Short-Term Performance Assay Identifies Functional Benefits and Early Toxicity of Longevity Interventions in Mice
Abstract
ABSTRACT: Mouse lifespan studies are slow and costly, limiting the number of interventions that have demonstrated robust anti-aging effects. This highlights the need for rapid early-stage screening tools capable of assessing both efficacy and potential side effects. Here, we present a short-term performance assay designed to rapidly profile functional benefits and early toxicity of longevity interventions in mice. Over an 8-week period, mice received one of five candidate anti-aging treatments: 17α-estradiol, rapamycin + Smer28, berberine + resveratrol, sildenafil and pinealon. The protocol longitudinally monitored body weight and temperature, and food intake, alongside post-treatment assessments of grip strength, locomotor activity, Y-maze cognition, social behavior, and hematological and urinary parameters. The screen revealed compound-specific phenotypes: 17α-estradiol induced significant weight loss, increased grip strength, and dorsal alopecia, consistent with metabolic remodeling. Sildenafil reduced basal body temperature and preserved locomotor activity. Berberine + resveratrol decreased food intake and fasting glucose without major changes in physical performance, resembling caloric restriction-like metabolic effects. Rapamycin + Smer28 modestly improved strength and sociability but induced anemia in 2 of 5 mice, indicating potential dose-dependent toxicity. Pinealon showed a trend toward improved working memory without detectable adverse effects. This…
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