Mechanisms of Rejuvenation and Age-Acceleration in Heterochronic Blood Exchange (R01 Clinical Trial Not Allowed) | RFA AG 21 002

Opportunity Information: Apply for RFA AG 21 002

The NIH grant opportunity titled "Mechanisms of Rejuvenation and Age-Acceleration in Heterochronic Blood Exchange (R01 Clinical Trial Not Allowed)" (Funding Opportunity Number RFA-AG-21-002) is aimed at advancing basic and mechanistic aging research using heterochronic blood exchange (HBE) models. HBE refers to experimental setups in which blood or circulatory factors are exchanged between young and old laboratory animals, allowing researchers to observe whether and how "youthful" or "aged" traits can be transferred. The central purpose of this announcement is to support studies that dig into why these phenotype shifts happen, what specific biological components drive them, and how those components act across different tissues and cell populations.

A major emphasis of the funding is on identifying the multiple factors involved in rejuvenation or accelerated aging observed in these experiments. Rather than focusing on a single molecule or pathway, the FOA encourages research that treats the phenomenon as multi-factorial. That includes circulating proteins, metabolites, lipids, extracellular vesicles, immune mediators, and other blood-borne signals, along with the possibility that combinations of factors are required to produce measurable effects. The opportunity also stresses the importance of pinpointing which cell types and tissues respond to heterochronic exchange, reflecting an understanding that changes seen in muscle, brain, liver, heart, immune system, or stem cell compartments may be driven by distinct mechanisms or by shared systemic regulators.

Alongside factor discovery, this FOA is explicitly centered on mechanism. Applicants are expected to go beyond descriptive findings and test how candidate factors or cellular responses actually produce rejuvenation-like outcomes in older animals or aging-like outcomes in younger animals. Mechanistic work could include mapping signaling pathways, clarifying receptor-ligand interactions, defining downstream transcriptional programs, and demonstrating causal links using genetic, pharmacologic, or other perturbation strategies in appropriate animal models. The overall theme is to explain how age-related traits are transmitted through the circulation during heterochronic exchange and why those traits manifest differently depending on age, tissue context, and cell state.

Another key anticipated product of funded studies is the development of molecular signatures of rejuvenation or accelerated aging. In practical terms, this means generating measurable biomarker patterns that track with "younger" or "older" functional states after blood exchange, such as transcriptomic, epigenetic, proteomic, metabolomic, or immune profiling signatures. These signatures are expected to help the field standardize what "rejuvenation" or "age acceleration" looks like at a molecular level, support reproducibility across studies, and create tools that can be used to compare interventions or define biological age shifts in experimental systems.

The award mechanism is an R01 research project grant, and the announcement states "Clinical Trial Not Allowed," meaning the supported work is intended to be non-clinical and generally centered on laboratory animals and mechanistic biology rather than interventional studies in human participants. The activity category is Health and the listing is associated with CFDA 93.866. The sponsor is the National Institutes of Health, and the opportunity was posted with a creation date of December 17, 2019, with an original closing date of June 17, 2020. The listed award ceiling is $300,000, indicating an upper bound on funding per award as described in the source details.

Eligibility is broad across U.S.-based organizational types, spanning public and private institutions of higher education, nonprofits (including those with or without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and multiple levels of government (state, county, city/township, special district), as well as independent school districts and public housing authorities/Indian housing authorities. It also includes federally recognized Native American tribal governments and Native American tribal organizations that are not federally recognized. The FOA additionally calls out a range of mission- and community-centered institution types as eligible applicants, including Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), as well as faith-based or community-based organizations and eligible federal agencies. U.S. territories or possessions are also included among eligible applicants.

At the same time, the announcement draws clear boundaries around foreign involvement. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply, and non-domestic components of U.S. organizations are also not eligible. In addition, foreign components, as defined by NIH policy, are not allowed under this FOA. In effect, the funded work must be led and conducted within eligible U.S.-based organizational structures without foreign components as part of the project.

Taken together, this funding opportunity is designed to push the heterochronic blood exchange field from intriguing observations toward a more complete biological explanation. It seeks projects that identify and validate circulating drivers, determine which cells and tissues mediate the effects, and establish mechanistic models that explain how youthful or aged phenotypes can be transferred between animals. By also prioritizing molecular signatures tied to rejuvenation or age acceleration, the FOA signals an interest in producing durable, broadly useful datasets and biomarkers that can anchor future aging biology research and help unify findings across labs.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Mechanisms of Rejuvenation and Age-Acceleration in Heterochronic Blood Exchange (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 2019-12-17.
• Applicants must submit their applications by 2020-06-17. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $300,000.00 in funding.
• 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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