Interventions Testing Program (ITP)

The Interventions Testing Program (ITP) is a research initiative focused on identifying treatments that may extend healthy lifespan and delay late-life pathologies in mammals, particularly mice. Funded by the National Institute on Aging (NIA), the ITP operates through cooperative agreement grants to various research institutions.

The ITP was established to address the growing interest in interventions that could delay aging and improve health in later life. It was recognized that rigorous, multi-site testing was necessary to validate potential anti-aging compounds.

Program Overview

The ITP, which began in 2002 with the Data Coordinating Center (DCC) added in 2019, tests potential agents for their effects on aging. This is done via lifespan extension and/or delayed onset/severity of late-life pathologies. The program involves the Jackson Laboratory, the University of Michigan, and the University of Texas Health Science Center at San Antonio for testing, and a DCC at the Jackson Laboratory. The ITP has identified nine agents that significantly increase median lifespan, including acarbose, aspirin, canagliflozin, captopril, glycine, nordihydroguaiaretic acid (NDGA), Protandim®, rapamycin, and 17α-estradiol.

Program Administration

The ITP studies are conducted under the leadership of Drs. David Harrison and Nadia Rosenthal at the Jackson Lab, Richard A. Miller at the University of Michigan, and Randy Strong at the University of Texas Health Science Center at San Antonio. Dr. Molly Bogue at the Jackson Lab is the principal investigator of the DCC. Drs. Tiziana Cogliati and Jennifer Fox from the NIA serve as the program and scientific officers, respectively.

Program Workflow

Application Review

The ITP annually invites proposals from the research community. These proposals undergo a two-tiered review process by the Access Panel and the Steering Committee, assessing scientific merit and feasibility.

Agent Testing

Up to six agents are accepted each year, tested simultaneously under standard operating procedures at the three participating sites. Tests are conducted on genetically heterogeneous UM-HET3 mice, including initial pilot testing, followed by Stage I and Stage II testing, focusing on lifespan, health, pathology, and biochemical mechanisms.

Identified Compounds

Over the years, the Interventions Testing Program (ITP) has made significant discoveries by identifying nine agents that have been shown to increase the median lifespan in their test subjects. These compounds, along with the key references to their discovery, are as follows:

• Acarbose: Identified in multiple studies (Harrison 2014, Strong 2016, Harrison 2019), acarbose has been shown to extend lifespan. It is primarily used in the medical field to treat type 2 diabetes by inhibiting enzymes that digest carbohydrates, thereby reducing glucose absorption.
• Aspirin: Aspirin was found to have lifespan-extending properties as reported in Strong 2008. Commonly known for its use as a pain reliever and anti-inflammatory, its role in longevity research adds a new dimension to its therapeutic potential.
• Canagliflozin: Identified in Miller 2020, canagliflozin is primarily used to treat type 2 diabetes. It works by inhibiting the sodium-glucose transport protein, which helps to reduce blood sugar levels.
• Captopril: Discovered to increase lifespan in Strong 2022, captopril is typically employed as a treatment for hypertension and certain types of heart failure.
• Glycine: This simple amino acid was shown to have life-extending effects in Miller 2019. Glycine has various roles in the body, including as a neurotransmitter and a building block for proteins.
• Nordihydroguaiaretic Acid (NDGA): NDGA's impact on lifespan was reported in Strong 2008 and Strong 2016. It is a plant-derived compound known for its antioxidant properties.
• Protandim®: This patented dietary supplement was indicated to increase lifespan in Strong 2016. It is composed of a blend of herbal ingredients and is marketed for its antioxidant benefits.
• Rapamycin: One of the most significant findings of the ITP, rapamycin has been consistently identified in multiple studies (Harrison 2009, Miller 2011, Wilkinson 2012, Miller 2014) as a compound that extends lifespan. Originally developed as an immunosuppressant, rapamycin has gained attention for its potential anti-aging properties.
• 17α-Estradiol: Found to increase lifespan in Harrison 2014, Strong 2016, and Harrison 2021, 17α-Estradiol is a stereoisomer of the hormone estradiol and has shown promise in age-related research.

Each of these compounds has contributed to our understanding of aging and longevity, providing valuable insights into potential therapeutic approaches for extending healthy life.

See Also

• National Institute on Aging - Interventions Testing Program
• Lifespan Extending Compounds in Model Organism
• 2022-04-12 - Dr. Richard Miller - Longevity Supplements - Interventions Testing Program Results
• Interview of Prof. Richard Miller on the Intervention Testing Program (May 5, 2022)