Aging Mammalian Tissues In Vitro (R21 Clinical Trial Not Allowed) | RFA AG 26 014

FAQs: Aging Mammalian Tissues In Vitro (R21 Clinical Trial Not Allowed) (RFA-AG-26-014)

What is the purpose of this NIH funding opportunity?

This opportunity supports exploratory, early-stage research to build and refine sophisticated 3D in vitro microphysiological systems (MPS) that can model mammalian aging. The emphasis is on developing lab-based tissue and organ models that reproduce key aging processes and measurable aging-related phenotypes commonly observed in living organisms, with the broader aim of improving aging-mechanism research and preclinical drug discovery.

What kinds of research projects are a good fit for this NOFO?

Projects are expected to focus on creating or improving 3D MPS platforms (for example, tissue chips, organs-on-chips, or tissue organoids) that go beyond basic biology and capture aging-relevant processes and phenotypes. The intent is to push toward robust, reproducible, biologically meaningful systems that the broader aging research community can adopt for mechanistic studies and translational applications.

What does NIH mean here by microphysiological systems (MPS)?

In this announcement, MPS refers to engineered 3D in vitro platforms such as tissue chips, organs-on-chips, and organoids designed to model tissue- and organ-level biology. The expectation is that these systems can be engineered and measured in ways that help reproduce and quantify aging-related changes rather than only general cell function.

Is the NOFO focused on human-based systems or nonhuman systems?

The primary focus is on MPS made from human cells. Nonhuman mammalian cell-based systems can still be acceptable in specific roles, such as benchmarking against human systems, validating that the platform behaves as intended, or when the applicant provides a clear rationale for why the nonhuman model is directly informative for understanding human aging biology.

Are organoids, tissue chips, and organs-on-chips all within scope?

Yes. The opportunity explicitly describes platforms such as tissue chips, organs-on-chips, and tissue organoids as examples of the types of MPS that are of interest, particularly when they are engineered to reproduce aging processes and measurable aging phenotypes.

What is the central technical and biological expectation for the models?

The models should reproduce key aging processes and measurable aging-related phenotypes typically observed in living organisms. In other words, the system should enable credible, quantifiable readouts of aging biology, not simply resemble tissue structure or baseline function.

How does this opportunity relate to drug discovery and preclinical testing?

One of the stated motivations is to improve drug discovery by providing better preclinical testing platforms than traditional cell culture systems. The NOFO is positioned as a push toward more realistic, human-relevant aging models that could serve as improved testbeds for interventions.

What funding mechanism is being used?

This opportunity uses the NIH R21 mechanism, which is intended for high-risk, high-reward exploratory projects that are still at a conceptual or early developmental stage.

Is preliminary data required for an R21 application under this NOFO?

No. A key implication of the R21 mechanism as described here is that preliminary data are not required, lowering the barrier for innovative approaches that have not yet been extensively validated.

Are clinical trials allowed under this announcement?

No. Clinical trials are explicitly not allowed, and the work is not intended to be clinical research.

What does "Clinical Trial Not Allowed" practically mean for applicants?

Based on the provided description, the proposed work should remain in the realm of in vitro platform development and related experimental studies rather than human-subjects clinical trial research. The announcement explicitly prohibits clinical trials under this NOFO.

Is a multidisciplinary team required?

Yes. A defining expectation for competitive applications is a genuinely multidisciplinary approach integrating aging biology with relevant enabling disciplines.

What disciplines does NIH expect teams to integrate?

The NOFO highlights integration of aging biology with areas such as stem cell biology, tissue and organ physiology, microfluidics, bioengineering, computational biology, pharmacology, and biostatistics. The rationale is that credible in vitro aging models require both biological insight and engineering/analytical capabilities.

Why is multidisciplinary integration emphasized so strongly?

Modeling aging in vitro is presented as not being a single-discipline problem. It requires engineering stable long-term culture environments, recreating tissue-level structure and function, capturing age-associated cellular and molecular changes, and analyzing complex multi-parameter data to support credible claims about aging phenotypes and intervention effects.

Who is eligible to apply?

Eligibility is broad across U.S.-based organizations and includes government entities, academic institutions, and non-academic research performers. The listed eligible applicants include (among others): state, county, city or township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; other Native American tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (as categorized in the announcement); for-profit organizations other than small businesses; and small businesses.

Are any additional applicant categories noted as eligible?

Yes. The announcement also notes eligibility for certain additional categories such as eligible federal agencies, faith-based or community-based organizations, regional organizations, U.S. territories or possessions, and Indian/Native American tribal governments that are not federally recognized.

Can foreign organizations apply?

No. Foreign organizations are not eligible to apply under this opportunity.

Can a U.S. organization include non-domestic components as part of its application?

No. Non-domestic components of U.S. organizations are not eligible to apply as components.

Are any international collaborations allowed at all?

Yes, within limits. "Foreign components" (as defined by the NIH Grants Policy Statement) are allowed. This means a U.S. applicant may include certain foreign collaborations or activities when they meet NIH policy definitions and requirements, even though foreign organizations cannot apply as the primary applicant.

What is the funding instrument and activity category?

The funding instrument is a grant. The activity category is health, and the CFDA listing provided is 93.866.

What is the opportunity number and title?

The opportunity is titled "Aging Mammalian Tissues In Vitro (R21 Clinical Trial Not Allowed)" with the identifier RFA-AG-26-014.

When is the closing date?

The original closing date listed in the provided information is 2025-10-20.

When was this opportunity created?

The opportunity was created on 2025-08-26.

Does the provided information state an award ceiling or the expected number of awards?

No. The provided source text does not specify an award ceiling or the expected number of awards, and it indicates those details may be posted elsewhere in the full announcement or NIH budget guidance for the R21 mechanism.

What is NIH trying to achieve overall with this program?

The program is described as an NIH push toward next-generation, human-relevant experimental systems that can reproduce meaningful aspects of aging in a controlled, engineered setting. The intent is to make aging biology easier to measure, manipulate, and translate into therapeutic discovery, while encouraging interdisciplinary teams that can build platforms credible and usable by others.