Elucidating Variability of Physiologic and Functional Responses to Exercise Training in Older Adults (R01 Clinical Trial Required) | RFA AG 24 045

Opportunity Information: Apply for RFA AG 24 045

The National Institutes of Health (NIH) funding opportunity titled "Elucidating Variability of Physiologic and Functional Responses to Exercise Training in Older Adults (R01 Clinical Trial Required)" (Funding Opportunity Number: RFA-AG-24-045) supports human subject research aimed at explaining why older adults respond so differently to the same exercise training programs. The central theme is response variability: some people show meaningful gains in physical function and physiology with training, while others improve only modestly or in different ways. This NOFO is looking for rigorous clinical trials that move beyond showing that exercise works on average and instead dig into the biological, behavioral, and environmental reasons outcomes vary from person to person in later life.

The NOFO specifically encourages projects that identify systemic modulators and measurable indicators of response differences, such as biomarkers and other plausible mechanisms that could explain who benefits, how, and under what conditions. The endpoints of interest should be clinically relevant for older adults, meaning outcomes tied to health and independence rather than purely laboratory measures. While the announcement does not list specific endpoints in the excerpt provided, the intent clearly points toward measures that reflect real-world function and physiology in aging, such as mobility, strength, endurance, cardiometabolic function, and other markers that could translate into improved quality of life, reduced disability, or better resilience.

A major emphasis is on transdisciplinary, mechanism-oriented work that combines innovative study designs and advanced analytic approaches with deep clinical phenotyping. In practice, that means NIH is signaling interest in studies that capture detailed participant characteristics (phenotypes) and use modern methods to untangle complex cause-and-effect relationships. The NOFO highlights the interplay of endogenous and exogenous factors driving variation in exercise response. Endogenous factors generally include internal characteristics such as genetics, underlying physiology, inflammatory or metabolic status, comorbidities, medication use, and baseline functional capacity. Exogenous factors generally include external influences such as diet, sleep, psychosocial stress, neighborhood and built environment, access to resources, prior physical activity exposure, and adherence supports. The goal is not only to map these influences, but also to determine which factors are modifiable so they can be targeted to make exercise prescriptions more precise and more effective for older adults.

The long-term payoff NIH is aiming for is practical: if researchers can clarify why responses vary and identify actionable drivers of that variability, clinicians and public health practitioners could tailor exercise prescriptions with greater precision. Instead of a one-size-fits-all training plan, the field could move toward matching the type, intensity, volume, and progression of exercise to an individual older adult's biology, circumstances, and risks, improving the likelihood of meaningful benefits while reducing trial-and-error and potentially avoiding adverse responses.

This opportunity uses the NIH R01 grant mechanism and explicitly requires a clinical trial, meaning applicants are expected to prospectively assign human participants to an intervention (in this case, exercise training and potentially comparative conditions) and evaluate health-related outcomes. The funding instrument type is a grant, and the activity category is health. The CFDA number listed is 93.866, which is associated with NIH aging-related programs. The award ceiling is $1,000,000, indicating the maximum award amount expected under this announcement. The original closing date provided is 2023-11-03, and the opportunity was created on 2023-08-09.

Eligibility is broad and includes many types of organizations: state, county, city/township, and 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 tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (excluding institutions of higher education in those categories); for-profit organizations other than small businesses; small businesses; and other entities. The NOFO also explicitly calls out additional 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-domestic (non-U.S.) entities (foreign organizations). This wide eligibility aligns with the real-world nature of exercise research in older populations, where community settings, diverse participant recruitment, and multidisciplinary partnerships often matter as much as laboratory capacity.

In short, this NIH NOFO is focused on clinical trials in older adults that explain heterogeneity in exercise training outcomes by identifying systemic modulators, biomarkers, and mechanisms, and by using innovative, transdisciplinary approaches to model how internal biology and external context interact. The intended impact is to enable more individualized and clinically effective exercise prescriptions that better support healthy aging and functional independence.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Elucidating Variability of Physiologic and Functional Responses to Exercise Training in Older Adults (R01 Clinical Trial Required)" 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 2023-08-09.
• Applicants must submit their applications by 2023-11-03. (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 $1,000,000.00 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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