Opportunity Information: Apply for PAR 18 026
This NIH grant opportunity (PAR-18-026) is an R01 funding announcement focused on research that uses human-based systems to understand how naturally occurring FOXO3 gene variants linked to exceptional longevity influence aging-related biology, and how that knowledge could be turned into practical therapeutic target ideas for promoting healthy aging. The scope is explicitly centered on in vivo studies in humans as well as in vitro work using human cells and tissues, with the expectation that projects will connect FOXO3 longevity-associated genetics to measurable phenotypes, underlying cellular functions, and actionable pathways. The announcement is labeled "Clinical Trial Optional," meaning applicants may propose clinical trials if appropriate, but a trial is not required as long as the work fits the human-focused and translational aims.
At the core of the FOA is the idea that FOXO3 is a key node in pathways that regulate stress resistance, metabolism, and other processes thought to influence lifespan and healthspan. Rather than funding general aging studies, this program targets projects that specifically examine human FOXO3 longevity variants and the biology they affect. Therapeutic target identification is a major emphasis: the potential targets are not limited to FOXO3 itself but also include upstream regulators and downstream effectors within FOXO3-mediated signaling networks. In practical terms, proposals should aim to clarify which molecular components in these pathways are most responsible for beneficial longevity-associated effects and therefore might be good candidates for drug development or other interventions.
The FOA highlights three broad and overlapping research directions. First are studies that examine the in vivo phenotypic effects of human FOXO3 variants. These could include identifying how variant carriers differ in clinically relevant traits tied to healthy aging, such as resilience to age-related decline, cardiometabolic profiles, immune function, cognitive outcomes, frailty-related measures, or other physiological markers, as long as the work is grounded in human participants and links back to FOXO3 genotype. Second are studies that dig into how these variants change cellular functions and the pathways that mediate them, using human cells or tissues to map functional consequences, pathway activity, and mechanisms. Third are studies that move from mechanism to translation by identifying and evaluating candidate therapeutic targets, including target validation efforts and testing candidate compounds or interventions that engage FOXO3 functional pathways in ways that could plausibly mimic or leverage the protective effects seen in longevity-associated variants.
Because the stated goal is to inform therapeutic target identification and potential intervention testing for healthy aging, competitive projects would typically be expected to go beyond association and provide functional evidence. That can mean showing how a specific FOXO3 variant shifts pathway signaling, alters transcriptional programs, changes stress-response phenotypes in relevant human cell types, or influences biomarkers in variant carriers in ways that are consistent with healthier aging. Similarly, intervention-oriented projects would be expected to justify why a particular upstream regulator, downstream effector, or pathway component is a promising target, and then provide data or a plan to evaluate whether modulating it produces beneficial, FOXO3-pathway-consistent effects in human systems.
The administering agency is the National Institutes of Health, and the activity category is health (CFDA 93.866). The mechanism is an NIH R01 research project grant, which generally supports substantial, hypothesis-driven research programs. The original closing date listed in the source data is 2018-05-07, and the FOA was created on 2017-11-01; applicants would need to verify current availability, deadlines, and any reissued versions of the announcement through NIH since older FOAs are sometimes expired, updated, or replaced.
Eligibility is broad and includes many common U.S. applicant organizations such as public and private institutions of higher education, nonprofits (with and without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and various levels of government (state, county, city/township, special districts), as well as independent school districts and public housing authorities/Indian housing authorities. It also includes federally recognized Native American tribal governments and other Native American tribal organizations. The FOA also explicitly calls out additional eligible applicant types, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISISs, Hispanic-serving Institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, eligible federal agencies, U.S. territories or possessions, regional organizations, and even non-domestic (non-U.S.) entities (foreign organizations) and Indian/Native American Tribal Governments that are not federally recognized. This wide eligibility reflects NIH's interest in drawing from diverse institutional settings and populations, which can be especially relevant for studying genetic variants and aging phenotypes across different cohorts.
Overall, the opportunity is designed for teams that can combine human genetics, deep phenotyping, and functional biology in human systems to translate FOXO3 longevity variant biology into concrete therapeutic hypotheses. The most aligned applications are likely to be those that (1) start from FOXO3 variant status in humans, (2) connect that status to meaningful aging-related phenotypes and mechanistic cellular readouts, and (3) use those mechanistic insights to prioritize, validate, and possibly test interventions targeting FOXO3 or its pathway components with the long-term goal of improving healthspan.Apply for PAR 18 026
- The National Institutes of Health in the health sector is offering a public funding opportunity titled "Phenotypic and Functional Studies on FOXO3 Human Longevity Variants to Inform Potential Therapeutic Target Identification Research (R01 Clinical Trial Optional)" 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 2017-11-01.
- Applicants must submit their applications by 2018-05-07. (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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FAQs: NIH PAR-18-026 (R01) - Human FOXO3 Longevity Variants and Healthy Aging
What is the focus of this NIH funding opportunity (PAR-18-026)?
This NIH opportunity supports R01 research projects that use human-based systems to understand how naturally occurring human FOXO3 gene variants associated with exceptional longevity influence aging-related biology, and how those insights can be translated into practical therapeutic target ideas to promote healthy aging (healthspan).
What grant mechanism is used for this opportunity?
The mechanism is an NIH R01 (Research Project Grant), which generally supports substantial, hypothesis-driven research programs.
Which agency administers the grant?
The administering agency is the National Institutes of Health (NIH).
What is the activity category and CFDA number?
The activity category is health, and the CFDA number listed is 93.866.
What types of research does the FOA prioritize?
The FOA prioritizes research that is explicitly centered on human-focused approaches: in vivo studies in humans and in vitro work using human cells and tissues. Projects are expected to connect FOXO3 longevity-associated genetics to measurable phenotypes, underlying cellular functions, and actionable pathways that could inform therapeutic target identification.
Does the research have to be conducted in humans?
The scope is explicitly centered on in vivo studies in humans and in vitro studies using human cells and tissues. The emphasis is on human-based systems that link FOXO3 genotype to aging-related biology and translational target ideas.
Are clinical trials required under this announcement?
No. The FOA is labeled "Clinical Trial Optional," meaning applicants may propose a clinical trial if appropriate, but a clinical trial is not required as long as the proposed work fits the human-focused and translational aims.
Is this a general aging research program?
No. This program is targeted rather than general: it specifically examines human FOXO3 longevity variants and the biology they affect, with a strong emphasis on therapeutic target identification within FOXO3-mediated pathways.
Why is FOXO3 central to this FOA?
FOXO3 is described as a key node in pathways that regulate stress resistance, metabolism, and other processes thought to influence lifespan and healthspan. The FOA is built around understanding how longevity-associated FOXO3 variants influence these pathways in humans.
Do projects need to include therapeutic target identification?
Yes, therapeutic target identification is a major emphasis. The FOA expects projects to translate FOXO3 longevity-variant biology into actionable therapeutic hypotheses and potential intervention strategies for promoting healthy aging.
Are potential therapeutic targets limited to FOXO3 itself?
No. The FOA states that potential targets are not limited to FOXO3. They can include upstream regulators and downstream effectors within FOXO3-mediated signaling networks.
What are the main research directions highlighted in the FOA?
The FOA highlights three broad and overlapping directions: (1) in vivo phenotypic effects of human FOXO3 variants, (2) cellular functions and pathways altered by these variants using human cells/tissues, and (3) translation-focused work that identifies and evaluates candidate therapeutic targets, including validation and testing of candidate compounds or interventions that engage FOXO3 pathway biology.
What kinds of human phenotypes or traits are considered relevant?
Examples mentioned include resilience to age-related decline, cardiometabolic profiles, immune function, cognitive outcomes, frailty-related measures, and other physiological markers, as long as the work is grounded in human participants and links back to FOXO3 genotype.
What is meant by "functional evidence" in competitive applications?
The FOA indicates that competitive projects should typically go beyond association studies and provide functional evidence. Examples include showing how a specific FOXO3 variant shifts pathway signaling, alters transcriptional programs, changes stress-response phenotypes in relevant human cell types, or influences biomarkers in variant carriers in ways consistent with healthier aging.
Can in vitro experiments be included, and if so, what kind?
Yes. The FOA supports in vitro work using human cells and tissues to map functional consequences of FOXO3 longevity variants, including pathway activity, mechanisms, and cellular phenotypes relevant to aging biology.
What does the FOA expect from intervention-oriented or translational projects?
Intervention-oriented projects are expected to justify why a particular upstream regulator, downstream effector, or pathway component is a promising therapeutic target and to provide data or a plan to evaluate whether modulating it produces beneficial effects consistent with FOXO3-pathway activity in human systems.
Does the FOA require linking genetics to measurable outcomes?
Yes. Projects are expected to connect FOXO3 longevity-associated genetics to measurable phenotypes, cellular functions, and actionable pathways, tying variant status to biological and potentially clinically relevant readouts.
Who is eligible to apply?
Eligibility is broad. It includes public and private institutions of higher education; nonprofits with and without 501(c)(3) status; for-profit organizations (other than small businesses); small businesses; and various government entities (state, county, city/township, special districts), independent school districts, and public housing authorities/Indian housing authorities.
Are tribal organizations eligible?
Yes. Eligible applicants include federally recognized Native American tribal governments and other Native American tribal organizations, and it also includes Indian/Native American Tribal Governments that are not federally recognized.
Are minority-serving institutions explicitly included as eligible applicants?
Yes. The FOA explicitly calls out eligibility for Alaska Native and Native Hawaiian Serving Institutions, AANAPISISs, Hispanic-serving Institutions, Historically Black Colleges and Universities, and Tribally Controlled Colleges and Universities.
Are faith-based and community-based organizations eligible?
Yes. Faith-based or community-based organizations are explicitly listed as eligible applicant types.
Can foreign (non-U.S.) organizations apply?
Yes. The FOA includes non-domestic (non-U.S.) entities (foreign organizations) as eligible applicants.
Are U.S. territories or possessions eligible to apply?
Yes. U.S. territories or possessions are explicitly included among eligible applicant types.
When was this FOA created and what is the listed closing date?
The FOA was created on 2017-11-01. The original closing date listed in the source data is 2018-05-07.
Is this FOA necessarily still open?
Not necessarily. The provided information notes that older FOAs are sometimes expired, updated, or replaced, and applicants would need to verify current availability, deadlines, and any reissued versions through NIH.
What kinds of teams or capabilities are best aligned with this opportunity?
The opportunity is designed for teams that can combine human genetics, deep phenotyping, and functional biology in human systems, and translate FOXO3 longevity variant biology into concrete therapeutic hypotheses. The most aligned applications are described as those that (1) start from FOXO3 variant status in humans, (2) connect variant status to meaningful aging-related phenotypes and mechanistic cellular readouts, and (3) use mechanistic insights to prioritize, validate, and possibly test interventions targeting FOXO3 pathway components with the long-term goal of improving healthspan.
What is the overall goal of the research supported by this FOA?
The overall goal is to understand the biology influenced by human FOXO3 longevity-associated variants and use that knowledge to identify actionable therapeutic targets and potential interventions aimed at promoting healthy aging.
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