Opportunity Information: Apply for RFA AG 25 019
The National Institutes of Health, through the National Institute on Aging (NIA), is offering a discretionary grant opportunity titled "The Impact of Stressors on the Biological Mechanisms of Aging and Other Aging-Associated Outcomes in Experimental Model Systems" (Funding Opportunity Number RFA-AG-25-019). The core idea behind this program is that stress is a normal part of real life, but many experimental aging studies in model systems do not intentionally include well-defined stress exposures. That gap can make it harder to translate discoveries about the biology of aging (including work on interventions meant to slow aging) into insights that hold up in the messy, stress-filled conditions that humans and other organisms actually experience. This NOFO is meant to push the field toward aging studies that explicitly incorporate stressors during adulthood and then track how those stressors shape biological aging and downstream outcomes.
The research focus is on stressor exposures during the post-development period, meaning adulthood rather than early development. Applicants are expected to use clearly characterized stressors, which can include physical, social, and environmental stressors, and to specify the stressor duration, intensity, and timing. The initial goal is to determine whether adult exposure to these stressors produces measurable changes in one or more of the "hallmarks of aging" (a commonly used framework for core biological processes that drive aging). In other words, the program is not only asking whether stress is "bad" in a general sense; it is asking applicants to connect defined stress exposures to concrete, quantifiable aging mechanisms in experimental systems.
This is a phased award using the R61/R33 mechanism, and clinical trials are not allowed. The first phase (R61) is exploratory and milestone-driven, providing up to two years of support to establish feasibility and generate convincing early evidence. In this phase, teams should be able to show that their chosen stressor paradigm in adulthood can move the needle on measurable aging biology endpoints, particularly those aligned with the hallmarks of aging. The expectation is that applicants will propose clear go/no-go milestones so the NIA can evaluate whether the project is ready to progress.
If the R61 milestones are successfully met, the project may transition to the second phase (R33), which can provide up to three additional years of support. The R33 phase is intended to scale up and deepen the work by testing how the stressor(s) influence broader aging outcomes such as lifespan, healthspan, and resilience. It also encourages studying interactions between stress exposure and other influential variables, such as genotype, diet, and anti-aging or geroprotective interventions. In practical terms, this second phase is where applicants can move from mechanism-focused signals to more integrated outcomes, including whether stress changes how organisms respond to dietary patterns, genetic backgrounds, or interventions designed to slow aging processes.
The NOFO is intentionally broad about the kinds of experimental systems that can be used. Applicants may propose in vitro systems, standard laboratory animal models, or well-characterized animal populations that are wild, captive, free-ranging, or domesticated. The emphasis is less on a single favored model and more on thoughtful design, clear stressor characterization, and strong measurement strategies that link stress exposure in adulthood to aging biology and aging-associated outcomes.
Eligibility is also broad and includes many organization types: state, county, and local governments; special district governments; independent school districts; public and state-controlled and private institutions of higher education; federally recognized Native American tribal governments; tribal organizations (including those other than federally recognized governments); public housing authorities/Indian housing authorities; nonprofits (with or without 501(c)(3) status); for-profit organizations (other than small businesses); small businesses; and other entities. The announcement also explicitly calls out additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-U.S. (foreign) organizations. That breadth signals an interest in attracting diverse teams, settings, and model systems while keeping the science centered on biological aging mechanisms and experimentally defined stress exposures in adulthood.
Key administrative details provided include the NIH as the agency, the activity category of Health, and the CFDA number 93.866 (NIA-related). The original closing date listed is 2024-11-07, and awards are structured around the two-year R61 plus the potential three-year R33 continuation, contingent on NIA determination that R61 milestones were met, alignment with NIA priorities, and availability of funds. The listing does not provide an award ceiling or expected number of awards in the source data shown, which typically means applicants should rely on the full NOFO text and NIH budget guidance for practical budgeting expectations.
Overall, this opportunity is aimed at making experimental aging research more realistic and informative by embedding adulthood stress exposures directly into study designs, then tracing how those exposures alter recognized mechanisms of aging and ultimately shape lifespan, healthspan, and resilience. The program is structured to support projects that start with a tightly defined, milestone-based proof-of-concept stage and then expand into more comprehensive tests of outcomes and interactions once the initial evidence base is strong.Apply for RFA AG 25 019
- The National Institutes of Health in the health sector is offering a public funding opportunity titled "The Impact of Stressors on the Biological Mechanisms of Aging and Other Aging-Associated Outcomes in Experimental Model Systems (R61/R33 Clinical Trial Not allowed)" and is now available to receive applicants.
- Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.866.
- This funding opportunity was created on 2024-08-27.
- Applicants must submit their applications by 2024-11-07. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
- Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.
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Frequently Asked Questions (FAQs)
What is the title of this grant opportunity?
The opportunity is titled "The Impact of Stressors on the Biological Mechanisms of Aging and Other Aging-Associated Outcomes in Experimental Model Systems."
What is the Funding Opportunity Number (NOFO/RFA number)?
The Funding Opportunity Number is RFA-AG-25-019.
Which NIH Institute is offering this opportunity?
The National Institutes of Health (NIH), through the National Institute on Aging (NIA), is offering this discretionary grant opportunity.
What is the main purpose of this funding opportunity?
The purpose is to support experimental aging studies that intentionally incorporate well-defined stressor exposures during adulthood and then measure how those stressors affect biological mechanisms of aging and aging-associated outcomes. The goal is to make model-system aging research more relevant to real-world conditions where stress is common.
Why does this program emphasize stressors in experimental aging research?
The program is based on the idea that many experimental aging studies do not include clearly characterized stress exposures, even though stress is a normal feature of real life. This gap can make it harder to translate discoveries about the biology of aging and interventions intended to slow aging into insights that hold under realistic, stress-influenced conditions.
What types of stressors are relevant under this opportunity?
The NOFO allows physical, social, and environmental stressors, as long as they are clearly characterized and well defined.
Do applicants need to define the stressor conditions in detail?
Yes. Applicants are expected to specify stressor duration, intensity, and timing, and to use clearly characterized stressor paradigms.
What life stage should the stress exposures focus on?
The focus is on stressor exposures during the post-development period, meaning adulthood rather than early development.
What kinds of outcomes does the NOFO want researchers to measure first?
The initial objective is to determine whether adult exposure to defined stressors produces measurable changes in one or more "hallmarks of aging" (a commonly used framework describing core biological processes that drive aging).
Is the program asking whether stress is simply harmful in general?
No. The emphasis is on connecting defined stress exposures to concrete, quantifiable aging mechanisms in experimental systems, rather than making broad claims about stress being "good" or "bad."
What funding mechanism is used for this opportunity?
This is a phased award using the R61/R33 mechanism.
How does the phased R61/R33 structure work in this program?
The project starts in an exploratory, milestone-driven R61 phase (up to two years). If R61 milestones are successfully met, the project may transition to the R33 phase (up to three additional years) to expand and deepen the research.
How long can the R61 phase last?
Up to two years of support are available for the R61 phase.
What is expected during the R61 phase?
During R61, teams are expected to establish feasibility and generate convincing early evidence that their adult stressor paradigm can produce measurable effects on aging biology endpoints, particularly those aligned with the hallmarks of aging. Applicants are also expected to propose clear go/no-go milestones.
What are "go/no-go" milestones in the context of this opportunity?
Go/no-go milestones are predefined, milestone-based criteria used by NIA to evaluate whether sufficient progress and feasibility have been demonstrated in R61 to justify potential transition into the R33 phase.
How long can the R33 phase last?
The R33 phase can provide up to three additional years of support.
What is the purpose of the R33 phase?
The R33 phase is intended to scale up and deepen the work by testing how stressor exposure influences broader aging outcomes such as lifespan, healthspan, and resilience, and by examining interactions between stress and other influential variables.
What kinds of broader outcomes are encouraged in the R33 phase?
The NOFO highlights lifespan, healthspan, and resilience as examples of broader aging outcomes for the R33 phase.
Does the NOFO encourage studying interactions with other variables?
Yes. The R33 phase encourages examining interactions between stress exposure and variables such as genotype, diet, and anti-aging or geroprotective interventions.
Can projects examine how stress affects responses to anti-aging or geroprotective interventions?
Yes. The NOFO specifically encourages studying interactions between stress exposure and interventions designed to slow aging processes, including whether stress changes how organisms respond to such interventions.
What experimental systems are allowed under this opportunity?
The NOFO is broad and allows in vitro systems, standard laboratory animal models, and well-characterized animal populations that may be wild, captive, free-ranging, or domesticated.
Is there a single preferred model organism or experimental system?
No. The emphasis is less on a favored model and more on thoughtful study design, clear stressor characterization, and strong measurement strategies linking adult stress exposure to aging biology and aging-associated outcomes.
Are clinical trials allowed?
No. Clinical trials are not allowed under this opportunity.
Who is eligible to apply?
Eligibility is broad and includes (among others) state, county, and local governments; special district governments; independent school districts; public and state-controlled and private institutions of higher education; federally recognized Native American tribal governments; tribal organizations (including those other than federally recognized governments); public housing authorities/Indian housing authorities; nonprofits (with or without 501(c)(3) status); for-profit organizations (other than small businesses); small businesses; and other entities.
Are non-U.S. (foreign) organizations eligible?
Yes. The announcement explicitly lists non-U.S. (foreign) organizations as eligible applicants.
Does the NOFO highlight eligibility for specific institution types (for example, MSIs and similar organizations)?
Yes. The announcement explicitly calls out additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, HBCUs, TCCUs, and also mentions faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions.
What is the agency and activity category associated with this listing?
The agency is NIH, and the activity category listed is Health.
What CFDA number is associated with this opportunity?
The CFDA number provided is 93.866 (NIA-related).
What is the closing date listed for the opportunity?
The original closing date listed is 2024-11-07.
Is the R33 phase funding guaranteed if an application is awarded in R61?
No. Transition from R61 to R33 is contingent on NIA determination that R61 milestones were met, alignment with NIA priorities, and availability of funds.
Does the source information provide an award ceiling or the expected number of awards?
No. The information provided does not include an award ceiling or expected number of awards in the source data shown. Applicants are expected to rely on the full NOFO text and NIH budget guidance for budgeting expectations.
What makes a strong fit for this program based on the description provided?
A strong fit is a project that embeds well-defined adult stress exposures into an experimental aging study, measures quantifiable aging biology endpoints (especially hallmarks of aging) in the early phase, uses clear milestone-based decision points, and then expands into broader aging outcomes and interaction testing in the second phase if feasibility and early signals are demonstrated.
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