The house cricket (Acheta domesticus) as a scalable invertebrate model for gerotherapeutic testing

TL;DR

House crickets are a promising model for testing drugs that slow aging, with intermittent rapamycin treatment showing strong benefits for survival and behavior.

Contribution

The study introduces the house cricket as a scalable invertebrate model for gerotherapeutic drug testing and evaluates intermittent dosing of geroprotective compounds.

Findings

Intermittent rapamycin treatment preserved survival, cognition, and locomotion in crickets.

Acarbose and phenylbutyrate had selective effects, with acarbose reducing female lifespan despite some locomotor benefits.

Rapamycin-treated males matched or exceeded juvenile locomotor activity, while phenylbutyrate reduced it.

Abstract

The house cricket (Acheta domesticus) is a promising preclinical geroscience model due to its short lifespan, low maintenance, age-associated functional decline, and responsiveness to geroprotective drugs. Continuous dosing with rapamycin, acarbose, and phenylbutyrate extends lifespan; whether intermittent dosing offers similar benefits remains unknown. We tested 274 sex-matched crickets given 2-week intermittent dosing of each drug starting at mid-age (8-weeks), followed by behavioral testing at 10-weeks (geriatric stage). Assays included Y-maze olfactory discrimination, open-field exploration, and treadmill performance. Locomotor gaits were identified by velocity-based K-means clustering (silhouette > 0.5). A subset was monitored for post-treatment survival using Kaplan-Meier analysis. Olfactory preference was preserved by all drugs (d = -1.82 to -1.28, P’s < 0.01), with strongest effects in rapamycin-treated individuals. Rapamycin-treated males matched or exceeded juvenile locomotor activity; phenylbutyrate reduced male activity (d = 1.49, P = 0.049) and acarbose increased walking-to-running ratios (d = -0.75, P = 0.029). Rapamycin increased central exploration and freezing (d = -1.55, P < 0.0001), while acarbose and phenylbutyrate increased peripheral freezing (d = -0.76, P = 0.02). Rapamycin and phenylbutyrate extended maximum running time (d = -2.30 to -1.32, P < 0.0001), with sex-specific jumping gains in rapamycin-treated females and acarbose-treated males. Post-treatment lifespan was prolonged by rapamycin (HR = 0.42, P = 0.0004) and reduced by acarbose in females (HR = 2.92 to 3.03, P’s < 0.05). Intermittent rapamycin preserved survival, cognition, and locomotion, while acarbose and phenylbutyrate produced selective benefits, supporting A. domesticus as a scalable model for geroprotective drug discovery.