Interventions Testing Program (ITP)
NIA's ITP is a multi-institutional study investigating treatments with the potential to extend lifespan and delay disease and dysfunction in mice. Such treatments include:
- Dietary supplements
- Plant extracts
- Amino acids
- Redox agents
- Other agents or mixtures of agents
Priority consideration will be given to the treatments that are easily obtainable, reasonably priced, and can be delivered in the diet (preferred) or water. Interventions that require labor intensive forms of administration, such as daily injections or gavage, are not feasible within the design of the ITP.
Although the testing is performed at the University of Michigan, the Jackson Laboratories, and the University of Texas Health Sciences Center at San Antonio, the project is designed to involve collaborations with investigators at any university, institute, or other organization that has ideas about pharmacological interventions that might decelerate aging and wishes to test these in a lifespan study of mice. An introduction to the logic and rationale for the ITP can be found in Warner, et al. (Mechanisms of Ageing and Development, 115: 199–207, 2000). It is likely that the ITP will accept 3–5 different interventions for testing each year.
The ITP invites scientists to recommend interventions they believe are worth testing. Each intervention has a "sponsor," whose responsibilities include:
- Provide a rationale for the choice of intervention
- Make recommendations about proper dose and timing of the intervention
- Propose methods for documenting the intervention has the expected biochemical and/or physiological effects
- Propose methods to assay the compound in the food and in the mouse serum to ensure the compound is stable and reaches expected blood serum levels
- Identify potential sources of material.
It is imperative that sponsors provide firm recommendations on bullets 2 through 5. The ITP is depending on the involvement of the sponsor, the expert in that particular field, to help finalize the testing protocol. See suggestions for developing interventions proposals that meet the needs of the ITP review process and protocol design.
If the intervention is selected for inclusion in the ITP study, its sponsor will be asked to help analyze the resulting data set and to participate in the preparation of coauthored publications. The testing protocol should provide sufficient statistical power to detect lifespan increases (or decreases) in the 10–15 percent range. In addition, compounds are tested to determine if they have effects on a range of late-life traits, potentially including studies of immune function, hormonal and metabolic profiles, and behavioral outcomes.
Data Publication and Further Investigation
Because a major goal of the project is to provide critical tests of anti-aging approaches, all data are published, including negative results (e.g., a particular agent lacks efficacy or has toxic side effects). In addition, the multisite strategy provides replication for any agent that decelerates aging or inhibits late-life diseases in mice. The multisite strategy would initiate further investigation of the intervention(s) and their congeners. For additional information, see Frequently Asked Questions.
Submission, Deadline, and Review
To propose interventions for testing, use the ITP Application Form for Sponsors of Longevity Intervention Proposals. Submit the completed application as a Word document via email to Dr. Francesca Macchiarini (Francesca.Macchiarini@nih.gov) and include CV or NIH Biosketch. All nominations will be reviewed by the Access Panel and prioritized by the Steering Committee.
Compounds In Testing
Tables of various compounds in testing are available.
Collaborative Interactions Program
The NIA's Intervention Testing Program (ITP) is launching a new Collaborative Interactions Program (CIP) to facilitate research by multiple laboratories on drugs that may retard aspects of aging and increase healthy lifespan in mice.
The Rapamycin Phase II Study
The Rapamycin Phase II Study page describes the goals of the Phase II study on rapamycin, the tissues available for collaborative studies, and the data available for collaborators.
Papers from the Interventions Testing Program
A list of papers resulting from ITP testing is available.
Positive Findings from the ITP
As of Cohort 8, C2012, 6 compounds have shown significant extension of median lifespan:
Aspirin – Increased lifespan in males but not females (Strong et al., 2008).
Rapamycin – Increased mean and maximal lifespan in both males and females when initiated at 20 months of age (Harrison et al., 2009) and when initiated at 9 months of age (Miller et al., 2011). Females responded more robustly than males at equivalent doses; when ~ equal blood levels were achieved, response was also about equivalent in females and males (Miller et al., 2013).
17αEstradiol – Increased lifespan in males but not females, at 4.8 ppm dose (Harrison et al., 2013) and 14.4 ppm dose (Strong et al., 2016).
Acarbose – Increased lifespan in both males and females, but the effects were greater in males, when initiated at 4 months of age (Harrison et al., 2013), but only males responded when initiated at 16 months of age (Strong et al., 2016).
NDGA (nordihydroguaiaretic acid) – Increased mean lifespan in males but not females (Strong et al., 2008), even at doses that gave equivalent blood levels in males and females (Harrison et al., 2013).
Protandim® – Increased lifespan in males but not females (Strong et al., 2016).