A composite frailty index enables quantification of functional aging and identification of gerotherapeutic drugs in the house cricket

Abstract

Frailty is increasingly recognized as a clinically relevant measure of biological aging, yet comparable assessment tools are lacking for scalable invertebrate models. Here, we introduce a Composite Frailty Index (CFI) for the house cricket ( Acheta domesticus ) integrating automated measures of locomotion, exploration, and freezing into a quantitative framework of functional decline. Ten behavioral parameters from automated open-field tracking were normalized to age- or treatment-matched reference populations, discretized into quintiles, and combined to generate a 0–1 frailty score. Aging cohorts (young adult: 4–6 weeks; older adult: 10–12 weeks, N = 103) and mid-life (8-10 weeks) pharmacological cohorts treated with rapamycin (14 ppm), acarbose (1000 ppm), or phenylbutyrate (1000 ppm) ( N = 122) were evaluated. CFI increased with age in both sexes ( d ’s = −1.17 to −1.14; P ’s < 0.001). Rapamycin reduced late-life frailty in both sexes ( d = −1.33 to −1.31; P ’s < 0.01), whereas acarbose and phenylbutyrate produced inconclusive effects ( d ’s = −0.54 to −0.03; P ’s > 0.05). These findings establish the cricket CFI as a scalable, high-throughput platform for quantifying functional aging and evaluating candidate geroprotective interventions beyond lifespan.