analyzed in isolation and then key features are “networked” or stitched together through the synthesis of significant features at joint nodes in an overall model pathway, conceals hidden interlayer mechanisms and fails to provide a comprehensive view of the causal mechanistic pathway(s) of genes/variants. Since the divergent multi-omic layers of cells, starting from genome to lipidome, are highly intertwined and regulate biological processes involving a multitude of interactions between the layers, moving from a single- to a multi-dimensional integrated view of the cellular omics with novel computational tools and strategies could provide a more holistic view of biological processes, untangle the interdependence of regulatory layers represented by various omics data and their influence over global biological networks/pathways, and, eventually, identify key factors and modules underlying the healthy aging process. However, integrated analysis of such multi-layered data is exceptionally difficult to perform, and data are difficult to interpret. Thus, alternative machine-based analytical strategies are needed to integrate multiple layers of cellular information in order to begin unraveling the causality and mechanistic action of factors that impact EL.

While the field of integrative omics is promising, it is still in its infancy and is challenging due to the heterogeneity of sources and volumes, high dimensionality, and complexity of multi-omic data and lack of computational tools for dimensionality reduction and integration among humans and other species. Hence, there is a critical need for novel, machine intelligence-based, transformative, analytical, and predictive tools, along with adequate strategies to integrate or triangulate the information resulting from different longevity omics studies in order to help solidify the role of a gene(s) or molecular pathway(s) in the expression of an EL phenotype. With artificial intelligence/machine learning (AI/ML) at the cusp of a new world of AI/ML-Biomedicine that may drive transformative progress in the discovery of predictive biomarkers and medical diagnoses, the medical field is facing a paradigm shift. As such, the development of transformative, modern AI/ML methodologies are of particular interest to EL studies in order to to maximize the potential of existing and new data for deriving novel biological concepts in aging research. The development of these AI/ML methods is expected to enable new directions for translational longevity research and may lead to important insights regarding exceptionally healthy individuals and aging.

Research Objectives

This FOA supports the development of novel, transformative, and efficient AI/ML strategies by an interdisciplinary team with specific expertise in AI/ML and aging biology to integrate, extract, and interpret genetics and multi-omic (i.e., genome, epigenome, transcriptome, proteome, metabolome, microbiome, phenome) data sets from human EL cohorts and multiple non-human species in order to understand exceptional aging processes, including discovering protective molecular factors that drive the exceptional aging process. Applications that propose the development and implementation of transformative, machine based integrative analytical tools that can provide added value beyond ongoing human-based analyses will be considered responsive to this FOA. Approaches to the analysis of large numbers of data sets derived from existing EL studies that can be accessed through the Exceptional LongevIty Translational rEsources (ELITE) portal should be prioritized. This FOA supports the creation and leveraging of open-source technology and architecture. Therefore, it is expected that all noncommercial software (including source code), software documentation, hardware designs and documentation, and technical data generated under this FOA be provided to the research community in a timely manner through the ELITE Portal, an NIA-approved data repository. Consistent with findable, accessible, interoperable, and reusable (FAIR) data principles, the ELITE portal follows open-source cataloging of datasets and tools with tiered access to the EL datasets.

This FOA utilizes the National Institutes of Health's (NIH) Phased Innovation Award (R21/R33) activity code to support pilot/innovative and implementation phase activities by an interdisciplinary research team with expertise specifically in AI/ML, aging biology, comparative biology, systems biology, and bio/cheminformatics. The following are the objectives of this FOA:

  1. Develop and validate AI/ML strategies to harmonize and integrate genetics and multi-omics data from longevity or life span studies using existing data infrastructure.
  2. Apply the developed tools to model the relationships between DNA, RNA, proteins, metabolites, and other cell variables in order to identify protective biological processes and pathways that influence EL in humans.
  3. Identify novel predictive biomarkers of aging, drug targets, follow-up experimental translational strategies, and interventions to prevent or delay age-related diseases, including  Alzheimer's disease (AD) and AD-related dementias (ADRD).

Study Timeline and Milestones

The study must be conducted using a two-phase approach in which the first phase, the R21 phase, will be the pilot/innovative phase during which awardees will develop and evaluate novel AI/ML strategies to analyze multi-omics data across human and non-human species with data harmonization tools applicable for AI-based integrative data analyses. This will be followed by a second phase, the R33 phase, during which there will be full-scale implementation focused on applying the AI/ML tools developed during the R21 phase in order to compare and validate findings from human and non-human multi-omic data sets generated by EL studies that can be accessed through the ELITE portal. Both the R21 and R33 phases must be described in the application, each with proposed milestones. The transition from the R21 to the R33 phase will be based on completion of established milestones for the R21 phase. Applications that propose only R21 or R33 activities will not be accepted under this FOA.

R21 Activities

Priority activities of the R21 phase include, but are not limited to, the following:

  1. Assess and curate publicly available multi-omic data from longevity studies on human and non-human species.
  2. Perform data quality control and develop methods for harmonization/normalization by statistical and machine learning tools for merging different sources of data with non-uniform population stratification, scaling, and dimensionality.
  3. Evaluate and refine, if necessary, existing AI/ML strategies or develop novel methods such as (1) representation learning for unsupervised and supervised dimensionality reduction, feature selection, and feature engineering for compressing high-dimensional omics data;(2) data integration applying hierarchical, stepwise, and concatenation-based integrative analysis of multiple omics data sets to, for example, identify causal pathways from SNPs via cellular pathways to longevity outcomes; (3) transfer learning methods to train/apply ML models across species and domains; and/or (4) improve the explainability and automate the interpretation of models and results across domains.
  4. Develop implementation strategies using AI/ML tools on EL multi-omic data sets.

R33 Activities

 Activities of the R33 phase include, but are not limited to, the following:

  1. Harmonize data from multiple EL projects, the Accelerating Medicines Partnership Program® for Alzheimer's Disease (AMP-AD), the Alzheimer's Disease Sequencing Project (ADSP), and other publicly available data from longevity studies. Grantees are strongly encouraged to leverage activities similar to those in the ADSP project that are in the process of developing harmonization tools across different AD studies. Applicants may refer to FOA PAR-20-099 for more information.
  2. Perform AI/ML-based integrative analysis of multi-omic data (human and non-human) to identify causal pathways that mediate protection (e.g., from SNPs via cellular pathways) to longevity outcomes.
  3. Determine familial relationships from family-based studies, population stratification, and cross-species differences in EL.
  4. Perform integrated analysis of multi-omic data from non-human species to identify factors that slow the aging process and identify human orthologs.
  5. Identify novel predictive biomarkers of aging and drug targets.
  6. Identify pharmacological interventions by exploring publicly available drug discovery databases to prevent age-related diseases, including AD/ADRD, and promote healthy aging.

Transition from the R21 to the R33 phase:

  • An initial award for up to two years will be made for the R21 pilot phase. Completion of established milestones proposed within the application will be used to assess potential transition from the R21 to the R33 phase.
  • Prior to the end of the R21 phase, grantees will be expected to submit a package requesting transition to the R33 phase. This transition package must include a progress report describing the achievements of the R21 phase, completion of the established milestones, and plans for the R33 phase considering the activities successfully completed during the R21 phase.
  • Transition packages will be reviewed by NIA program staff. If approved, the R33 will be awarded without the need to submit a new grant application.

Transition Criteria

Criteria to determine whether the award will transition from the R21 phase to the R33 phase will include the following:

  1. Are the developed AI/ML strategies effective in harmonizing and extracting the hidden knowledge underlying a biological problem from publicly available data?
  2. Have the developed methods been validated and tested for reproducibility through replication with other publicly available datasets?
  3. Is there evidence to suggest that the developed tools perform better than the existing AI/ML approaches on smaller sample sets?

All resources, tools, and findings from the awarded studies will be deposited in a NIA-designated biorepository that will include an NIA ELITE portal. The portal is currently being created and will be accessible to the public once completed.

Annual Meeting of the R21/R33 Awardees

All grantees are required to participate in an annual, one-day programmatic meeting to discuss project/technical progress and foster collaborations among the Principal Investigators (PIs), scientific staff, and other project personnel. Applications must include a budget for travel to Bethesda, Maryland for this meeting. The annual meetings are open to investigators supported under this FOA and to NIA extramural staff.

Pre-application Webinar

A planned webinar will be open to all prospective applicants to provide them the opportunity to ask questions related to the scientific scope of this FOA and technical details for applying Prospective applicants are encouraged to submit their questions regarding the FOA in advance of the webinar. Further details on where to submit the questions will be provided once the webinar has been scheduled. Participation in the webinar is not a prerequisite to applying to this FOA, but prospective applicants will need to register in order to participate. Please visit NIA's webpage for pre-application information specific to this FOA for further details regarding the webinar.

Prospective applicants are urged to consult with NIA staff listed in Section VII of this FOA early in the pre-submission process to ensure that applications are responsive to the programmatic goals of this FOA.

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

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Funds Available and Anticipated Number of Awards

NIA intends to commit $750,000 in fiscal year 2023 to fund 4 awards.

Award Budget

Application budgets are not to exceed $150,000 in direct costs per year in the R21 phase and $350,000 in direct costs per year in the R33 phase.

Award Project Period

The maximum project period is 5 years in total. The R21 phase may take up to 2 years and the R33 phase may take up to 3 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Local Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Government

  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession


  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
Foreign Institutions

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

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

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

Required Registrations

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 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 full SAM and registrations; 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.
  • – Applicants must have an active SAM registration in order to complete the 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.

Eligible Individuals (Program Director/Principal Investigator)

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.

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 FOA 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 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 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, Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. 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:

Nalini Raghavachari, Ph.D.
National Institute on Aging (NIA)
Phone: 301-496-6942

Page Limitations

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

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

For this FOA, a multi-PI arrangement with an interdisciplinary research team with expertise specifically in AI/ML, aging biology, comparative biology, systems biology, and bio/cheminformatics is required.

R&R Budget

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

Applicants must include travel funds for an annual, in-person meeting in the Washington, D.C./Bethesda, MD area with all the PIs involved in the study.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: Applicants must describe and clearly demarcate the specific aims and milestones for both the R21 and R33 phases of the proposed project. Applicants must evaluate the efficiency of, and fine tune the existing, computational tools available for integrative data analysis on genetics and multi-omics data and describe the need for developing newer methodologies. Proposed milestones should not be a restatement of the specific aims.

Research Strategy: Applicants must provide a rationale to justify the significance of the selected methodologies and computational strategies proposed for identifying profiles associated with the exceptional aging process. Describe the goals and research approach, including milestones, for both phases of the proposed project and distinguish clearly between the two phases. Applicants must describe any innovative aspects of the approach.

Applications must include milestones specific to the proposed project that will be reached by the end of the R21 phase. Metrics to assess achievement of these milestones to transition to the R33 phase should be fully explained in the application.

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.

The following modifications also apply:

In keeping with NIA/NIH's goal to enhance the transparency of reporting and enable reproducible and translatable discovery research, grantees will be required to make all data, analytical methods, network models, and research tools available to the broad scientific community prior to publication. To this end:

  • All resources (e.g., databases) and computational tools must be made accessible and reusable by qualified individuals other than the original data generators to enable data analysis and interpretation.
  • All analytical methodologies must be made fully reproducible and transparent so that results can be vetted and existing analysis techniques can be quickly applied to new application areas.
  • All models of biological systems and networks must be made open to users such that theoretical predictions can be rapidly validated experimentally.
  • All applications, regardless of the amount of direct costs requested for any one year, must address the following Resource Sharing Plans: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
  • All the resources, tools, and findings from the awarded studies must be deposited in a NIA-designated biorepository. The biorepository will include a NIA ELITE portal that is currently being developed and will be shared publicly upon completion.
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) 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 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.

PHS Assignment Request Form

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

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 (the online portal to find and apply for grants across all Federal agencies). 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 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 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.

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) must include their eRA Commons ID in the Credential fieldof 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. See Section III of this FOA for information on registration requirements.

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.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the National Institute on Aging (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 Referral Office by email at when the application has been submitted. Please include the FOA 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. Any instructions provided here are in addition to the instructions 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.

For this particular announcement, note the following:

The R21/R33 phased innovation grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. An R21/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data.  Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding.  Reviewers will assign a single impact score for the entire application, which includes both the R21 and R33 phases.

Overall Impact

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).

Scored Review Criteria

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.


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?


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?

How multidisciplinary is the expertise of the investigative team, especially in terms of AI/ML, comparitive biology, bio/chemoinformatics, systems biology, and aging biology? How likely is this expertise to aid in achieving the proposed aims of the project?


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?

How novel are the improvements to previously established methods?


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?

Are the milestones specified by the applicant realistic and appropriate for the proposed project? Will the proposed project lead to novel methodologies that could identify omics profiles associated with health and life span?

How justified are the selected methodologies and computational strategies for identifying profiles associated with exceptional aging process?

Are the following Resource Sharing Plans reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS)?


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?

Additional Review Criteria

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 Animal Section.


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.


For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.


Not Applicable


For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations

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).

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.

  • 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.

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

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

Applications will be assigned to the National Institute on Aging. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. 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.5. 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 FOA 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: Recipient 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.

2. Administrative and National Policy Requirements

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:

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 must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see and

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 FOA.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at 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.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

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 FOAs 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 on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, 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 75 – Award Term and Conditions 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.

Application Submission Contacts

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: (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: (preferred method of contact)
Telephone: 301-637-3015 Customer Support (Questions regarding registration and Workspace)
Contact Center Telephone: 800-518-4726

Scientific/Research Contact(s)

  We welcome inquiries concerning this FOA from potential applicants. Please direct all inquiries to all three program officers listed below:

Nalini Raghavachari, Ph.D.
Division of Geriatrics and Clinical Gerontology (DGCG)
National Institute on Aging (NIA)
Phone: 301-496-6942

Leonid Tsap, Ph.D.
Division of Aging Biology (DAB)
National Institute on Aging (NIA)
Phone: 301-827-4474

Marilyn Miller, Ph.D.
Division of Neuroscience (DN)
National Institute on Aging (NIA)
Phone: 301-496-9350

Peer Review Contact(s)

Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Phone: 301-402-7700

Financial/Grants Management Contact(s)

Jeni Smits
National institute on Aging (NIA)
Telephone: 301-827-4020

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.

Authority and Regulations

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.

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