Studies of Cytosolic DNAs in the Interactions of Aging Hallmarks (R01 Clinical Trial Not Allowed) | RFA AG 23 015

Opportunity Information: Apply for RFA AG 23 015

The National Institutes of Health (NIH) funding opportunity titled "Studies of Cytosolic DNAs in the Interactions of Aging Hallmarks (R01 Clinical Trial Not Allowed)" (Funding Opportunity Number RFA-AG-23-015; CFDA 93.866) supports basic and mechanistic research focused on how cytosolic DNA and cytosolic DNA-sensing pathways influence the biology of aging. The central theme is that DNA found in the cytosol, whether originating from the nucleus, mitochondria, viruses, or damaged cellular compartments, can trigger innate sensing mechanisms and downstream signaling that may intersect with multiple "hallmarks of aging." NIH is seeking projects that move beyond descriptive observations and instead explain, in detail, the molecular and cellular mechanisms by which cytosolic DNAs shape aging processes, contribute to aging-related decline, or potentially influence longevity and healthspan.

The scientific goal of the FOA is to build an in-depth understanding of how cytosolic DNA sensing mechanisms drive interactions among aging hallmarks. In practice, this means proposals should explore how cytosolic DNA appears, persists, and is detected within cells during aging, and how that detection changes key aging-relevant pathways such as inflammation and immune activation, cellular senescence, genomic instability and DNA damage responses, mitochondrial dysfunction, altered intercellular communication, epigenetic changes, proteostasis stress, stem cell exhaustion, and other widely cited hallmarks. A strong application would typically connect cytosolic DNA sensing to concrete mechanistic links between two or more hallmarks, showing how one hallmark can amplify or suppress another through cytosolic DNA-mediated signaling. The FOA is also explicitly aimed at generating insights that can help address unresolved mechanistic questions about why and how hallmark interactions produce aging phenotypes and aging-related diseases, rather than simply cataloging associations.

This opportunity uses the NIH R01 grant mechanism, indicating support for substantial, multi-year research programs with clearly defined aims, rigorous experimental strategies, and strong justification for feasibility and impact. It is labeled "Clinical Trial Not Allowed," which means the supported work must not include clinical trials as defined by NIH, so the emphasis is on preclinical, mechanistic, and experimental studies (for example, cell-based systems, animal models, human biospecimens analyzed in non-interventional ways, or other translationally relevant approaches that do not meet the NIH definition of a clinical trial). The FOA encourages innovative and mechanistic approaches, which can include development or application of new tools to track cytosolic DNA, dissect sensing pathways, or map downstream signaling consequences that affect healthspan and longevity-related biology.

Eligibility is broad and includes many types of applicant organizations. In addition to standard U.S. academic and research institutions, eligible applicants include state, county, city or township governments, special district governments, independent school districts, federally recognized tribal governments, and tribal organizations that are not federally recognized tribal governments. Eligible entities also include public housing authorities/Indian housing authorities, nonprofits with or without 501(c)(3) status (excluding institutions of higher education in those nonprofit categories), private institutions of higher education, for-profit organizations (other than small businesses), and small businesses. The FOA also highlights expanded categories of "other eligible applicants," such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), 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. entities (foreign organizations). This breadth signals NIH interest in attracting diverse scientific perspectives and institutional participation, including from institutions serving underrepresented populations and from international organizations capable of contributing unique expertise.

Key administrative details in the provided source information include that the opportunity is categorized as discretionary funding, uses the grant funding instrument, and falls under the health funding activity category. The original closing date listed is October 11, 2022, and the FOA creation date is February 25, 2022. The award ceiling and expected number of awards are not specified in the excerpt provided, which is common for some NIH announcements where budgets and award counts may depend on application pressure, scientific merit, and available appropriations. Overall, the FOA is designed to fund rigorous, mechanistic aging biology research that clarifies how cytosolic DNA sensing contributes to the interconnected network of aging hallmarks and, ultimately, to the regulation of healthspan and longevity.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Studies of Cytosolic DNAs in the Interactions of Aging Hallmarks (R01 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 2022-02-25.
• Applicants must submit their applications by 2022-10-11. (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.

Apply for RFA AG 23 015

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