An Aging Interventions Testing Program: study design and interim report

Area of Science:

• Gerontology and aging research
• Drug discovery and development for aging interventions

Background:

• The National Institute on Aging's Interventions Testing Program (ITP) aims to identify agents that delay aging.
• Genetically heterogeneous mice are used to model aging processes.
• Multi-site replication ensures study robustness.

Purpose of the Study:

• To evaluate the efficacy of four agents (aspirin, nitroflurbiprofen, 4-OH-PBN, and NDGA) in delaying aging rates.
• To assess the impact of these agents on lifespan and age-dependent physiological changes.

Main Methods:

• Utilized a standardized four-way cross of genetically heterogeneous mice across three test sites.
• Administered aspirin, nitroflurbiprofen (NFP), 4-OH-alpha-phenyl-N-tert-butyl nitrone (4-OH-PBN), or nordihydroguiaretic acid (NDGA) to mice.
• Conducted interim survival analysis based on median lifespan.

Main Results:

• Nordihydroguiaretic acid (NDGA) significantly improved male mouse survival (P = 0.0004) across multiple sites.
• No significant lifespan alterations were observed for aspirin, NFP, or 4-OH-PBN.
• Aspirin showed a non-significant trend towards improved male survival (P = 0.07).

Conclusions:

• NDGA demonstrates potential in reducing early mortality in genetically heterogeneous mice.
• Further research is required to confirm if these agents can extend maximal lifespan.
• The ITP provides a robust platform for evaluating aging intervention candidates.