Request for Proposals
NIA seeks proposals for agents to be included in Stage I testing to determine effects on lifespan. Interventions can include, but are not limited to, pharmaceuticals, nutraceuticals, dietary supplements, plant extracts, hormones, peptides, amino acids, chelators, redox agents, and mixtures of compounds. All test agents must be able to be stably incorporated into rodent chow. Applicants can be individuals, nonprofit or academic groups, or commercial entities. NIA is responsible for the costs of the testing through grants to the three testing sites.
The application should be prepared using the Interventions Testing Program (ITP) Application Form (Word, 32K) and submitted as a single Adobe Acrobat® PDF file to Dr. Jennifer Fox (firstname.lastname@example.org). Individuals or groups can propose more than one intervention for consideration, but should use a separate application form for each proposed intervention. Applications that do not conform to this requirement may be returned without review. Although there is no length limit, most applications are between five and 10 pages long.
Applications must include:
- Background and Rationale
Describe concisely the reason why the proposed intervention deserves to be evaluated for potential effects on longevity and aging. Ideally, the rationale should include preliminary data showing the ability of the agent to extend lifespan in mice, prevent disease in mice or humans, or extend lifespan in another model organism. Data showing that the proposed agent affects biochemical or physiological systems thought to be of high relevance to aging biology will also be carefully considered.
If this section includes unpublished data, include enough information (i.e., figures, tables, protocols) to permit its evaluation. If this section includes published data, include similar information and a reference citation to the publication(s) from which the data are derived.
Suggested Treatment Protocol
Provide a detailed description of the proposed intervention and the rationale for the proposed treatment protocol and address the following questions:
Can the substance be given in rodent chow? How stable is the test agent when incorporated into food? Is it stable at room temperature? Should the preparations be protected from light or heat?
What dose should be used?
Please state your recommendation of concentration as parts per million (ppm) in food; this is milligrams of agent per kilogram of food.
Please do not state recommended concentrations or doses as “mpk,” “mg/kg,” or “milligrams per kilogram,” because these formats do not distinguish clearly between concentration versus dose: i.e., “mg/kg of food” [concentration] versus “mg/kg mouse body weight per day” [dose]. Do not state drug dose as mg/kg of body weight per day. Instead, convert the dose into ppm, i.e., milligrams of drug per kilogram of food.
Tip: If a drug is dosed at 1 milligram per kilogram of mouse body weight per day, this is the same as a concentration of 6 ppm in food. A drug used at X milligrams per kilogram of mouse body weight per day is being prepared as 6X ppm in food. This 1:6 conversion factor reflects the ITP assumptions that the average adult mouse weighs 30 grams and consumes 5 grams of food each day.
What is the best way to monitor treated mice to ensure that the intake of the agent produces the expected physiological or pharmacological effects? Will this require blood tests or skin samples, or will it require that some of the mice be sacrificed to obtain internal tissues? If a blood test is required, how much blood is needed? At what age, or at what time after treatment initiation, should the test be performed? How expensive is the test to conduct? If the test requires specialized expertise or equipment, is this available in the sponsor’s laboratory?
Is there a reason to initiate feeding of the intervention at an age other than 4-6 months? If so, at what age should the treatment be initiated? Is there a range of ages that would be acceptable?
- Safety Information
Describe any harmful side effects the treatment might have on mice and humans. State if there are any existing data based on either short-term or long-term exposure of rodents, humans, or other mammals to any dose of the proposed agent or related agents and describe any toxicities noted in the studies. If, for example, there is a published study in which mice were given the drug at a stated dose for a period of weeks or months without ill effects, please provide this information.
Indicate whether the test agent can be obtained commercially, or whether it must be obtained from the applicant. If the drug is available only from the applicant, state whether it can be provided free of charge, or whether the ITP would be expected to pay some or all of the cost. In making this assessment, assume that the ITP will need to prepare 2,100 kg of food over the course of the entire study. If the compound can be purchased commercially, indicate which supplier(s) are recommended and why, and the projected cost of the treatment (in dollars per year of treatment), assuming 2,100 kg of food over the course of the study.
- Applicant/Co-Applicant Biosketch or CV
- Signed Statement of Understanding
The Statement of Understanding can be found on the last page of the ITP Application Form (Word, 32K) and must be signed by all applicants and co-applicants.
Examples of Successful Proposals
Example 1 – MIF098 (PDF, 296 KB)
Example 2 – Resveratrol (PDF, 200 KB)
Example 3 – Sulindac (Word, 178 KB)
Example 4 – mTOR Inhibitors (Word, 227 KB)
Applicants whose proposed interventions are not accepted for testing by the ITP will receive a brief summary of the reviewers’ comments, questions, and concerns. Applicants who are able to fully address these concerns are welcome to resubmit their application for consideration another year. The resubmission should include responses to the comments and questions from the reviews and an explanation of how the application has been modified and strengthened.