The domestic house cricket as a versatile model for functional aging and therapeutic testing

Abstract

Introduction: Aging impairs physiological and cognitive function across species, yet invertebrate models often lack the organ complexity to reflect vertebrate aging. We establish the house cricket (Acheta domesticus) as a scalable, biologically rich model for high-throughput assessment of age-related decline in locomotion, cognition, and behavior. Using defined life stages, we evaluate functional aging and test rapamycin, acarbose, and phenylbutyrate, individually and in combination, for their therapeutic potential.Methods: House crickets were reared under standardized conditions and fed diets containing rapamycin, acarbose, phenylbutyrate, or their combination (SLAM). Animals underwent age-targeted or longitudinal treatment and were evaluated using open field, treadmill, Y-maze, and odor-guided escape assays. Locomotor patterns were classified via k-means clustering and cognitive flexibility was assessed through tetragram analysis. Lifespan was monitored, and post-mortem-tissues were collected for histology. Behavioral and survival outcomes were analyzed using machine learning, parametric/non-parametric tests, and Kaplan-Meier estimates. Analyses were conducted in Python and GraphPad Prism. Results: Across >1,100 crickets, phenylbutyrate, rapamycin, and acarbose extended lifespan (HR’s = 0.50 to 0.61, P’s < 0.05), with strongest effects in females. SLAM conferred early but unsustained survival benefits (HR = 0.37, P < 0.0001). Exploratory strategy and entropy declined with age (adults vs. geriatrics: d = 1.04, P < 0.0001), but were unaffected by treatment (d’s < 0.34, P’s > 0.05). Olfactory discrimination diminished with age, but was rescued by acarbose, rapamycin, and phenylbutyrate (d’s = -1.82 to -1.28, P’s < 0.004), with rapamycin restoring preference in both sexes. Locomotor performance declined with age but improved with treatment. Rapamycin restored distance, speed, and running efficiency to juvenile levels (e.g., total distance: d = -1.09, P = 0.0026). Central exploration deficits were selectively reversed by rapamycin and SLAM (e.g., central time: d = -1.48, P = 0.0001). On treadmill assays, rapamycin, phenylbutyrate, and SLAM restored maximum velocity (d’s = -2.30 to -1.32, P’s < 0.0001) and running time (d’s = -2.30 to -1.32, P’s < 0.0001), whereas acarbose had no effect. Jumping distance declined only in females (d = 1.33, P = 0.0063), with partial rescue by rapamycin and acarbose in a sex-specific manner. In the escape task, aging impaired weight gain, learning, and memory (e.g., adult vs. geriatric task success: RR = 7.20, P < 0.0004). Mid-age crickets showed prolonged decision times and delayed goal-arm arrival (e.g., reward latency: d’s = -1.42 to 1.64, P’s < 0.0001 to 0.014), while geriatric performance was relatively preserved. Conclusion: House crickets demonstrate age-related decline across survival, sensory, locomotor, and cognitive domains, which are attenuated by geroprotective interventions. Rapamycin consistently rescued performance across multiple assays, while acarbose and phenylbutyrate showed selective benefits. These findings establish the house cricket as a robust and tractable invertebrate model for aging research and cross-species drug discovery.